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

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

Automated summary

The goal of this study is to estimate the human dosimetry for [Pb-212]VMT01 and the impact of free Tl-208 in the injectate on human tissue absorbed doses. The results indicate that the dose-limiting tissues for [Pb-212]VMT01 are the red marrow and the kidneys, while absorbed doses from free Tl-208 in the injectate have a minimal increase.