A Series of PSMA-Targeted Near-Infrared Fluorescent Imaging Agents

Ying Chen; Il Minn; Steven P. Rowe; Alla Lisok; Samit Chatterjee; Mary Brummet; Sangeeta Ray Banerjee; Ronnie C. Mease; Martin G. Pomper

doi:10.3390/biom12030405

Biomolecules (Mar 2022)

A Series of PSMA-Targeted Near-Infrared Fluorescent Imaging Agents

Ying Chen,
Il Minn,
Steven P. Rowe,
Alla Lisok,
Samit Chatterjee,
Mary Brummet,
Sangeeta Ray Banerjee,
Ronnie C. Mease,
Martin G. Pomper

Affiliations

Ying Chen: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Il Minn: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Steven P. Rowe: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Alla Lisok: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Samit Chatterjee: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Mary Brummet: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Sangeeta Ray Banerjee: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Ronnie C. Mease: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Martin G. Pomper: The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

DOI: https://doi.org/10.3390/biom12030405
Journal volume & issue: Vol. 12, no. 3
p. 405

Abstract

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We have synthesized a series of 10 new, PSMA-targeted, near-infrared imaging agents intended for use in vivo for fluorescence-guided surgery (FGS). Compounds were synthesized from the commercially available amine-reactive active NHS ester of DyLight800. We altered the linker between the PSMA-targeting urea moiety and the fluorophore with a view to improve the pharmacokinetics. Chemical yields for the conjugates ranged from 51% to 86%. The Ki values ranged from 0.10 to 2.19 nM. Inclusion of an N-bromobenzyl substituent at the ε-amino group of lysine enhanced PSMA+ PIP tumor uptake, as did hydrophilic substituents within the linker. The presence of a polyethylene glycol chain within the linker markedly decreased renal uptake. In particular, DyLight800-10 demonstrated high specific uptake relative to background signal within kidney, confirmed by immunohistochemistry. These compounds may be useful for FGS in prostate, renal or other PSMA-expressing cancers.

Published in Biomolecules

ISSN: 2218-273X (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: https://www.mdpi.com/journal/biomolecules

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