Positron emission tomography (PET) in conjunction with C15O2 or H215O can be used to measure myocardial blood flow (MBF) and tissue fraction (TF), i.e. the fraction of the tissue mass in the volume of the region of interest. However, with C15O2 inhalation, the tissue fraction in the septum is overestimated. Bolus injection of H215O together with arterial cannulation gives very precise results but is invasive. The purpose of this study was to develop a method which circumvents these problems. A four-parameter model with parameters for MBF, TF and spill-over fractions from both left and right ventricular cavities was developed. This method was compared with a three-parameter model (no right ventricular cavity spill-over) in both septal and non-septal regions of interest for three different administration protocols: bolus injection of H215O, infusion of H215O and inhalation of C15O2. It was found that MBF can be measured with intravenous administration of H215O without the requirement for arterial cannulation. The four-parameter protocol with bolus injection was stable in clinical studies. The four-parameter model proved essential for the septum, where it gave highly significantly better fits than did the three-parameter model (P<0.00003 in each of 15 subjects). Administration of H215O together with this four-parameter model also circumvented the problem of overestimation of TF in the septum seen with C15O2 inhalation. In addition, the radiation dose of H215O protocols is lower than that of C15O2 inhalation. Using a left atrial input curve instead of a left ventricular cavity input curve gave the same mean MBF and TF.

The production of Tc-94m as pertechnetate, a t(1/2) = 53 min positron emitter, was studied with small and medium energy cyclotrons. At a proton energy of 11 MeV, the irradiation of natural molybdenum provides adequate saturated yields (3 mCi/mu A) with tolerable radionuclidic purity for radiopharmaceutical investigations in man. The longer lived Tc-95, Tc-95m and Tc-96 isotopes can be virtually eliminated by irradiating an isotopically-enriched (MoO3)-Mo-94 target. In a study of alternative entrance channels leading to Tc-94m, natural niobium and molybdenum targets were irradiated with He-3 and He-4 beams. The goal was to reach pure Tc-94m through the Ru-94/Tc-94m generator system, bypassing contamination by the Tc-94g ground state.

Models based on uniform distribution of tracer in total body water underestimate the absorbed dose from H215O because of the short half-life (2.04 min) of 15O, which leads to non-uniform distribution of absorbed dose and also complicates the direct measurement of organ retention curves. However, organ absorbed doses can be predicted by the present kinetic model based on the convolution technique. The measured time course of arterial H2150 concentration following intravenous administration represents the input function to organs. The impulse response of a given organ is its transit time function determined by blood flow and the partition of water between tissue and blood. Values of these two parameters were taken from the literature. Integrals of the arterial input function and organ transit time functions were used to derive integrals of organ retention functions (organ residence times). The latter were used with absorbed dose calculation software (MIRDOSE-2) to obtain estimates for 24 organs. From the mean values of organ absorbed doses, the effective dose equivalent (EDE) and effective dose (ED) were calculated. From measurements on 21 subjects, the average value for both EDE and ED was calculated to be 1.2 μSv · MBq−1 compared with a value of about 0.5 μSv · MBq−1 predicted by uniform water distribution models. Based on the human data, a method of approximating H215O absorbed dose values from body surface area is described.

S-[1-(2,3-Diaminophenoxy)]-3′-(N-t-butylamino)propan-2′-ol has been synthesized in three steps from 2,3-dinitro-phenol and the chiral auxiliary, S-glycidyl-3-nitrobenzenesulphonate, to provide a precursor for labelling S-(3′-t-butylamino-2′-hydroxypropoxy)-benzimidazol-2-one (S-CGP 12177) with the short-lived positron-emitting radionuclide, carbon-11 (t12 = 20.4 min; β+ = 99.8%). Reaction of the diamine with [11C]phosgene, itself derived from no-carrier-added cyclotron-produced [11C]methane, provides radiochemically and chemically pure S-[carbonyl-11C]CGP 12177 in95% enantiomeric excess after HPLC. Automated apparatus is described for safely producing up to 5.9 GBq (160 mCi) of S-[11C]CGP 12177 with high sp. act. (20–40 GBq/μmol or 0.54–1.08 Ci/μmol) in a form suitable for human intravenous injection at only 30 min from the end of radionuclide production. S-[11C]CGP 12177 is preferred to the formerly described racemate as a radioligand for the study of β-adrenergic receptors in vivo by positron emission tomography.

Data for the production of fluorine-18 (t1/2 = 109.6 min; β+ = 100%) are reviewed. The experience of some well-established European centres for positron emission tomography (PET), in the routine production of fluorine-18 for the purpose of labelling radiopharmaceuticals, is described. This experience is evaluated, along with published data, to give practical and technical recommendations to new PET group entering this key area.