MAO-A ENZYME BINDING IN BLADDER-CANCER CHARACTERIZED WITH [C-11] HARMINE IN FROZEN-SECTION AUTORADIOGRAPHY

Operative specimens from 7 patients with urinary bladder cancer and with only inflammatory tissue in the operative sample from one patient, were used for frozen section autoradiography using [C-11]harmine to characterize the expression of the enzyme monoamine oxidase A (MAO-A). Tissue sections (25 mu m thick) were incubated with [C-11]harmine at concentrations of 2 and 10 nM for 45 minutes, washed and exposed on a phosphor imaging plate system. Rat brain sections were included in each experiment and used as a standard to which the binding in the tumor sections were related. Non-specific binding was estimated by incubation in the presence of 1 mu M harmine. Displacement experiments were performed with both harmine and clorgyline. Good visualization was obtained in all tumor and rat brain samples, although several tumor samples included areas with variable binding. Quantitatively, the binding in the tumor samples was on the average 1.4 times that of rat brain (range 0.4-3.3); One section with only inflammatory cells had a ratio of 0.08, and in one specimen from a patient given preoperative chemotherapy, the ratio was -0.1. Binding inhibition experiments demonstrated an IC50 of approximately 5 nM for harmine and approximately 10 nM for clorgyline. These results indicate that specimens from urinary bladder cancer have a high expression of the enzyme MAO-A. With the availability of [C-11]harmine and positron emission tomography (PET) it is reasonable to believe that in vivo characterization of MAO-A in bladder cancer is feasible and could be used for diagnostic purposes or for treatment monitoring. The physiological significance of the high expression of MAO-A in bladder cancer remains to be elucidated.