Dosimetry of [(212)Pb]VMT01, a MC1R-Targeted Alpha Therapeutic Compound, and Effect of Free (208)Tl on Tissue Absorbed Doses

[(212)Pb]VMT01 is a melanocortin 1 receptor (MC1R) targeted theranostic ligand in clinical development for alpha particle therapy for melanoma. (212)Pb has an elementally matched gamma-emitting isotope (203)Pb; thus, [(203)Pb]VMT01 can be used as an imaging surrogate for [(212)Pb]VMT01. [(212)Pb]VMT01 human serum stability studies have demonstrated retention of the (212)Bi daughter within the chelator following beta emission of parent (212)Pb. However, the subsequent alpha emission from the decay of (212)Bi into (208)Tl results in the generation of free (208)Tl. Due to the 10.64-hour half-life of (212)Pb, accumulation of free (208)Tl in the injectate will occur. The goal of this work is to estimate the human dosimetry for [(212)Pb]VMT01 and the impact of free (208)Tl in the injectate on human tissue absorbed doses. Human [(212)Pb]VMT01 tissue absorbed doses were estimated from murine [(203)Pb]VMT01 biodistribution data, and human biodistribution values for (201)Tl chloride (a cardiac imaging agent) from published data were used to estimate the dosimetry of free (208)Tl. Results indicate that the dose-limiting tissues for [(212)Pb]VMT01 are the red marrow and the kidneys, with estimated absorbed doses of 1.06 and 8.27 mGy(RBE = 5)/MBq. The estimated percent increase in absorbed doses from free (208)Tl in the injectate is 0.03% and 0.09% to the red marrow and the kidneys, respectively. Absorbed doses from free (208)Tl result in a percent increase of no more than 1.2% over [(212)Pb]VMT01 in any organ or tissue. This latter finding indicates that free (208)Tl in the [(212)Pb]VMT01 injectate will not substantially impact estimated tissue absorbed doses in humans.