Promising Discovery Could Improve Yield of Radiopharmaceuticals

A discovery from Monopar Therapeutics Inc. and NorthStar Medical Radioisotopes, LLC, could potentially improve efficacy and safety and enhance manufacturing efficiency of Actinium-based radiopharmaceuticals. The companies filed a provisional patent, titled “Bio-Targeted Radiopharmaceutical Compositions Containing Ac-225 and Methods of Preparation,” with the U.S. Patent and Trademark Office (USPTO).

Radiopharmaceutical therapy is a promising approach to treat cancer and other diseases using radioactive metals bound with proteins/antibodies to target and kill cells. Actinium-225 (Ac-225) is emerging as a radioactive isotope of choice for radiopharmaceuticals due to favorable properties such as its long half-life, high potency, and induction of localized cell death.

 “Actinium is quickly becoming a premier radioisotope in cancer-targeting therapies, but its potential is limited due to its price and scarcity,” said James Harvey, PhD, Chief Scientific Officer of NorthStar. “Enabling radiopharmaceutical manufacturers and drug developers to maximize the binding efficiency of Ac-225, and thereby reduce the quantity of Ac-225 required for purchase and use, would permit this promising class of drugs to reach its full potential.”

 This provisional patent relates to the unexpected observation by Monopar and NorthStar that using the metal binding agent 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA) to attach Ac-225 to antibodies resulted in nearly 100% binding of Ac-225 to the PCTA-antibody conjugates. If validated through further evaluation, it could potentially improve efficacy and safety and enhance manufacturing efficiency of Actinium-based radiopharmaceuticals.

 Based on Monopar and NorthStar’s work to date, PCTA-antibody conjugates appear to bind Ac-225 and its daughter ions such as Bi-213 with high affinity. This could be important in the situation of transportation delays resulting in Ac-225 decaying during transport. Furthermore, when compared to DOTA (the standard binding agent for attaching Ac-225 to an antibody), PCTA-antibody conjugates displayed a significantly higher affinity to Ac-225. This high affinity binding may decrease the amount of Ac-225 and its daughter ions that detach from the antibody, which could potentially increase efficacy and reduce off-target toxicity and enable higher dosing. Monopar and NorthStar plan to explore both internal development and out-licensing opportunities of this promising approach in Actinium-based radiopharmaceuticals.

 “Binding Actinium to antibodies using PCTA instead of DOTA has displayed unexpected and unique properties including substantially tighter binding of Ac-225 and a much higher incorporation into the PCTA-antibody conjugate,” said Andrew Mazar, PhD, Chief Scientific Officer of Monopar. “This technology could have broad applicability to the manufacturing of numerous radio-immuno-conjugates and may also extend to other proteins.”