SPECT radiopharmaceuticals

Fig. 26. Chemical structure of f llMIBG, a single photon emission computed tomography (SPECT)-radiopharmaceutical for cardiac neuronal imaging, and its lead structure guanethidine.

The potent dopaminergic D-l receptor-binding ligand467,468 334 has been synthesized469 by NCA electrophilic iododeprotonation of the precursor SKF 83692 (equation 218). 334 has been employed as a SPECT radiopharmaceutical and for the production of its [125I]... 

SPECT uses radionuclides, such as tedmetium-99m, rather than positron-emitters, such as carbon-11 or fluorine-18, as is the case with PET. A widely used SPECT radiopharmaceutical is technetium-99m hexamethylpropylene amine oxime, to measure regional cerebral blood flow after systemic administration of the cerebral vasodilator acetazolamide (aceta-zolamide test) to patients with Alzheimer s disease (AD) or vascular dementia (VD). 

PET imaging systems are somewhat more complex, and therefore more expensive than are SPECT systems, and the price factor is generally between two and three. The primary cost premium associated with these systems, however, is the need for a cyclotron and its attendant staff combined with the relative complexity of radiopharmaceutical preparation for short half-life isotopes. As of 1996, there are considerable hurdles blocking widespread regulatory approval and full reimbursement of PET studies. 

PET has been gaining in popularity as a result of its enhanced sensitivity and resolution with respect to SPECT at the millimetre scale, allowing clinicians to study drug distribution in vivo (10). Indeed, it is estimated that by 2010 there will be approximately two million PET scans per year, of which the majority will image the metabolism of the 18F-labeled fluoro-deoxyglucose (FDG) (11). The increased sensitivity in turn reduces the concentration of the administered radiopharmaceutical required to 10 8-10 10M. The much lower concentrations of administered radioactive probe employed reduce the overall... 

Another class of commonly used radiopharmaceuticals measure regional brain blood flow. In PET, [ 0]H20 is used as a radiopharmaceutical and in SPECT, [99mjc]HMPAQ, [99> Tc]ECD, or [ 9 ] /]p are used. Studies of patients with AD with the use of these radiopharmaceuticals have been thoroughly reviewed elsewhere [e,g, 34-36] and it is out of the scope of this chapter to further discuss these studies. 

Since emission tomography requires some type of internal radioactive sources, a large number of radionuclides have been developed and produced specifically for these applications. Gamma emitters are used for SPECT, while positron emitters are used for PET. The chemical form of a radionuclide is tailored specifically for a given target (tissue, bone, or organ). Compounds labeled with radionuclides for administration to patients are known as radiopharmaceuticals. 

PET radiopharmaceuticals offer enhanced spatial resolution and quantification capabilities compared with SPECT agents. To probe Pgp transport activity, PET-based radiopharmaceuticals have been actively investigated on three fronts (1) use of SPECT scaffolds capable of accommodating PET radionuclides, (2) bioinorganic radiochemistry, and (3) conventional PET organic radiochemistry. 

Nakajima, K. Shuke, N. Taki, J. Ichihara, T. Motomura, N. Bunko, H. Hisada, K. A simulation of dynamic SPECT using radiopharmaceuticals with rapid clearance. J. Nucl. Med. 1992, 33 (6), 1200-1206. 

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