123I-labeling and evaluation of Ro 43-0463, a SPET tracer for MAO-B imaging.
Using the copper assisted halogen exchange the MAO-B inhibitor Ro 43-0463, N-(2-aminoethyl)-5-iodo-2-pyridinecarboxamide, was labelled with 123I as well as with 125I 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 IC50 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 micron, 250 x 8 mm) and 1.5 mL/min 0.36 M H3PO4/EtOH 97/3 [0.01 M (NH4)2HPO4]. 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 [125I]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-deprneyl the highly specific binding of R0 43-0463 was proven in vitro. SPECT studies with normal volunteers corresponded with the pattern found in autoradiography.
Paul Scherrer Institute, Radiopharmacy Division, Villigen PSI, Switzerland.
H F
HF
Beer
I
I
Rossetti
L D
LD
Frey
P H
PH
Hasler
P A
PA
Schubiger
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007553:Isotope Labeling / Q000379:methods*; D008995:Monoamine Oxidase / Q000032:analysis*; D008996:Monoamine Oxidase Inhibitors / Q000032:analysis / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D010848:Picolinic Acids / Q000032:analysis / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D007457:Iodine Radioisotopes; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D010848:Picolinic Acids; C071353:N-(2-aminoethyl)-5-iodo-2-pyridinecarboxamide; D008995:Monoamine Oxidase