PI-124 - AN INTEGRATED ANALYSIS OF FOUR TARGETED THORIUM CONJUGATES TO ASSESS THE TH-227 AND RA-223 DISTRIBUTION AND TISSUE-RELATED RADIATION.

M. Block¹, A. Cleton², C. Zieschang², S. Johanssen², T. Poethko³, H. Hennekes², C. Niederalt¹; ¹Bayer AG, Leverkusen, Germany, ²Bayer AG, Berlin, Germany, ³Bayer AG, Wuppertal, Germany.

Background: The aim of this analysis is to assess on a tissue level the distribution of thorium-227 (Th-227) and radium-223 (Ra-223) activities in monkeys originating from four different Targeted Thorium conjugates (TTCs) and to clarify the extent of elimination by physical decay and redistribution from tissues for both radionuclides. The clinical translatability of the findings is evaluated by use of human data from a Phase I study in cancer patients.

Methods: Data from monkey studies with four different TTCs were used to analyze the impact of redistribution or net flow from tissues of Th-227 and Ra-223 on radiation by comparison to the model-based predicted radioactivity without any redistribution (reference activity) i.e., assuming physical decay as the only elimination pathway from tissues. For comparison to the clinical situation whole-body activities of cancer patients measured by High-Purity Germanium detectors (HPGe) from a First in Human (FiH) study of CD22-TTC were assessed in a similar way.

Results: The integrated analysis demonstrated for all TTCs that for Th-227 physical decay without a strong redistribution from organs is the main elimination path, whereas the first daughter nuclide Ra-223 shows in addition to physical decay a fast and strong redistribution from most of the tissues except for bone and (large) intestine. The intestine is an elimination organ for Ra-223, while the lack of redistribution from bone is consistent with data obtained with Ra-223 chloride. The analysis showed that the findings are independent of compound, target, dose, and administered activity. Results based on the monkey studies are also consistent with clinical data.

Conclusion: In conclusion, the detailed assessment revealed the tissue related distribution and redistribution behavior of Th-227 and its daughter nuclide Ra-223. The overarching consistency of the findings across different TTCs and the agreement with clinical observations can be used to drive decisions along the clinical development based on expected distribution and related radiation of both radionuclides.