Targeted beta therapy of human prostate cancer in vivo with Lu-177 labelled Miltuximab textregistered antibody against glypican-1 ( GPC-1 )

Mei-Chun Yeh, Brian W. C. Tse, Nicholas L. Fletcher, Zachary H. Huston, Chelsea Stewart, Kamil Sokolowski, Varinder Jeet, Kristofer J. Thurecht, Douglas H. Campbell, Bradley J. Walsh, Colleen C. Nelson, Pamela J. Russell

Research output: Contribution to journalMeeting abstract

Abstract

Aim: To assess targeted beta therapy of human prostate cancer in vivo with Lu‐177 labelled MIL‐38 monoclonal antibody which binds GPC‐1. Minomic International Ltd have previously shown that MIL‐38 (previously known as BLCA‐38) binds to surface antigens present on DU145 cells via flow cytometry, western blotting and immuno‐precipitationa. Another study showed a single injection of 213Bi‐labeled multiple targeted α radio‐immunoconjugates (MTAT) which included BLCA‐38, prevented PC3 cell growth and metastases in various mouse modelsb. These data suggest that MIL‐38 could be a potential marker for the detection and therapy of prostate cancer.

Methods: Male Balb/c/nude mice (6–8 weeks old) were inoculated subcutaneously with DU145‐RFP‐Luc cells (5 × 106) in PBS:matrigel (1:1) in the right flank. Once the tumour reached palpable size, the mice were then treated with either chMIL‐38‐DOTA or 177Lu‐chMIL‐38‐DOTA intravenously and sacrificed either on day 3, 5 and 7 or once the control tumour reached 1000 mm3. Tissues were harvested and radioactivity in the organs were measured via gamma counter.

Results: We demonstrated that 177Lu‐chMIL‐38‐DOTA significantly inhibited tumour growth by 50% after a single dose. The inhibition on tumour growth is dose dependent and was observed as early as 6 days post lutetium treatment. Results from biodistribution study showed that the uptake of the antibody by the tumour was the highest across all time points except for spleen at day 7. Independent pathology assessment of tissue toxicity showed minimum cytotoxicity in most tissues.

Conclusion: These data demonstrated the potential usage of targeted beta therapy with 177Lu‐chMIL‐38‐DOTA in prostate cancer.
Original languageEnglish
Article number78
Pages (from-to)34-35
Number of pages2
JournalBJU International
Volume122
Issue numberS2
Publication statusPublished - Aug 2018
Event19th Asia-Pacific Prostate Cancer Conference - Brisbane, Australia
Duration: 22 Aug 201825 Aug 2018

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