The purpose of this study is to investigate the usefulness of PET/MRI with an investigational radioactive drug, 18F-rhPSMA-7.3, and MRI contrast in evaluating patients with prostate cancer eligible for active surveillance. This study is for imaging purposes only and is not a treatment study.

Start Date30 Apr 2025

Sponsor / Collaborator

The University of Alabama at Birmingham

NCT06389786 / RecruitingNot Applicable

Safe Omission of Pelvic Lymph Node Dissection (SOuND) During Radical Prostatectomy: Diagnostic Accuracy of rhPSMA-7.3(18F) PET/CT, mpMRI and Patient Clinical Factors to Predict Lymph Node Metastasis

This clinical trial evaluates the use of an imaging scan (18F-rhPSMA-7.3 positron emission tomography [PET]/magnetic resonance imaging [MRI]) for identifying patients who are at risk of having their disease spread to the lymph nodes in those undergoing radical prostatectomy for prostate cancer that has not spread to other parts of the body (localized). Prostate specific membrane antigen (PSMA) PET/computed tomography (CT) has emerged as an option to stage newly diagnosed high risk prostate cancer patients. PSMA PET/CT has demonstrated improved diagnostic accuracy for identifying metastasis. PET is procedure in which a small amount of radioactive glucose (sugar) is injected into a vein, and a scanner is used to make detailed, computerized pictures of areas inside the body where the glucose is used. Because cancer cells often use more glucose than normal cells, the pictures can be used to find cancer cells in the body. MRI is procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and diseased tissue. This study may help researchers learn whether 18F-rhPSMA-7.3 PET/ MRI may improve predicting which patients are at risk of lymph node metastases and who are suitable candidates for pelvic lymph node dissection in patients with localized high-risk prostate cancer undergoing radical prostatectomy.

Start Date11 Jun 2024

Sponsor / Collaborator

Mayo Clinic

NCT06105918 / RecruitingPhase 1IIT

Phase 1 Trial to Determine Safety and Feasibility in Treating Biochemical Recurrence Post-Prostatectomy With PSMA PET Guided External Beam Radiotherapy Followed by Consolidative Radioligand Therapy

This phase I trial tests the safety, side effects and best dose of radioligand therapy (lutetium Lu 177 PSMA-10.1 [177Lu-rhPSMA-10.1]) after prostate specific membrane antigen (PSMA) positron emission tomography (PET)-guided external beam radiotherapy in treating post-prostatectomy patients with prostate cancer that has come back after a period of improvement (recurrent). In this study, radioligand therapy is a radioactive drug called 177Lu-rhPSMA-10.1. It works by binding to PSMA-expressing prostate tumor cells and delivering the radioactive portion of the drug directly to the tumor cells while not harming normal cells. Radiation therapy such as external beam radiotherapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radioligand therapy with PSMA PET-guided external beam radiotherapy may kill more tumor cells in post-prostatectomy patients with biochemically recurrent prostate cancer.

Start Date29 Nov 2023

Sponsor / Collaborator

Emory University

[+1]

100 Clinical Results associated with Flotufolastat F-18

100 Translational Medicine associated with Flotufolastat F-18

100 Patents (Medical) associated with Flotufolastat F-18

Literatures (Medical) associated with Flotufolastat F-18

01 Feb 2024·Molecular imaging and biology

Quantitative and Qualitative Assessment of Urinary Activity of 18F-Flotufolastat-PET/CT in Patients with Prostate Cancer: a Post Hoc Analysis of the LIGHTHOUSE and SPOTLIGHT Studies

Article

Author: Postema, Ernst J ; Hermsen, Rick ; Penny, Ross ; Kuo, Phillip H

Abstract:

Purpose:

To evaluate the impact of urinary activity on interpretation of 18F-flotufolastat (18F-rhPSMA-7.3) PET/CT, we conducted a post hoc qualitative and quantitative analysis of scans acquired in two phase 3 studies of 18F-flotufolastat.

Procedures:

Newly diagnosed or recurrent prostate cancer patients enrolled in LIGHTHOUSE (NCT04186819) or SPOTLIGHT (NCT04186845), respectively, underwent PET/CT 50–70 min after intravenous administration of 296 MBq 18F-flotufolastat. For the present analysis, 718 18F-flotufolastat scans (352 from LIGHTHOUSE and 366 from SPOTLIGHT) were re-evaluated by three board-certified nuclear medicine physicians. Reader 1 performed a quantitative assessment (SUVmax and SUVmean) of bladder activity in a circular region-of-interest over the maximum diameter of bladder activity in the transverse plane. All three readers qualitatively assessed the impact of any urinary activity in the bladder on image interpretation using a three-point scale (0 = no/minimal visible urinary activity, 1 = urinary activity visible but distinction between urine and disease possible and 2 = assessment inhibited by urinary activity) and the presence/absence of ureteric activity and halo artifacts.

Results:

In total, 712/718 scans were evaluable. Reasons for exclusion were cystectomy, renal failure, or urinary catheter in situ (n = 2 each). The median bladder SUVmax and SUVmean were 17.1 and 12.5, respectively. By majority read, 682/712 (96%) patients had either no urinary activity (score = 0) or visible activity that could be distinguished from disease uptake (score = 1). In the minority of patients (24, 3.4%) where urinary activity did impact assessment (score = 2), the median bladder SUVmean was higher (20.5) than those scored 0 (3.8) or 1 (14.0). Ureteric activity was absent in 401 (56%) patients. Halo artifacts were observed in only two (0.3%) patients (majority read).

Conclusions:

18F-Flotufolastat urinary activity did not influence disease assessment for the majority of patients. While this study was not designed as a head-to-head comparison, the median bladder SUVs are lower than previously reported values for other renally cleared PSMA-PET radiopharmaceuticals.

01 Feb 2024·PharmacoEconomics

Cost-Effectiveness Modeling of Prostate-Specific Membrane Antigen Positron Emission Tomography with Piflufolastat F 18 for the Initial Diagnosis of Patients with Prostate Cancer in the United States

Article

Author: Kirson, Noam Y ; Harvey, Michael J ; Yee, Christopher W ; Xin, Yiqiao

BACKGROUND AND OBJECTIVES:

Piflufolastat F 18 is a novel prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) radiotracer that is superior to standard of care (SOC) imaging for the initial staging of prostate cancer and the detection of biochemical recurrence. As piflufolastat F 18 has been approved in the United States (US) for this indication, this modeling study assessed the cost effectiveness of piflufolastat F 18 versus fluciclovine F-18, gallium68-PSMA-11 (PSMA 11), and SOC imaging (a mix of bone scans, computed tomography, and magnetic resonance imaging) for the diagnosis and staging of prostate cancer from a US healthcare system perspective.

PERSPECTIVE:

A US third-party payer perspective was used, which for this population reflects a mix of commercial and Medicare, considering only direct healthcare costs.

SETTING:

This study utilized a tertiary healthcare setting.

METHODS:

A decision tree was used to map the diagnostic/treatment pathway, consisting of the proportion of patients with local, regional, distant, or no disease; prostate-specific antigen (PSA) ≤ 1.0 or > 1.0; and accuracy of imaging modalities. A Markov model predicted the long-term outcomes of disease progression according to treatment decisions. Inputs to the model were informed by data from the OSPREY and CONDOR clinical trials, public data, and the literature. Treatment mix included active surveillance, radiation therapy, prostatectomy, androgen deprivation therapy (ADT), and radiation therapy + ADT, informed by expert opinion. Outcomes included life-years (LY), quality-adjusted life-years (QALY), and the incremental cost-effectiveness ratio (ICER). All costs were reported in 2021 US dollars, using the US Bureau of Labor Statistics Consumer Price Index. A willingness-to-pay (WTP) threshold of $150,000 was considered cost effective, consistent with the upper range used as the standard for price benchmarks by the Institute for Clinical and Economic Review. The robustness of the base-case results was assessed in deterministic and probabilistic sensitivity analyses.

RESULTS:

Over a lifetime horizon, piflufolastat F 18 had the greatest effectiveness in terms of LYs (6.80) and QALYs (5.33); for the comparators, LYs ranged from 6.58 (SOC) to 6.76 (PSMA 11) and QALYs ranged from 5.12 (SOC) and 5.30 (PSMA 11). Piflufolastat F 18 was more cost effective compared with fluciclovine F 18, PSMA 11, and SOC, with ICERs of $21,122, $55,836, and $124,330 per QALY gained, respectively. Piflufolastat F 18 was associated with the greatest net monetary benefit ($627,918) compared with the other options at a WTP threshold of $150,000. The results of the deterministic and probabilistic sensitivity analyses supported the robustness of the base-case results.

CONCLUSIONS:

This study suggests that piflufolastat F 18 is a cost-effective diagnostic option for men with prostate cancer in the US, with higher associated LY, QALY, and greater net monetary benefit than fluciclovine F 18, PSMA 11, and SOC imaging.

01 Oct 2023·International journal of radiation oncology, biology, physics

Clinicopathologic Features of Prostate Cancer with Mesorectal Lymph Node Involvement on PSMA or Fluciclovine PET/CT.

Article

Author: Gutschenritter, T ; Barbour, A B ; Chen, D L ; Iravani, A ; Gulhane, A ; Chen, J ; Liao, J J ; Weg, E S

PURPOSE/OBJECTIVE(S):

Advanced PET imaging has shown more prevalent mesorectal lymph node (LN) involvement in prostate cancer than previously appreciated. The clinical features predicting risk for mesorectal involvement are not well established and the prognostic impact is unclear. This may have implications on management including radiotherapy field design. This study aims to identify clinical and pathologic characteristics associated with mesorectal involvement identified on PSMA or fluciclovine PET/CT.

MATERIALS/METHODS:

We conducted a single institution retrospective review of prostate cancer patients with F-18 fluciclovine, F-18 piflufolastat, or Ga-68 gozetotide PET between January 2020 and 2023 demonstrating tracer-avid mesorectal LN in the setting of newly diagnosed disease (ND) or biochemical failure after curative-intent therapy (BF). Clinical characteristics, pathologic findings, and early clinical outcomes were reviewed.

RESULTS:

We identified 16 ND and 34 BF patients with uptake in at least one mesorectal LN on PET. For ND patients, clinical features at initial diagnosis were median PSA of 35.2 (range 9.6-659), median grade group 5, and 87% with clinical or radiographic T3/T4 disease. Radiographic PET staging among ND patients (excluding mesorectal LNs) were 19% N0M0, 25% N1M0, 56% as N1M1. For BF patients, clinical features at initial diagnosis were median PSA 9.2 (range 4.1-90) and median grade group 4. Primary treatment was prostatectomy in most (91%), with a high rate of high-risk features: 68% pT3-4, 28% pN1, and 32% had persistent detectable postop PSA. Radiographic PET staging among BF patients (excluding mesorectal LNs) were 29% N0M0, 38% N1M0, 12% N0M1, and 21% as N1M1. High-risk histologic features (cribriform, intraductal, ductal, or neuroendocrine) were identified in 88% of ND and 48% BF patients. Of these patients, 86% had cribriform pattern. Median PSA prior to PET for ND and BF patients was 37.0 (range 8.5-659) and 1.9 (0.2-11.1). Median interval from initial therapy to PET for BF patients was 4.4yr (range 0.2-19.7). Median follow-up post-PET was 8.7mo (range 3.4-29) for ND and 8.8mo (range 0-76) for BF patients. Of patients with M0 PET staging, none of the 7 ND patients developed DMs, and 1 of 23 BF patients developed DM after 4 yrs.

CONCLUSION:

In this analysis of prostate cancer patients with mesorectal involvement, we found a high incidence of high grade, T3-4 disease, and cribriform pattern, especially in ND patients. For BF patients, there was a high incidence of pT3-4 and pN1 disease at time of initial treatment. Overall, most patients had concurrent regional nodal disease on PET. Longer follow up of clinical outcomes and comparison to high-risk patients without mesorectal LN involvement is needed to understand the prognostic significance and predictors of mesorectal LN spread. Additional studies are needed to identify patients at highest risk in whom elective coverage of mesorectal lymphatics with elective pelvic nodal RT may be warranted.

News (Medical) associated with Flotufolastat F-18

10 Jun 2024

·www.biospace.com

Blue Earth Diagnostics Highlights Results of Studies Evaluating Impact of Urinary Activity on Image Interpretation and Performance of POSLUMA® (Flotufolastat F 18) and 18F-Flotufolastat PET in Prostate Cancer

MONROE TOWNSHIP, N.J. & OXFORD, England--(BUSINESS WIRE)-- Blue Earth Diagnostics, a Bracco company and recognized leader in the development and commercialization of innovative PET radiopharmaceuticals, today announced highlights from clinical studies conducted by its collaborators at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, June 8-11, 2024. They included interim results of a study by Emory University that evaluated POSLUMA® (flotufolastat F 18) injection PET/CT with and without furosemide in men with biochemically recurrent prostate cancer (BCR), as well as results of a retrospective study conducted by the Technical University of Munich (TUM) that evaluated qualitative and quantitative PET parameters in urinary activity and tumor uptake for 18F-flotufolastat and 68Ga-PSMA-11 in primary prostate cancer. The studies build upon a recently published post-hoc analysis of Blue Earth Diagnostics’ clinical studies in which POSLUMA demonstrated low urinary bladder interference that did not impact disease assessment in the vast majority of patients1. Links to the abstracts follow below. POSLUMA is approved and indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. 18F-Flotufolastat produced at TUM is an investigational agent for which the safety and efficacy have not been established by the U.S. Food and Drug Administration. “The ability to gather actionable information from PSMA PET scans is important for physicians to make informed decisions about patient management for men with prostate cancer,” said Eugene Teoh, MBBS, MRCP, FRCR, D.Phil., Chief Medical Officer of Blue Earth Diagnostics. “Activity in the urinary tract, especially in the urinary bladder, is a common feature of FDA-approved PSMA-PET radiopharmaceuticals which are excreted via the urine. High urinary activity can potentially obscure tumors in the prostate region and regional lymph nodes in the pelvis, which are common sites of recurrence, and interfere with accurate image interpretation.” Dr. Teoh continued, “These results reported at SNMMI support our previous experience with POSLUMA and are broadly consistent with results from our clinical trials. A post-hoc analysis of our Phase 3 clinical trials demonstrated that 96% of patients (682/712) exhibited either no urinary activity or activity that was easily distinguishable from disease1. Although furosemide usage has been widely described for other PSMA PET imaging agents as a potential means to reduce urinary activity, the POSLUMA Phase 3 trial results were achieved without its use. In cases from this Emory study where furosemide was not used, results also demonstrate the high POSLUMA detection rates in patients with low PSA levels as observed in prior Blue Earth Diagnostics clinical trials.” “These findings from Emory and TUM reinforce important clinical considerations in selecting a precision diagnostic imaging agent for PSMA-PET procedures,” said David E. Gauden, D.Phil., Chief Executive Officer of Blue Earth Diagnostics. “POSLUMA provides physicians with useful information based on its performance at low PSA levels, PSMA binding and low urinary bladder activity. It is included in nationally recognized clinical oncology guidelines for prostate cancer and covered by the vast majority of insurance plans. Labeled with the radioisotope fluorine-18 (18F) to leverage high image quality, POSLUMA is widely available through the network of our commercial U.S. manufacturer and distributor, PETNET Solutions Inc, A Siemens Healthineers Company.” Highlights of the Abstracts Impact of forced diuresis with furosemide in the evaluation of biochemical recurrence of prostate cancer with 18F-rhPSMA 7.3 PET/CT: Interim analysis of an ongoing prospective trial Interim results from a prospective study were presented by Ismaheel Lawal, MD, PhD, Resident Physician, Department of Radiology and Imaging Sciences, Emory University, Atlanta Ga. The study investigated the impact of forced diuresis with furosemide during 18F-flotufolastat PET/CT imaging for further improved bladder activity and prostate bed region recurrence detection in BCR. Twelve men had completed both with- and without-furosemide PET/CT scans at the time of the interim analysis. The study assessed bladder activity by SUV, patient-level recurrence and recurrence in the prostate-bed region. The authors concluded that furosemide-augmented bladder activity reduction showed no safety issues and was feasible for 18F-flotufolastat PET/CT imaging. While recognizing detection rates without furosemide remain high and consistent with Phase 3 studies, recurrence detection may be enhanced with the use of furosemide, by further decreasing observed urinary activity, and with no impact on the radiotracer avidity in the recurrent lesion. The full abstract is available here. Evaluation of qualitative and quantitative PET parameters in primary prostate cancer patients: double-match comparison of 18F-flotufolastat- and 68Ga-PSMA-11-PET Results from a retrospective study were presented by Isabel Rauscher, MD, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Markt Schwaben, Germany. The study evaluated qualitative and quantitative PET parameters in urinary activity and tumor uptake for 18F-flotufolastat and 68Ga-PSMA-11 in a matched cohort of 62 patients staged for primary prostate cancer. Parameters included overall interference from bladder activity, scoring of median semi-quantitative bladder activity, presence of ureteral retention and halo artifacts, and tumor-to-bladder uptake ratio. The authors concluded that interpretation of 68Ga-PSMA-11 PET was significantly more impacted by bladder activity than 18F-flotufolastat PET in the matched populations of primary prostate cancer patients. The full abstract is available here. Indication and Important Safety Information About POSLUMA INDICATION POSLUMA® (flotufolastat F 18) injection is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level IMPORTANT SAFETY INFORMATION Image interpretation errors can occur with POSLUMA PET. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of POSLUMA for imaging metastatic pelvic lymph nodes in patients prior to initial definitive therapy seems to be affected by serum PSA levels and risk grouping. The performance of POSLUMA for imaging patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels. Flotufolastat F 18 uptake is not specific for prostate cancer and may occur in other types of cancer, in non-malignant processes, and in normal tissues. Clinical correlation, which may include histopathological evaluation, is recommended. Risk of Image Misinterpretation in Patients with Suspected Prostate Cancer Recurrence: The interpretation of POSLUMA PET may differ depending on imaging readers, particularly in the prostate/prostate bed region. Because of the associated risk of false positive interpretation, consider multidisciplinary consultation and histopathological confirmation when clinical decision-making hinges on flotufolastat F 18 uptake only in the prostate/prostate bed region or only on uptake interpreted as borderline. POSLUMA use contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Advise patients to hydrate before and after administration and to void frequently after administration. Ensure safe handling to minimize radiation exposure to the patient and health care providers. The adverse reactions reported in ≥0.4% of patients in clinical studies were diarrhea, blood pressure increase and injection site pain. Drug Interactions: androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F 18 in prostate cancer. The effect of these therapies on performance of POSLUMA PET has not been established. To report suspected adverse reactions to POSLUMA, call 1-844-POSLUMA (1-844-767-5862) or contact FDA at 1-800-FDA-1088 or . Full POSLUMA prescribing information is available at . About Blue Earth Diagnostics Blue Earth Diagnostics, an indirect subsidiary of Bracco Imaging S.p.A., is a growing international molecular imaging company focused on delivering innovative, well-differentiated diagnostic solutions that inform patient care. Formed in 2014, the Company’s success is driven by its management expertise and supported by a demonstrated track record of rapid development and commercialization of positron emission tomography (PET) radiopharmaceuticals. Blue Earth Diagnostics’ expanding oncology portfolio encompasses a variety of disease states, including prostate cancer and neuro-oncology. Blue Earth Diagnostics is committed to the timely development and commercialization of precision radiopharmaceuticals for potential use in imaging and therapy. For more information, please visit: . About Bracco Imaging Bracco Imaging S.p.A., part of the Bracco Group, is a world-leading diagnostic imaging provider. Headquartered in Milan, Italy, Bracco Imaging develops, manufactures and markets diagnostic imaging agents and solutions. It offers a product and solution portfolio for all key diagnostic imaging modalities: X-ray imaging (including Computed Tomography-CT, Interventional Radiology, and Cardiac Catheterization), Magnetic Resonance Imaging (MRI), Contrast Enhanced Ultrasound (CEUS), and Nuclear Medicine through radioactive tracers and novel PET imaging agents to inform clinical management and guide care for cancer patients in areas of unmet medical need. Our continually evolving portfolio is completed by a range of medical devices, advanced administration systems and dose-management software. In 2019 Bracco Imaging enriched its product portfolio by expanding the range of oncology nuclear imaging solutions in the urology segment and other specialties with the acquisition of Blue Earth Diagnostics. In 2021, Bracco Imaging established Blue Earth Therapeutics as a separate, cutting-edge biotechnology vehicle to develop radiopharmaceutical therapies. Visit: . 1Kuo PH, Hermsen R, Penny R, Postem EJ. Post-hoc analysis of the LIGHTHOUSE and SPOTLIGHT studies to assess the impact of urinary activity on interpretation of 18F-rhPSMA-7.3 PET/CT. Mol Imaging Biol. 2024 Feb;26(1):53-60. doi: 10.1007/s11307-023-01867-w. POSLUMA is a registered trademark of Blue Earth Diagnostics Ltd. PP-rh-US-0499 This press release is for U.S. audiences only View source version on businesswire.com: Contacts For Blue Earth Diagnostics (U.S.) Priscilla Harlan Vice President, Corporate Communications (M) (781) 799-7917 priscilla.harlan@blueearthdx.com For Blue Earth Diagnostics (UK) Clare Gidley Associate Director Marketing and Communications Tel: +44 (0) 7917 536939 clare.gidley@blueearthdx.com Media Mike Beyer (M) (312) 961-2502 mikebeyer@sambrown.com Source: Blue Earth Diagnostics View this news release online at:

Clinical ResultPhase 3

29 May 2024

·www.biospace.com

Blue Earth Diagnostics Highlights Presentations on POSLUMA®

MONROE TOWNSHIP, N.J. & OXFORD, England--(BUSINESS WIRE)-- Blue Earth Diagnostics, a Bracco company and recognized leader in the development and commercialization of innovative PET radiopharmaceuticals, today announced upcoming presentations by its collaborators at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, to be held June 8 to 11, 2024, in Toronto, Canada. POSLUMA® (formerly referred to as 18F-rhPSMA-7.3) is approved and indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. Axumin® is approved and indicated for PET imaging in men with suspected prostate cancer recurrence based on elevated PSA levels following prior treatment. “We are pleased that our collaborators will be sharing important scientific information about POSLUMA, Axumin and investigational experience with 18F-flotufolastat with the imaging community at SNMMI,” said David E. Gauden, D.Phil., Chief Executive Officer of Blue Earth Diagnostics. “Two presentations relate to the use of POSLUMA and 18F-flotufolastat and the effects of urinary bladder activity on imaging quality. Results from a head-to-head study to be presented by Dr. Isabel Rauscher of the Technical University of Munich examine parameters of PET imaging between 18F-flotufolastat and 68Ga-PSMA-11 in primary prostate cancer, and a presentation by Dr. Ismaheel Lawal will discuss interim results from a study at Emory assessing PET imaging quality with and without the diuretic furosemide in patients with biochemical recurrence of prostate cancer (BCR). Dr. Nadine Mallak of Oregon Health and Science University will present interim results from an ongoing study of the use of Axumin in PSMA/PET-negative BCR patients, and Dr. Rauscher will also describe clinical experience with 18F-rhPSMA-7 and 18F-flotufolastat PET in salvage therapy planning for BCR.” Details of selected oral and poster presentations by Blue Earth Diagnostics collaborators are listed below. Presentations noted by “*” discuss results of experiences with an investigational agent for which the safety and efficacy have not been established by the FDA. POSLUMA (flotufolastat F 18), investigational 18F-flotufolastat and 18F-rhPSMA-7 DATE: Sunday, June 9, 2024 Title: Impact of forced diuresis with furosemide in the evaluation of biochemical recurrence of prostate cancer with 18F-rhPSMA 7.3 PET/CT: Interim analysis of an ongoing prospective trial Presenter: Ismaheel Lawal, MD, PhD, Resident Physician, Department of Radiology and Imaging Sciences, Emory University, Atlanta Ga. Session Title: MTA05 POPs/Meet the Author: Oncology: Clinical Therapy & Diagnosis 1 Session Type: Poster presentation Session Time: 5:00 – 6:15 PM ET Abstract ID.: 241368 DATE: Sunday, June 9, 2024 Title: *Evaluation of qualitative and quantitative PET parameters in primary prostate cancer patients: double-match comparison of 18F-flotufolastat and 68Ga-PSMA-11-PET Presenter: Isabel Rauscher, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Markt Schwaben, Germany Session Title: MTA05 POPs/Meet the Author: Oncology: Clinical Therapy & Diagnosis 1 Session Type: Poster presentation Session Time: 5:00 – 6:15 PM ET Abstract ID.: 241424 DATE: Saturday, June 8, 2024 Title: *18F-rhPSMA-7 and 18F-flotufolastat PET-guided salvage radiotherapy in recurrent prostate cancer Presenter: Isabel Rauscher, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Markt Schwaben, Germany Session Title: Prostate Cancer: Focus on Imaging Session Type: Oral presentation Session Time: 3:30 – 4:45 PM ET Presentation: 3:35 – 3:45 PM ET Abstract ID.: 241112 Axumin (fluciclovine F 18) DATE: Sunday, June 9, 2024 Title: Role of 18F-fluciclovine PET/CT in patients with biochemical recurrence of prostate cancer and a negative PSMA PET/CT: interim results from a prospective trial Presenter: Nadine Mallak, MD, Associate Professor, Department of Diagnostic Radiology | Molecular Imaging & Therapy, Body Imaging Director, PET/MRI, Clinical, Oregon Health and Science University, Portland, Ore. Session Title: MTA05 POPs/Meet the Author: Oncology: Clinical Therapy & Diagnosis 1 Session Type: Poster presentation Session Time: 5:00 – 6:15 PM ET Abstract ID.: 241835 Blue Earth Diagnostics invites participants at the 2024 SNMMI Annual Meeting to attend the presentations above and to visit the Company at Exhibit Booth 1639. The Company is hosting a Satellite Symposium, “Let’s Talk about POSLUMA®,” which will discuss the most recent innovations in PSMA-PET imaging for prostate cancer. It will feature invited speakers Sean Collins, MD, PhD, Professor, Georgetown University Hospital, and Elizabeth Hawk, MD, PhD, DABNM DABR, University of California San Diego, and be moderated by Todd Cohen, MD, VP of Medical Affairs, Blue Earth Diagnostics, Inc. The symposium will be held on Sunday, June 9, 2024, from 11:15 AM – 12:15 PM ET in the Toronto Convention Center, Room 701A, South Building – 700 Level. Blue Earth Diagnostics also has a Medical Affairs information booth at SNMMI, where attendees can learn about the Company’s clinical research. For full session details and scientific presentation lists, please see the SNMMI online program here. Indication and Important Safety Information About Axumin INDICATION Axumin® (fluciclovine F 18) injection is indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment. IMPORTANT SAFETY INFORMATION Image interpretation errors can occur with Axumin PET imaging. A negative image does not rule out recurrent prostate cancer and a positive image does not confirm its presence. The performance of Axumin seems to be affected by PSA levels. Axumin uptake may occur with other cancers and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological evaluation, is recommended. Hypersensitivity reactions, including anaphylaxis, may occur in patients who receive Axumin. Emergency resuscitation equipment and personnel should be immediately available. Axumin use contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Safe handling practices should be used to minimize radiation exposure to the patient and health care providers. Adverse reactions were reported in ≤ 1% of subjects during clinical studies with Axumin. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia. To report suspected adverse reactions to Axumin, call 1-855-AXUMIN1 (1-855-298-6461) or contact FDA at 1-800-FDA-1088 or . Full Axumin prescribing information is available at . Indication and Important Safety Information About POSLUMA INDICATION POSLUMA® (flotufolastat F 18) injection is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level IMPORTANT SAFETY INFORMATION Image interpretation errors can occur with POSLUMA PET. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of POSLUMA for imaging metastatic pelvic lymph nodes in patients prior to initial definitive therapy seems to be affected by serum PSA levels and risk grouping. The performance of POSLUMA for imaging patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels. Flotufolastat F 18 uptake is not specific for prostate cancer and may occur in other types of cancer, in non-malignant processes, and in normal tissues. Clinical correlation, which may include histopathological evaluation, is recommended. Risk of Image Misinterpretation in Patients with Suspected Prostate Cancer Recurrence: The interpretation of POSLUMA PET may differ depending on imaging readers, particularly in the prostate/prostate bed region. Because of the associated risk of false positive interpretation, consider multidisciplinary consultation and histopathological confirmation when clinical decision-making hinges on flotufolastat F 18 uptake only in the prostate/prostate bed region or only on uptake interpreted as borderline. POSLUMA use contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Advise patients to hydrate before and after administration and to void frequently after administration. Ensure safe handling to minimize radiation exposure to the patient and health care providers. The adverse reactions reported in ≥0.4% of patients in clinical studies were diarrhea, blood pressure increase and injection site pain. Drug Interactions: androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F 18 in prostate cancer. The effect of these therapies on performance of POSLUMA PET has not been established. To report suspected adverse reactions to POSLUMA, call 1-844-POSLUMA (1-844-767-5862) or contact FDA at 1-800-FDA-1088 or . Full POSLUMA prescribing information is available at . About Blue Earth Diagnostics Blue Earth Diagnostics, an indirect subsidiary of Bracco Imaging S.p.A., is a growing international molecular imaging company focused on delivering innovative, well-differentiated diagnostic solutions that inform patient care. Formed in 2014, the Company’s success is driven by its management expertise and supported by a demonstrated track record of rapid development and commercialization of positron emission tomography (PET) radiopharmaceuticals. Blue Earth Diagnostics’ expanding oncology portfolio encompasses a variety of disease states, including prostate cancer and neuro-oncology. Blue Earth Diagnostics is committed to the timely development and commercialization of precision radiopharmaceuticals for potential use in imaging and therapy. For more information, please visit: . About Bracco Imaging Bracco Imaging S.p.A., part of the Bracco Group, is a world-leading diagnostic imaging provider. Headquartered in Milan, Italy, Bracco Imaging develops, manufactures and markets diagnostic imaging agents and solutions. It offers a product and solution portfolio for all key diagnostic imaging modalities: X-ray imaging (including Computed Tomography-CT, Interventional Radiology, and Cardiac Catheterization), Magnetic Resonance Imaging (MRI), Contrast Enhanced Ultrasound (CEUS), and Nuclear Medicine through radioactive tracers and novel PET imaging agents to inform clinical management and guide care for cancer patients in areas of unmet medical need. Our continually evolving portfolio is completed by a range of medical devices, advanced administration systems and dose-management software. In 2019 Bracco Imaging enriched its product portfolio by expanding the range of oncology nuclear imaging solutions in the urology segment and other specialties with the acquisition of Blue Earth Diagnostics. In 2021, Bracco Imaging established Blue Earth Therapeutics as a separate, cutting-edge biotechnology vehicle to develop radiopharmaceutical therapies. Visit: . Axumin and POSLUMA are registered trademarks of Blue Earth Diagnostics Ltd. PP-rh-US-0492 This press release is for U.S. audiences only

Radiation TherapyDiagnostic Reagents

08 Apr 2024

·www.biospace.com

Blue Earth Therapeutics Announces Promising Results from Preclinical Evaluation of Synergistic Drug Combinations with Radiopharmaceutical 177Lu-rhPSMA-10.1 for Treatment of Prostate Cancer

− 177Lutetium-labeled radiohybrid Prostate-Specific Membrane Antigen (177Lu-rhPSMA-10.1) is in development as a highly optimized, next generation therapeutic radiopharmaceutical – − Combination of MEK inhibitor cobimetinib with 177Lu-rhPSMA-10.1 radioligand therapy showed enhanced therapeutic effect versus single agents in preclinical models – − Research presented at AACR Annual Meeting 2024 complements Company’s ongoing Phase 1/2 clinical trial of 177Lu-rhPSMA-10.1 in men with metastatic castrate resistant prostate cancer – MONROE TOWNSHIP, N.J. & OXFORD, England--(BUSINESS WIRE)-- Blue Earth Therapeutics, a Bracco company and emerging leader in the development of innovative next generation therapeutic radiopharmaceuticals, today announced results from a series of preclinical analyses designed to identify synergistic combinations of known anticancer drugs with 177Lu-rhPSMA-10.1 radioligand therapy, and from a preclinical efficacy analysis of the lead novel drug combination for the treatment of prostate cancer. Results from a systematic in vitro screen identified MEK inhibitor cobimetinib as a lead candidate with potential for synergistic combination with 177Lu-rhPSMA-10.1, and the preclinical efficacy analysis showed enhanced therapeutic effect of this drug combination when compared to the untreated control and to the single agents alone. The data were presented in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego, Calif. 177Lu-rhPSMA-10.1, an investigational radiohybrid (rh) Prostate-Specific Membrane Antigen-targeted therapeutic radiopharmaceutical, is the lead candidate in Blue Earth Therapeutics’ oncology development program of next generation therapeutic radiopharmaceuticals. “Radioligand therapy targeting PSMA has been shown to be an effective therapy in men with prostate cancer, and we are pleased to share these promising preclinical results from our study of 177Lu-rhPSMA-10.1 drug combinations with the scientific community at the prestigious AACR Annual Meeting 2024,” said David E. Gauden, D.Phil., Chief Executive Officer of Blue Earth Therapeutics. “Combination approaches are of increasing interest among the medical community, as we know tumors are heterogeneous and some prostate cancer cells do not express PSMA. Importantly, these combinations need to avoid overlapping toxicity. Results from this preclinical study presented at AACR demonstrated a synergistic therapeutic effect between 177Lu-rhPSMA-10.1 and an MEK inhibitor. This may be due to inhibition of the MEK-MAPK pathway during DNA damage response, resulting in radiosensitization of cancer cells to 177Lu-rhPSMA-10.1. Our ongoing Phase 1/2 clinical trial (NCT05413850) is evaluating 177Lu-rhPSMA-10.1 radioligand therapy as a monotherapy in treating men with metastatic castrate resistant prostate cancer, and we may look to evaluate this combination in the clinic in the future.” About the study More than 150 FDA-approved anticancer drugs were screened in a clonogenic survival assay of 22Rv1 cells using the test drug alone, at a range of concentrations <20 µM to determine the IC50. The results were then compared to incubations of the drug plus 15 MBq/mL 177Lu-rhPSMA-10.1 (2-hour incubation) after 10 days. Five lead candidates were then selected for a focused screen where the impact of 177Lu-rhPSMA-10.1 (0–25 MBq/mL) on the drug IC50 was determined. A synergy score was determined using the zero interaction potency (ZIP) reference model and the multi-dimensional synergy of combinations (MuSyc) platform. Therapeutic efficacy of the lead combination, 177Lu-rhPSMA-10.1 (single 30 MBq iv dose) plus cobimetinib (0.25 mg orally per day for 21 days), was then evaluated in 22Rv1 prostate tumor xenograft models and compared to the single agents alone (n = 8 per group, plus untreated controls). Tumor volume was measured 2 times per week for 69 days. Two-way ANOVA and Tukey’s multiple comparisons test (data analyzed until n = 3 remained per group) and Kaplan-Meier Log-rank survival analyses were performed. Results The in vitro screen identified the MEK inhibitor cobimetinib as a lead candidate for synergistic combination with 177Lu-rhPSMA-10.1 across a wide concentration range, with a ZIP synergy score of 13.25% (95% CI ± 2.17) and promising results on MuSyc analysis. The 177Lu-rhPSMA-10.1 plus cobimetinib MEK inhibitor combination significantly suppressed tumor growth in vivo versus untreated controls (from day 13–30; p<0.01) and 177Lu-rhPSMA-10.1 alone (from day 17–30; p<0.001). The median survival in the combination group (49 days) was significantly longer versus the untreated group (23 days; p=0.001) and the group treated with 177Lu-rhPSMA-10.1 alone (36 days; p=0.002). The results were discussed in a poster presentation, “Evaluation of a synergistic drug combination with 177Lu-rhPSMA-10.1 for prostate cancer: Results of an in vitro screen and in vivo proof of concept study,” by Caroline Foxton, Ph.D., Blue Earth Group, Oxford, UK, at the AACR Annual Meeting 2024 on April 7, 2024. The abstract is available in the online program here . About Radiohybrid Prostate-Specific Membrane Antigen (rhPSMA) rhPSMA compounds are referred to as radiohybrid (“rh”), as each molecule possesses three distinct domains. The first consists of a Prostate-Specific Membrane Antigen-targeted receptor ligand which attaches to and is internalized by prostate cancer cells. It is attached to two labelling moieties which may be radiolabeled with diagnostic isotopes such as 18F or 68Ga for PET imaging, or with therapeutic isotopes such as 177Lu or 225Ac for radioligand therapy – enabling the potential for a true theranostic technology. They may play an important role in patient management in the future, and offer the potential for precision medicine for men with prostate cancer. Radiohybrid technology and rhPSMA originated from the Technical University of Munich, Germany. Blue Earth Diagnostics acquired exclusive, worldwide rights to rhPSMA diagnostic imaging technology from Scintomics GmbH in 2018, and therapeutic rights in 2020, and has sublicensed the therapeutic application to its sister company Blue Earth Therapeutics. Blue Earth Therapeutics and Blue Earth Diagnostics work closely on the development of 177Lu-rhPSMA-10.1. Currently, Blue Earth Therapeutics’ rhPSMA compounds have not received regulatory approval. About Blue Earth Therapeutics Blue Earth Therapeutics, one of the Bracco family of companies, is a clinical stage company dedicated to advancing next generation targeted radiotherapeutics to treat patients who have cancer. With proven management expertise across the spectrum of radiopharmaceutical and oncology drug development, as well as biotechnology start-up experience, the Company aims to innovate and improve upon current technologies and rapidly advance new targeted therapies for serious diseases. Blue Earth Therapeutics has an emerging pipeline, initially focused on prostate cancer, and with plans to expand into additional disease areas in oncology. Blue Earth Therapeutics is an indirect subsidiary of Bracco Imaging S.p.A, and based in Oxford, UK. For more information, please visit: . About Bracco Imaging Bracco Imaging S.p.A., part of the Bracco Group, is a world-leading diagnostic imaging provider. Headquartered in Milan, Italy, Bracco Imaging develops, manufactures and markets diagnostic imaging agents and solutions. It offers a product and solution portfolio for all key diagnostic imaging modalities: X-ray imaging (including Computed Tomography-CT, Interventional Radiology, and Cardiac Catheterization), Magnetic Resonance Imaging (MRI), Contrast Enhanced Ultrasound (CEUS), and Nuclear Medicine through radioactive tracers and novel PET imaging agents to inform clinical management and guide care for cancer patients in areas of unmet medical need. Our continually evolving portfolio is completed by a range of medical devices, advanced administration systems and dose-management software. In 2019, Bracco Imaging enriched its product portfolio by expanding the range of oncology nuclear imaging solutions in the urology segment and other specialties with the acquisition of Blue Earth Diagnostics. In 2021, Bracco Imaging established Blue Earth Therapeutics as a separate, cutting-edge biotechnology vehicle to develop radiopharmaceutical therapies. Visit: . This press release is for U.S. audiences only

Clinical Result

100 Deals associated with Flotufolastat F-18

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Prostatic Cancer	US	Blue Earth Diagnostics Ltd.Startup	25 May 2023

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Adenocarcinoma of prostate	Phase 2	US	Blue Earth Diagnostics Ltd.Startup	27 Apr 2023
Non-metastatic prostate cancer	Phase 2	US	Blue Earth Diagnostics Ltd.Startup	27 Apr 2023
Recurrent Prostate Carcinoma	Phase 2	US	Blue Earth Diagnostics Ltd.Startup	27 Apr 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04186819 \| NCT04186845 (SPOTLIGHT, Literature) Manual	Not Applicable	Prostatic Cancer	712	POSLUMA	tzfkzqqsko(eoydjutbib) = vfdkgkvndn zkheztnjvc (lstiamhcvo ) View more	Positive	06 Nov 2023
NCT04186819 (LIGHTHOUSE, ASCO_GU2023) Manual	Phase 3	Prostatic Cancer	335	18F-rhPSMA-7.3	bxmvuyochv(jupxhuhxge) = siyonzarwq kplyplfzly (dfgiiaanfz, 4.2 - 9.8) View more	Positive	21 Feb 2023
NCT04186845 (SPOTLIGHT, ASCO_GU2022) Manual	Phase 3	Prostatic Cancer PSA	389	18 F-rhPSMA-7.3	zdqtgujyoa(tkzfhfrxdo) = hodehhvuid qvwjtfepcv (dinogadjna, 51.6 - 62.0) View more	Positive	16 Feb 2022
NCT04186845 (SPOTLIGHT, ASCO_GU2022) Manual	Phase 3	Prostatic Cancer PSA	389	18 F-rhPSMA-7.3 (patients with a histopathology-only SoT)	zdqtgujyoa(tkzfhfrxdo) = iwndwubdfy qvwjtfepcv (dinogadjna, 69.9 - 89.6) View more	Positive	16 Feb 2022

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