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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, c1995-

Melanoma* ; Receptor, Melanocortin, Type 1*; Animals ; Chelating Agents ; Chlorides ; Humans ; Lead ; Ligands ; Mice ; Thallium Radioisotopes ; Tissue Distribution

[ 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.

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P30 ES005605 United States ES NIEHS NIH HHS; P30 CA086862 United States CA NCI NIH HHS; R44 CA250872 United States CA NCI NIH HHS; R01 CA243014 United States CA NCI NIH HHS; R44 CA254613 United States CA NCI NIH HHS; R44CA254613 National Institute of Health; NIH R01CA243014 National Institute of Health; R44CA250872 National Institute of Health

Keywords: 203Pb; 208Tl; 212Pb; MC1R; absorbed dose; dosimetry; melanoma

0 (Chelating Agents)
0 (Chlorides)
0 (Ligands)
0 (Receptor, Melanocortin, Type 1)
0 (Thallium Radioisotopes)
2P299V784P (Lead)

Date Created: 20220923 Date Completed: 20220926 Latest Revision: 20230127

20240513

PMC9504749

10.3390/molecules27185831

36144563