Jorma Hassfeld

Radiofluorinated derivatives of 2-(phosphonomethyl)pentanedioic acid as inhibitors of prostate specific membrane antigen (PSMA) for the imaging of prostate cancer.

For prostate cancer, prostate specific membrane antigen (PSMA) has been identified as a diagnostic and therapeutic target. Fluorinated derivatives of 2-(phosphonomethyl)pentanedioic acid were designed and synthesized to explore whether this fluorine-substituent is tolerated in the pentanedioic acid moiety that is common to almost all PSMA targeting small molecule inhibitors. The binding affinities of the racemic and individual stereoisomers of 2-fluoro-4-(phosphonomethyl)pentanedioic acid were determined and showed that the introduction of fluorine was well tolerated. The radiosynthesis of the analogous 2-[(18)F]fluoro-4-(phosphonomethyl)pentanedioic acid was developed and evaluated in vivo with the PSMA positive LNCaP human prostate cancer cell. The biological results demonstrated specific binding of the tracer to PSMA positive tumors in mice. These results warrant the further evaluation of this class of compounds as radiolabeled tracers for the detection and staging of prostate cancer.

New Tungsten Cluster Based Contrast Agents for X-ray Computed Tomography

In recognition of the seminal contributions of F. A. Cotton and A. Bino to the field of aqueous chemistry of organometallic, trinuclear cluster compounds of tungsten, we describe their modifications and use as contrast agents for X-ray computed tomography. To enable their fundamental work for an advantageous diagnostic application in medicine a new generation of polydentate W3O2 complexes with improved hydrolytical stability has been synthesized and characterized. The applicability as new metal based contrast agent has been demonstrated in a computed tomography angiography animal study with increased signal intensity. Especially the bis tridentate W3O2 complexes with their reduced stereochemical complexity represent a promising new class in the field of X-ray contrast agents.