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- Document type:
- Journal Article
- Author(s):
- Schmidt, Alexander; Wirtz, Martina; Färber, Stefanie Felicitas; Osl, Theresa; Beck, Roswitha; Schottelius, Margret; Schwaiger, Markus; Wester, Hans-Jürgen
- Title:
- Effect of Carbohydration on the Theranostic Tracer PSMA I&T.
- Abstract:
- To investigate the effect of carbohydrate moieties on the pharmacokinetic profile of prostate-specific membrane antigen (PSMA) inhibitors, carbohydrated derivatives of the established PSMA-targeted radiopharmaceutical PSMA I&T were developed and evaluated. As observed for the reference PSMA I&T, the natGa/natLu complexes of the respective galactose-, mannose-, and cellobiose-conjugated analogs showed high PSMA affinity. Carbohydration had almost no effect on the lipophilicity, whereas PSMA-mediated internalization was reduced. The specific binding toward human serum albumin (HSA) decreased from 78.6% for [natLu]PSMA I&T to 19.9% for the natLu-labeled cellobiose derivative. Compared to [68Ga]PSMA I&T, [68Ga]PSMA galactose displayed lower nonspecific tissue and kidney accumulation but also slightly lower tumor uptake in small-animal positron emission tomography (μPET) imaging. Biodistribution studies confirmed reduced unspecific uptake in nontarget tissue and decreased renal accumulation of the metabolically stable [68Ga]PSMA galactose derivative, resulting in overall improved tumor-to-tissue ratios. However, carbohydration has no significant beneficial in vivo effect on the targeting performance of PSMA I&T. Nevertheless, carbohydration expands the repertoire of feasible modifications within the linker area and might be a valuable tool for the future development of PSMA inhibitors with decreased kidney uptake.
- Journal title abbreviation:
- ACS Omega
- Year:
- 2018
- Journal volume:
- 3
- Journal issue:
- 7
- Pages contribution:
- 8278-8287
- Fulltext / DOI:
- doi:10.1021/acsomega.8b00790
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/30087939
- TUM Institution:
- Klinik und Poliklinik für Nuklearmedizin
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