11C-Iodoantipyrine for the measurement of regional cerebral blood flow by positron emission tomography. Validation studies

Positron emission tomography (PET) makes it possible to employ an in vivo autoradiographic paradigm to measure regional cerebral blood flow (rCBF) in man. In this study, we synthesized the positron-emitting radiopharmaceutical 11C-iodoantipyrine (11C-IAP) and validated its suitability as a CBF tracer. 11C ( T and one-half 20.4 min) was produced by the (p,alpha) nuclear reaction on 14N. 11C-methyl iodide was used to methylate 3-methyl-1-phenyl-2-pyrazolin-5-one to form 11C-antipyrine, which was iodinated. Radiochemical purity of the 11C-IAP product was 93-98% except as described below. rCBF was measured with 11C-IAP in nitrous oxide-anesthetized Wistar rats by the method of indicator fractionation, and values were compared with rCBF values measured with simultaneously administered commercially produced 14C-IAP. rCBF was studied over a range of arterial Pco2 values (31-58 mm Hg, mean 43.0 +/- 3.5). Mean rCBF data for the 2 tracers agreed to within 4.8% for cerebral hemispheral samples, 3.8% for cerebellum, and 5.3% for brainstem. Mean values (+/- SEM) for rCBF using 11C-IAP were 1.67 +/- 0.20 ml gm-1 min-1 for cerebral hemispheres; 1.32 +/- 0.17 for cerebellum; and 1.50 +/- 0.21 for brainstem. When chromatographic analysis revealed tracer impurity, rCBF, as measured with 11C-IAP, fell consistently below values obtained with 14C-IAP. The data indicate that 11C-IAP, when properly synthesized and submitted to batch-by-batch quality control, may be suitable for measuring rCBF in man by emission tomography