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

Abstract

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