Novel Metalloporphyrins as Molecular MR Contrast Agents

Introduction: To date, no imaging methodology exists which can image prostate cancer in vivo with sufficient sensitivity and specificity for diagnostic utility. As a consequence, urological surgeons and oncologists proceed with treatment strategies based on ‘blind’ biopsy tissue specimens and limited diagnostic evaluations using conventional MRI and ultrasound. In these experiments, we have investigated a new class of therapeutic metalloporphyrins for their potential as molecular MR imaging probes for prostate cancer detection. Mn(III)TE-2-Pyp (meso-tetrakis(N-ethyl-2prydil)porphyrin) and Mn(III)TnHex-2-PYP (meso-terakis(N-n-hexyl-2-pyridyl)porphyrin are powerful superoxide dismutase mimics with low toxicity and antineoplastic activity . In phantom experiments, we observe unusually high T1 relaxivity with these compounds that is several-fold greater than commercially available gadolinium chelates (Magnevist, Prohance.) Observable detection limits are in the low micromolar range at 7 Tesla. In vivo, we observe selective accumulation of these probes in prostate tumor xenografts following a single dose of either compound. Relaxation changes in prostate tumors is 10-11 fold greater than in normal prostate gland, suggesting these compounds may be particularly effective at selectively detecting multifocal disease in situ.