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

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• 作者：Sangeeta Ray Banerjee ; Mrudula Pullambhatla ; Catherine A. Foss ; Alexander Falk ; Youngjoo Byun ; Sridhar Nimmagadda ; Ronnie C. Mease ; Martin G. Pomper
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：August 8, 2013
• 年：2013
• 卷：56
• 期：15
• 页码：6108-6121
• 全文大小：536K
• 年卷期：v.56,no.15(August 8, 2013)
• ISSN：1520-4804

文摘

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鈥?b>L10), traditional N_xS_y-based chelating agents with varying charge and polarity for the ^99mTc-oxo core (L11鈥?b>L18), and a ^99mTc-organohydrazine-labeled radioligand (L19). ^99mTc(I)-Tricarbonyl-labeled [^99mTc]L8 produced the highest PSMA+ PC3 PIP to PSMA鈥?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.