Where have we got to with neuroreceptor mapping of the human brain?

Abstract

In the past two decades, tritiated radioligand receptor binding, a tool commonly used to investigate the site of action of drugs in laboratory animals, has provided a vast body of information on neuropharmacology and neurobiology. Several neurological and psychiatric diseases have been related to neurotransmitter and receptor disorders. In order to study ligand interactions with receptors in vivo in humans, new tracers capable of carrying a gamma-emitting radionuclide to the receptor have been designed. Emission computerized tomography (ECT) techniques such as positron (PET) or single photon emission tomography (SPET) allow monitoring of the time-course of regional tissue concentration of these radiolabelled ligands. PET and SPET each have their inherent advantages and drawbacks. The cyclotron-based technology of PET is a demanding and expensive technique that, to date, is still mainly reserved for research purposes. It is hoped that once the scientific basis of a physiopathological study is established using PET, diagnostic information might be provided by the more readily available SPET technology. The purpose of this article is to review the current state of receptor-binding gamma-emitting radioligands and to present the clinical potential of these new kinds of radiopharmaceuticals in clinical investigation.

New Approaches to Imaging Based on Effects of Neurotoxins

“…A number of studies have described muscarinic agents which may be used in PET and SPECT studies [17][18][19], Yet few attempts have been made to visualize muscarinic receptors in the brains of AD patients, and the ligands used are unsuitable to distinguish different receptor subtypes. Recent attempts to distinguish subtypes using [' 'Cjmethylbenztropine have been more successful [20] Values are mean specific fmol/mg tissue equivalent bound ± SEM on ipsilateral side and contralateral side in medial Frl/Fr2 and lateral Parl/Par2 areas, following injection of 2 ng volkensin (n = 6), 10 ng ricin (n = 5) or 10 pg quinolinate (n = 6) into the striatum.…”

Pharmacological implications for neuroreceptor imaging

“…a loss in the caudate nucleus (Reisine 1981). These receptors can also now be studied with PET (Mazi6re and Mazi6re 1990) and probably will be studied with SPET (Wilson et al 1990b). Thus nuclear medicine will provide the tools for studying in vivo the alterations in both striatal D2 and opiate receptors, which may be directly linked in this brain region (Reisine 1981), and its significance in the pathophysiology of opioid addiction and schizophrenia.…”

“…The state of the art of neuroreceptor imaging in nuclear medicine has recently been discussed in this journal (Mazi6re and Mazi6re 1990). Several of the radioligands now available for in vivo imaging and some of the characteristics of the receptors to which they bind are mentioned in Tables 1 6.…”

Initial experience with single-photon emission tomography using iodine-123-labelled 2 ?-carbomethoxy-3?-(4-iodophenyl)tropane in human brain

“…Thus, a suitable radiomarker of the dopamine uptake and/or re-uptake site would be of clinical interest in neurology and psychiatry for in vivo measurements of the human dopaminergic system. Most such studies in Parkinson's disease have been done with positron emission tomography (PET) [3,4]. However, several receptor imaging agents labelled with radioactive iodine-123 for singleCorrespondence to: J.T.…”