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

Kelly D Orcutt; Kelly E Henry; Christine Habjan; Keryn Palmer; Jack Heimann; Julie M Cupido; Vijay Gottumukkala; Derek D Cissell; Morgan C Lyon; Amira I Hussein; Dijie Liu; Mengshi Li; Frances L Johnson; Michael K Schultz

doi:10.3390/molecules27185831

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

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

Kelly D Orcutt, Kelly E Henry, Christine Habjan, Keryn Palmer, Jack Heimann, Julie M Cupido, Vijay Gottumukkala, Derek D Cissell, Morgan C Lyon, Amira I Hussein, …

Molecules (Basel, Switzerland), Vol.27(18), p.5831

01/01/2022

DOI: 10.3390/molecules27185831

PMCID: PMC9504749

PMID: 36144563

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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 mGyRBE = 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.

Dosimetry

Pharmacology

a-Melanocyte-stimulating hormone

Alpha decay

Alpha particles

Alpha rays

Biodistribution

Bladder

Chemical compounds

Daughters

Dosimeters

Emission

Emissions

Females

Human tissues

Kidneys

Localization

Males

Melanocortin

Melanoma

Radiation

Retention

Tissues

Tomography

Details

Title: Subtitle: Dosimetry of [212Pb]VMT01, a MC1R-Targeted Alpha Therapeutic Compound, and Effect of Free 208Tl on Tissue Absorbed Doses
Creators: Kelly D Orcutt - Viewpoint Molecular Targeting (United States)
Kelly E Henry
Christine Habjan
Keryn Palmer
Jack Heimann
Julie M Cupido
Vijay Gottumukkala
Derek D Cissell
Morgan C Lyon
Amira I Hussein
Dijie Liu
Mengshi Li
Frances L Johnson
Michael K Schultz
Resource Type: Journal article
Publication Details: Molecules (Basel, Switzerland), Vol.27(18), p.5831
DOI: 10.3390/molecules27185831
PMID: 36144563
PMCID: PMC9504749
NLM abbreviation: Molecules
eISSN: 1420-3049
Publisher: MDPI AG
Grant note: name: National Institute of Health, award: NIH R01CA243014, R44CA250872, R44CA254613
Language: English
Date published: 01/01/2022
Academic Unit: Radiology; Stead Family Department of Pediatrics; Radiation Oncology; Internal Medicine
Record Identifier: 9984296965902771

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