Effect of Chelators on the Pharmacokinetics of 99mTc-Labeled Imaging Agents for the Prostate-Specific Membrane Antigen (PSMA)

摘要

Technetium-99m, the most commonly used radionuclide in nuclear medicine, can be attached to biologically important molecules through a variety of chelating agents, the choice of which depends upon the imaging application. The prostate-specific membrane antigen (PSMA) is increasingly recognized as an important target for imaging and therapy of prostate cancer (PCa). Three different ^99mTc-labeling methods were employed to investigate the effect of the chelator on the biodistribution and PCa tumor uptake profiles of 12 new urea based PSMA-targeted radiotracers. This series includes hydrophilic ligands for radiolabeling with the [^99mTc(CO)3]⁺ core (>L8->10), traditional NxSy-based chelating agents with varying charge and polarity for the ^99mTc-oxo core (>L11->18), and a ^99mTc-organohydrazine-labeled radioligand (>L19). ^99mTc(I)-Tricarbonyl-labeled [^99mTc]>L8 produced the highest PSMA+ PC3 PIP to PSMA− PC3 flu tumor ratios, and demonstrated the lowest retention in normal tissues including kidney after 2 h. These results suggest that choice of chelator is an important pharmacokinetic consideration in the development of ^99mTc-labeled radiopharmaceuticals targeting PSMA.