TAT-11: Targeted Radioimmunotherapy and Theranostics

Ottawa, ON, Canada (UroToday.com) Dr. Pandit-Taskar began with a review of the basics and rationale for targeted alpha therapy. She emphasized the high LET of alpha particles that deliver a high dose to the tumor but, because of the short-range cause lower toxicity to healthy surrounding tissue. She touched on some of the challenges such as the stability of the chelation and the release of radioisotope from the recoil of the first alpha in the decay chain, making it imperative to monitor the dose to the blood and organs distant from the tumor being treated. Damage to the bone marrow can often be the dose-limiting factor.

Dr. Pandit-Taskar emphasized the need for high-quality imaging. The "theranostics" in the title is a relatively new term to capture the complementary aspects of therapy and imaging for diagnostics. Imaging is crucial for determining the heterogeneity of the dose distribution and tumor penetration.

Dr. Pandit-Taskar reviewed some of the factors in optimizing therapy including choice of an isotope, antibody (including the possible use of minibodies), and techniques such as pre-loading to improve biodistribution. The proper selection of imaging and therapeutic agent pairs (e.g., Zr89/Ac225) is the key to successful theranostics. She reviewed several examples:

Ac225-J591 for metastatic prostate cancer, now moving to Phase I after mouse model studies
Y90-cG250 for renal cell carcinoma, now entering Phase I to study dose escalation
Phase II Lu177-girentuximab for advanced renal cell carcinoma

She mentioned localized, compartmental therapies where the radioisotope is injected directly into the tumor site. Brain gliomas are a good example. When treated with At211 and imaged with I1124-omburtamab showed very efficient delivery to the tumor with a ratio of 300:1 in radiation to the tumor versus neighboring brain tissue.

For future directions, Dr. Pandit-Taskar mentioned multi-step targeting (also referred to as "click chemistry" where the antibody is pre-loaded. After rapid clearing, the labeled radioisotope is introduced, and it then links in vivo with the antibody already attached to the tumor. She closed with several charts that documented many clinical trials with various isotopes/antibody pairs targeting a wide range of targeted tumors. She summarized with a call for larger, well-designed multicenter studies.

Presented by: Neeta Pandit-Taskar, MD, Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center & Clinical Director, Center for Radoimmunotargeting Imaging and Theranostics, Ludwig Center for Cancer Immunotherapy

Written by: William Carithers, Lawrence Berkeley National Laboratory at the 11th International Symposium on Targeted Alpha Therapy (TAT-10) April 1 - April 4, 2019 - Ottawa, ON, Canada

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