Author: Salah, Samer ; Al-Hajaj, Nabeela ; Al-Ibraheem, Akram ; Abu-Hijlih, Ramiz ; Abdlkadir, Ahmed Saad ; Abufara, Alaa' ; Istatieh, Feras ; Sharaf, Baha

01 Jul 2024·Seminars in Nuclear Medicine

Navigating The Prostate Cancer Frontier: A Bibliometric and Altmetric Analysis of [225Ac]Ac-PSMA Therapy

Review

Author: Abdlkadir, Ahmed Saad ; Al-Ibraheem, Akram ; Ghesani, Munir ; Alyasjeen, Salem Fandi ; Al-Rashdan, Rakan ; Sweedat, Deya' Aldeen ; Buscombe, John R ; Kairemo, Kalevi ; Al-Abdallat, Haneen

The main aim of this study was to evaluate the current state of bibliometric and altmetric research output of [²²⁵Ac]Ac-Prostate specific membrane antigen (PSMA) and its implications for prostate cancer (PC). Both PubMed and Scopus digital libraries were systematically explored to retrieve relevant data on the topic of interest. The study of various bibliometric and altmetric indices was facilitated through the use of Microsoft Excel, Stata (Version 17.0), and VOSviewer (Version 1.6) Softwares. The parameters included in this study comprised the examination of published articles, annual trends, countries, institutions, authors, journals, and co-occurring keywords. From 2014 to 2024, our study examined a total of 100 publications within the given domain. The studies that received the highest citations primarily centered on the crucial topic of metastatic castration-resistant prostate cancer, with a particular emphasis on evaluating the safety and effectiveness of [²²⁵Ac]Ac-PSMA therapy. Moreover, much scholarly inquiry has been devoted to examining the [²²⁵Ac]Ac-PSMA adverse effects. Three high prolific countries (namely, Germany, United States, and South Africa) dominated the research render in terms of publications and citations. Finally, A strong correlation was observed between altmetric score and citation number (P < 0.001). The observed surge in scholarly research output and altmetric indicators associated with [²²⁵Ac]Ac-PSMA signifies a shift in emphasis towards embracing alpha targeted therapy in PC.

01 Mar 2024·Journal of Nuclear Medicine

Effectiveness of²²⁵Ac-Labeled Anti-EGFR Radioimmunoconjugate in EGFR-Positive Kirsten Rat Sarcoma Viral Oncogene and BRAF Mutant Colorectal Cancer Models

Article

Author: Tikum, Anjong Florence ; Njotu, Fabrice Ngoh ; Babeker, Hanan ; Ketchemen, Jessica P ; Fonge, Humphrey ; Doroudi, Alireza ; Nambisan, Anand K

Eighty percent of colorectal cancers (CRCs) overexpress epidermal growth factor receptor (EGFR). Kirsten rat sarcoma viral oncogene (KRAS) mutations are present in 40% of CRCs and drive de novo resistance to anti-EGFR drugs. BRAF oncogene is mutated in 7%-10% of CRCs, with even worse prognosis. We have evaluated the effectiveness of [²²⁵Ac]Ac-macropa-nimotuzumab in KRAS mutant and in KRAS wild-type and BRAF^V600E mutant EGFR-positive CRC cells in vitro and in vivo. Anti-CD20 [²²⁵Ac]Ac-macropa-rituximab was developed and used as a nonspecific radioimmunoconjugate. Methods: Anti-EGFR antibody nimotuzumab was radiolabeled with ²²⁵Ac via an 18-membered macrocyclic chelator p-SCN-macropa. The immunoconjugate was characterized using flow cytometry, radioligand binding assay, and high-performance liquid chromatography, and internalization was studied using live-cell imaging. In vitro cytotoxicity was evaluated in 2-dimensional monolayer EGFR-positive KRAS mutant DLD-1, SW620, and SNU-C2B; in KRAS wild-type and BRAF^V600E mutant HT-29 CRC cell lines; and in 3-dimensional spheroids. Dosimetry was studied in healthy mice. The in vivo efficacy of [²²⁵Ac]Ac-macropa-nimotuzumab was evaluated in mice bearing DLD-1, SW620, and HT-29 xenografts after treatment with 3 doses of 13 kBq/dose administered 10 d apart. Results: In all cell lines, in vitro studies showed enhanced cytotoxicity of [²²⁵Ac]Ac-macropa-nimotuzumab compared with nimotuzumab and controls. The inhibitory concentration of 50% in the DLD-1 cell line was 1.8 nM for [²²⁵Ac]Ac-macropa-nimotuzumab versus 84.1 nM for nimotuzumab. Similarly, the inhibitory concentration of 50% was up to 79-fold lower for [²²⁵Ac]Ac-macropa-nimotuzumab than for nimotuzumab in KRAS mutant SNU-C2B and SW620 and in KRAS wild-type and BRAF^V600E mutant HT-29 CRC cell lines. A similar trend was observed for 3-dimensional spheroids. Internalization peaked 24-48 h after incubation and depended on EGFR expression. In the [²²⁵Ac]Ac-macropa-nimotuzumab group, 3 of 7 mice bearing DLD-1 tumors had complete remission. Median survival was 40 and 34 d for mice treated with phosphate-buffered saline and [²²⁵Ac]Ac-macropa-rituximab (control), respectively, whereas it was not reached for the [²²⁵Ac]Ac-macropa-nimotuzumab group (>90 d). Similarly, median survival of mice bearing HT-29 xenografts was 16 and 12.5 d for those treated with [²²⁵Ac]Ac-macropa-rituximab and phosphate-buffered saline, respectively, and was not reached for those treated with [²²⁵Ac]Ac-macropa-nimotuzumab (>90 d). One of 7 mice bearing HT-29 xenografts and treated using [²²⁵Ac]Ac-macropa-nimotuzumab had complete remission. Compared with untreated mice, [²²⁵Ac]Ac-macropa-nimotuzumab more than doubled (16 vs. 41 d) the median survival of mice bearing SW620 xenografts. Conclusion: [²²⁵Ac]Ac-macropa-nimotuzumab is effective against KRAS mutant and BRAF^V600E mutant CRC models.

100 Deals associated with [225Ac]Ac-SibuDAB

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Indication	Highest Phase	Country/Location	Organization	Date
Prostatic Cancer	Preclinical	CH	Paul Scherrer Institut PSI	17 Nov 2022

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