Molar Activity of Ga-68 Labeled PSMA Inhibitor Conjugates Determines PET Imaging Results

Molecular Pharmaceutics
Alexander WurzerJohannes Notni

Abstract

Radiopharmaceuticals targeting the enzyme prostate-specific membrane antigen (PSMA; synonyms: glutamate carboxypeptidase II, NAALADase; EC 3.4.17.21) have recently emerged as powerful agents for diagnosis and therapy (theranostics) of prostate carcinoma (PCa). The radiation doses for therapeutic application of such compounds are limited by substantial uptakes in kidneys and salivary glands, with excess doses reportedly leading to radiotoxicity-related adverse effects, such as kidney insufficiency or xenostomia. On the basis of the triazacyclononane-triphosphinate (TRAP) chelator, monomeric to trimeric conjugates of the PSMA inhibitor motif lysine-urea-glutamic acid (KuE) were synthesized by means of Cu(I)-mediated (CuAAC) or 5-aza-dibenzocyclooctyne (DBCO)-driven, strain-promoted click chemistry (SPAAC), which were labeled with gallium-68 for application in positron emission tomography (PET), and characterized in terms of PSMA affinity (determined in cellular displacement assays against I-125-BA) and lipophilicity (expressed as log D). Using subcutaneous murine LNCaP (PSMA-positive human prostate carcinoma) xenografts, the influence of ligand multiplicity, affinity, polarity, and molar activity (i.e., mass dose) on the uptakes ...Continue Reading

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Citations

Apr 18, 2019·Organic & Biomolecular Chemistry·Longhuai ChengZhen Xi
Aug 30, 2020·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Hsiou-Ting KuoFrançois Bénard
Mar 25, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Fumihiko SoedaJun Hatazawa
Aug 18, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Viviane J TschanCristina Müller
Dec 20, 2019·Bioconjugate Chemistry·Albertus Wijnand HensbergenFijs W B van Leeuwen
Sep 21, 2021·Nanoscale Horizons : the Home for Rapid Reports of Exceptional Significance in Nanoscience and Nanotechnolgy·Tianshu ChenXiaoli Zhu

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