![]() ![]() N.K.C is the inventor and owner of issued patents licensed by MSK to Y-mAbs Therapeutics, Biotec Pharmacon, and Abpro Labs. N.K.C is a scientific advisory board member of Abpro Labs and Eureka Therapeutics. S.M.L reports receiving commercial research grants from Genentech, Inc., WILEX AG, Telix Pharmaceuticals Limited, and Regeneron Pharmaceuticals, Inc. holding ownership interest/equity in Elucida Oncology, Inc. and Y-mAbs Therapeutics, and holding stock in ImaginAb, Inc. S.M.L is the inventor and owner of issued patents both currently unlicensed and licensed by MSK to Samus Therapeutics, Inc., Elucida Oncology, Inc., and Y-mAbs Therapeutics, Inc. ![]() S.M.L serves or has served as a consultant to Cynvec LLC, Eli Lilly & Co., Prescient Therapeutics Limited, Advanced Innovative Partners, LLC, Gerson Lehrman Group, Progenics Pharmaceuticals, Inc., and Janssen Pharmaceuticals, Inc. G.Y and O.O are listed as inventors and receive royalties from patents that were filed by MSK. O.O is an unpaid member of the scientific advisory board of Angiogenex and owns shares in Angiogenex. B.H.S and N.K.C are inventors on US Patent No. D.A.S is a consultant to, on the board of, and/or has equity in: PGNX, SLS, KLUS, IOVA, PFE, ATNM, Oncopep and Eureka Therapeutics. MSK has filed for patent protection on behalf of D.A.S for technology discussed in this paper. All other authors have no competing interests. This is the initial report of an α-based pre-targeted radioimmunotherapy (PRIT) using 225Ac and its theranostic pair, 111In. We call our novel tumor-targeting DOTA-hapten PRIT system “proteus-DOTA” or “Pr.” Herein we report the first results of radiochemistry development, radiopharmacology, and stoichiometry of tumor antigen binding, including the role of specific activity, anti-tumor efficacy, and normal tissue toxicity with the Pr-PRIT approach (as α-DOTA-PRIT). #Proteus for escalations seriesĪ series of α-DOTA-PRIT therapy studies were performed in three solid human cancer xenograft models of colorectal cancer (GPA33), breast cancer (HER2), and neuroblastoma (GD2), including evaluation of chronic toxicity at ~20 weeks of select survivors. Methods: Preliminary biodistribution experiments in SW1222 tumor-bearing mice revealed that 225Ac could not be efficiently pretargeted with current DOTA-Bn hapten utilized for 177Lu or 90Y, leading to poor tumor uptake in vivo. ![]() Therefore, we synthesized Pr consisting of an empty DOTA-chelate for 225Ac, tethered via a short polyethylene glycol linker to a lutetium-complexed DOTA for picomolar anti-DOTA chelate single-chain variable fragment (scFv) binding. ![]() Pr was radiolabeled with 225Ac and its imaging surrogate, 111In. ![]()
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