How to Study Smoking and Drinking with PET

The era of imaging neuroreceptors in humans with PET was ushered in by Wagner et al. (1983) with a report in Science showing the first human brain scan of dopamine receptors (Wagner, 1983). The tracer was N-methylspiperone (NMSP) tagged with carbon-11. The brain that was scanned belonged to one of the authors. Ethical concerns notwithstanding, this act placed the researchers in the good company of famous scientists throughout history who had experimented on themselves. The publication of this paper excited the field and garnered some publicity as well (see Figure 1). Although the study did not employ the quantitative analysis techniques we describe below, it presaged some of the key concepts. Namely: (1) early images contain mostly blood flow information; (2) late images primarily reflect binding; (3) radioactive tracer in the target tissue can be “free” or “bound”, which often necessitates the examination of a “reference region”, which is devoid of receptor sites; (4) co-injection of radiolabelled tracer with an excess of unlabeled tracer can be used to prevent radiotracer from binding and thus measure unbound (aka, non-displaceable) signal by itself. Injection of excess unlabeled tracer is generally not performed in humans; in this case, it was done in baboons. As we discuss below, the ability to use PET to measure receptor number or some index thereof opens up additional measurement possibilities which take advantage of a key concept: competition. In the Wagner paper, the competition was between hot (labeled) and cold (unlabeled) tracer (Wagner, 1983). In another ground-breaking paper that followed it, the competition was between a radiotracer and an unlabeled neuroleptic drug (Farde et al., 1986). Farde and colleagues did what amounts to the first drug occupancy study with PET using the tracer, [11C]raclopride, in 1986. Their paper was intended to examine the occupancy level of drugs for schizophrenia in treated schizophrenics by examining the degree of tracer blocking at the dopamine D2 receptor sites achieved by each patient’s respective drug. Whereas Wagner et