Perfusion agent

Fig. 3. Structures of myocardial perfusion agents (a) Tc(I)(MIBI)g -sestamibi), where MIBI = 2-methoxyisobutylisonitrile (b)...

Certain neutral technetium complexes can be used to image cerebral perfusion (Fig. 4). Those in Figure 4a and 4b have been approved for clinical use. Two other complexes (Fig. 4c and 4d) were tested in early clinical trials, but were not developed further. An effective cerebral perfusion agent must first cross the blood brain barrier and then be retained for the period necessary for image acquisition. Tc-bicisate is retained owing to a stereospecific hydrolysis in brain tissue of one of the ester groups to form the anionic complex TcO(ECD) , which does not cross the barrier. This mechanism of retention is termed metaboHc trapping. 

Fig. 4. Structures of cerebral perfusion agents (a) Tc(V)0(HMPA0) ( " Tc-exametazine [103613-48-7]), whem...

Technetium-99m tetrafosmin ( Tc-(V)02 (l,2-bis(bis(2-ethoxyethyl)phosphino)ethane) (see Fig. 3d)) is a myocardial perfusion agent. It is used as an adjunct in the diagnosis and localization of myocardial ischemia and/or infarction. 

Great interest in diphosphino complexes of technetium arose when Deutsch and co-workers found that lipophilic cations are able to be accumulated in heart tissue and can thus be candidates for myocardium perfusion agents [120]. Both the Tc(V) DMPE complex, [Tc02L2]+, and the [TcL2X2] + and [TcL3] + species in oxidation states +3 and +1 have been evaluated. Whereas the [Tc02L2] +... 

Myoview 99mTc-tetrofosmin (67) is another clinically approved, lipophilic, cationic perfusion agent (286). The molecule contains trans-... 

Recently, a family of monocationic complexes of the type [M(N)(P-N-P)-(S2CNR1R2)]+, which exhibit high myocardial uptake in rats, was also described [51,52]. Some of these complexes possess superior biological properties, compared with Sestamibi and Tetrafosmin. However, because of the possibility of species-dependent effects, further studies of these agents in other animal models are underway, in order to assess their utility as heart perfusion agents [52]. 

Heart Agents. Routine myocardial perfusion imaging in nuclear medicine started with ° T1 thallous chloride. While ° T1+ is efficiently perfused into the myocardium, the long half-life and imaging characteristic s are not optimal for nuclear medicine imaging and cationic Tc-based perfusion agents were desired. 

Other lipophilic cations that have been approved as myocardial perfusion agents include a Tc(III) Tc-teboroxime cryptate, (Cardiotec ), the trans-dioxo technetium(V) bis-phosphine complex, "Tc-tetrofosmin (Myoview ) and the mixed ligand Tc(III) Schiff-base bisphosphine Tc-Q12 complex, Tc-furifosmin (TechneScan) (Figure 3). 

A continuous search for the Tc-99m myocardial perfusion agents is carried out, based on the assumption that various monovalent cations K, Rb , Cs " and Ti as well as singly charged organic cations accumulate preferentially in the myocardium. Deutsch and coworkers synthesized nineteen cationic Tc-99m complexes (equation 83) and evaluated them as myocardial imaging agents in dogs. All phosphine, arsine and thiol... 

Although the chemistry of barbiturates has been explored for a very long time, these compounds still attract the attention of chemists, as exemplified by a recently published synthesis for 157 as a potential cerebral perfusion agent for tomography574 or by studies of the chemical and metabolic degradation of 158.575 However, it is the medicinal application of barbiturate drugs and... 

These complexes are well modified in the backbone, without decreasing the complex stability. Q12 is the best derivative in the series (Deutsch et al. 1987) however, none of these ligands has been used as a myocardial perfusion agent. 

Dioxime type ligands can be considered as Schiff base bischelates (Deutsch et al. 1978 Bandoli et al. 1986). The first complexes with oxime ligands were described as mono-capped Tc(dioxime)3(//OH)SnCl3 (dioxime = dimethylglyoxime) complexes (Treher et al. 1989). The boronic adducts of technetium oximes - (BATOs) (Fig. 2.1.19) - were well characterized, and some could be used both as myocardial and cerebral perfusion agents. The complexes are neutral technetium is coordinated to three N-bonded dioxime molecules and to one Cl or Br atom in an axial position (seven covalent bonds). 

Cagnolini A, Whitener D, Jurisson S (1998) Comparison of the kit performance of three " Tc myocardial perfusion agents. Nucl Med Biol 25 435-439 Carvalho PA, Chiu ML, Kronauge JF, Kawamura M, Jones AG, Holman BL, Piwnica-Worms D (1992) Subcellular distribution and analysis of technetium-99m-MIBI in isolated perfused rat hearts. J Nucl Med 33 1516-1522... 

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