Meeting ReportIn vitro and In vivo Oncology

Targeted alpha therapy using astatine (211At)-labeled PSMA5: a preclinical evaluation as a new novel compound.

Tadashi Watabe, Kazuo Kaneda, Yoshifumi Shirakami, Yuichiro Kadonaga, Kazuhiro Ooe, Yang Wang, Hiromitsu Haba, Atsushi Toyoshima and Koichi Fukase
Journal of Nuclear Medicine August 2022, 63 (supplement 2) 4022;

Abstract

4022

Introduction: Alpha therapy targeting prostate specific membrane antigen (PSMA) is a promising therapy for metastatic castration resistant prostate cancer, especially for the refractory cases to [177Lu]PSMA therapy. Astatine is an alpha emitter (half-life=7.2 hrs) which can be produced by the accelerator, and it can be labelled to small molecules and peptides. In this study, we evaluated the treatment effect of 211At labelled PSMA compound ([211At]PSMA5) in mouse xenograft models of prostate cancer.

Methods: Human prostate cancer cells (LNCaP, 0.6*10^7cells) were subcutaneously transplanted into SCID Mouse (5 weeks old, male) and used about 1 month later. For the evaluation of biodistribution, [211At]PSMA1 or [211At]PSMA5 (0.1 MBq) were administered to LNCaP xenograft mice and dissected 3hrs and 24hrs post injection (each n=3). Treatment effect was evaluated by administering [211At]PSMA5 (0.4MBq) (n=6) or saline (n=5) to LNCaP xenograft mice. Tumor size and body weight were monitored for 21 days. Histopathological evaluation was performed for the risk organs (kidney, salivary gland, and thyroid gland) at 21 days after administration.

Results: [211At]PSMA5 showed better tumor retention compared to [211At]PSMA1 (19.1 ± 11.1 and 12.4 ± 4.8 %ID/g at 3hr, 40.7 ± 2.6 and 8.7 ± 3.5 %ID/g at 24hr, respectively), whereas kidney excretion was superior in [211At]PSMA1 compared to [211At]PSMA5. Regarding the treatment effect, excellent tumor growth suppression was observed in LNCaP xenograft after administration of [211At]PSMA5. Tumor shrinkage was observed without regrowth until 21 days after administration. No significant changes were observed in body weight, histopathological evaluation of the kidney, salivary gland, and thyroid gland between [211At]PSMA5 group and control group.

Conclusions: [211At]PSMA5 exhibited an excellent tumor growth suppression in xenograft models of prostate cancer without major toxicity. [211At]PSMA can be applicable as a new targeted alpha therapy in prostate cancer in addition to [225Ac]PSMA-617.

Figure
Figure
Figure
Figure
Back to top

In this issue

Journal of Nuclear Medicine
Vol. 63, Issue supplement 2
August 1, 2022
Article Alerts
Email Article
Citation Tools
Bookmark this article

Jump to section