68Ga-Complex Lipophilicity and the Targeting Property of a Urea-Based PSMA Inhibitor for PET Imaging

• DOI: 10.1021/bc200279b
• Publication Date: 2012-02-28T06:06:35Z
• Authors: Matthias Eder; Martin Schäfer; Ulrike Bauder-Wüst; William-Edmund Hull; Carmen Wängler; Walter Mier; Uwe Haberkorn; Michael Eisenhut
• Keywords: Conjugate; Biodistribution; Internalization; Lipophilicity; Glutamate carboxypeptidase II; DOTA

Urea-based inhibitors of the prostate-specific membrane antigen (PSMA) represent low-molecular-weight pepidomimetics showing ability to image PSMA-expressing prostate tumors. The highly efficient, acyclic Ga(III) chelator N,N'-bis [2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-N,N'- diacetic acid (HBED-CC) was introduced as a lipophilic side chain into hydrophilic pharmacophore Glu-NH-CO-NH-Lys which found favorable interact with PSMA "active binding site". This report describes syntheses, in vitro analyses, and biodistribution data radiogallium labeled inhibitor Glu-NH-CO-NH-Lys(Ahx)-HBED-CC comparison corresponding DOTA conjugate. properties were analyzed using competitive cell enzyme-based assays followed by internalization experiments. Compared DOTA-conjugate, HBED-CC derivative showed reduced unspecific considerable higher specific LNCaP cells. (68)Ga complex ligand exhibited specificity for expressing tumor cells resulting improved vivo properties. fast blood organ clearances, low liver accumulation, high uptake organs tumor. It could be demonstrated that PET-imaging property urea-based significantly HBED-CC.