Hexin (Suzhou) Pharmaceutical Technology Co Ltd.

Tumor-associated neovasculature and energy metabolism reprogramming serve as critical indicators of tumor proliferation, progression, invasion, and metastasis. This study conducted a head-to-head clinical investigation and comparison of [¹⁸F]FDG and [⁶⁸Ga]Ga-HX01 PET by reflecting neovasculature and glucose metabolism in sarcoma patients, respectively.

We reviewed the imaging data of sarcoma patients who underwent [⁶⁸Ga]Ga-HX01 PET/MR and [¹⁸F]FDG PET/CT from June 29, 2022, to December 21, 2023. The two imaging modalities were performed on two separate days within one week of each other. A cohort of 21 patients with an average age of 45.81 ± 19.99 years were enrolled. The location, number and PET characteristics of all lesions were collected. The relationships between the two tracers were evaluated.

Among the 21 patients, 4 underwent imaging for initial disease staging, while the remaining 17 were imaged to detect recurrences. Patient-based analysis revealed that [⁶⁸Ga]Ga-HX01 PET/MR diagnostic performance was equivalent to [¹⁸F]FDG PET/CT in lesion detection (P = 1.0). The SUVmax value of [⁶⁸Ga]Ga-HX01 (4.64 ± 1.90) was significantly lower than that of [¹⁸F]FDG (9.43 ± 6.17, P = 0.002) across all patients. In terms of lesion-based analysis, [⁶⁸Ga]Ga-HX01 identified two additional lesions compared to [¹⁸F]FDG, though this difference was not statistically significant (94 vs. 92, P = 0.678). The SUVmax value for all lesions with [⁶⁸Ga]Ga-HX01 (3.47 ± 1.68) was also lower than that with [¹⁸F]FDG (5.82 ± 4.81, P = 0.003). Notably, [⁶⁸Ga]Ga-HX01 was preferred in patients receiving hematopoietic cytokines.

[⁶⁸Ga]Ga-HX01 PET offers comparable diagnostic efficacy to [¹⁸F]FDG PET/CT in sarcoma, with potential advantages in specific clinical scenarios. Larger cohorts are needed to validate these findings.

NCT05490849 and NCT06416774.

Angiogenesis is essential in the development and progression of tumors. This study aimed to investigate the clinical application of 68Ga-labeled heterodimeric peptide (68Ga-HX01) targeting integrin αvβ3 and CD13 in tumor neovascularization.

Six healthy volunteers were recruited to study the biodistribution, pharmacokinetics, and radiation of 68Ga-HX01. Twelve patients with various malignancies were enrolled to seek the preliminary clinical value of 68Ga-HX01. In healthy volunteers, SUVs of each major organ on 68Ga-HX01 PET were measured. The clinical data, lesion numbers, and uptake were recorded in patients. The integrin αvβ3 and CD13 expression of the resected tumors was checked via immunohistochemistry staining.

With a mean injected dose of 167.98 ± 26.32 MBq, 68Ga-HX01 was well tolerated and safe without side effects in 6 healthy volunteers. The radiation absorbed effective dose of 68Ga-HX01 was 1.94 × 10−2 mSv/MBq, and the urinary bladder wall held the highest absorbed effective dose (0.15 ± 5.87 × 10−2 mSv/MBq). In 12 patients with various malignancies, 68Ga-HX01 PET could clearly visualize the lesions from the surrounding tissues. The SUVmax values in tumors were significantly higher than those in the surrounding tissues (P < 0.05). A positive correlation trend between tumor SUVmax and semiquantitative integrin αvβ3 and CD13 expression was determined (P < 0.05).

For clinical use, 68Ga-HX01 is safe with low radiation absorbed effective dose. It also indicates the efficiency of dual integrin αvβ3 and CD13-targeting PET radiotracer in tumor diagnosis, which may assist in patient prognosis and selecting eligible patients for antiangiogenic therapy.

Noninvasive angiogenesis visualization is essential for evaluating tumor proliferation, progression, invasion, and metastasis. This study aimed to translate the heterodimeric PET tracer [⁶⁸Ga]Ga-HX01, which targets integrin αvβ3 and CD13 in neovascularization, into phase I clinical study.

This study enrolled 12 healthy volunteers (phase Ia) and 10 patients with malignant tumors (phase Ib). The subjects in phase Ia were divided into low-dose (0.05 mCi/kg) and high-dose (0.1 mCi/kg) groups. For phase Ia subjects, PET/CT images, blood and urine samples were collected to analyze the biodistribution, pharmacokinetics, radiation dosimetry, and safety of [⁶⁸Ga]Ga-HX01. For phase Ib patients, PET/MR scans were performed at 30 ± 5 and 60 ± 5 min after injection. The safety and preliminary diagnostic value of [⁶⁸Ga]Ga-HX01 were assessed.

In phase Ia study, [⁶⁸Ga]Ga-HX01 was distributed and metabolized similarly in two dosage groups as the highest accumulations in kidneys and urine. It possessed quick renal excretion and blood clearance with an elimination half-life (T_1/2) of 28.92 ± 3.97 min. The total effective dose was 2.14 × 10^- 2 mSv/MBq. In phase Ib study, [⁶⁸Ga]Ga-HX01 clearly detected the lesions per patient, and found a total of 59 lesions with varying uptake levels. For safety evaluation, no serious adverse events were observed during the examination.

[⁶⁸Ga]Ga-HX01 has proved to be a translational radiopharmaceutical with reliable security, favorable pharmacokinetics, and the ability to visualize tumors. The preliminary results in malignancy patients warrant further investigation of [⁶⁸Ga]Ga-HX01 in monitoring antiangiogenic therapy of patients with malignancies.

ClinicalTrials.gov, NCT06416774. Registered 11 May, 2024.