I-123 LABELING AND EVALUATION OF RO-43-0463, A SPET TRACER FOR MAO-B IMAGING

Using the copper assisted halogen exchange the MAO-B inhibitor Po 43-0463, N-(2-aminoethyl)-5-iodo-2-pyridinecarboxamide, was labelled with I-123 as well as with I-125 to allow in vitro and in vivo investigations including SPET with healthy volunteers. Ro 43-0463 is known to inhibit reversibly and specifically MAO-B, having an Ic,, of 3 x 10(-8) Mol/L. The labeling in the presence of CuSO4, and ascorbic acid was optimised, varying time (30 to 105 min), precursor concentration (1-3.5 mg) and temperature (130-200 degrees C). The labeling yield ranged between 60 and 70%. Purification was achieved with Lichrosorb RP-18 (5 mu m, 250 x 8 mm) and 1.5 mL/min 0.36 M H3PO4/EtOH 97/3 [0.01 M (NH4)(2)HPO4]. After neutralisation and sterile filtration the final activity concentration ranged between 18.5 and 37 MBq/mL. Biodistribution studies showed a brain to blood ratio greater than 1 within 1 h p.i. The main radiation burden calculated from these animal data is to alimentary and excretory organs and the ovaries. Autoradiography was performed using rat brain slices and 5 nM [I-125]Ro 43-0463 in TRIS-buffer pH 7.4 for 90 min at 20 degrees C. Its radioactivity pattern corresponds to the known distribution of MAO-B in the rat brain. By displacement with L-deprenyl the highly specific binding of Po 43-0463 was proven in vitro. SPECT studies with normal volunteers corresponded with the pattern found in autoradiography.