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 autoradio-graphic 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 (T½ 20.4 min) was produced by the (p,α) nuclear reaction on 14N. 11C-methyl iodide was used to methylate 3-methyl-l-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 ICDE in man by commision comography.