English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

[ 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.

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