Brain perfusion imaging agents

The title neutral compic.x is prepared by reduction of TcOj in saline with Sn(II) in the presence of the ligand d./-HM-PAO (hexamethyl propylene amine oxime) or, more precisely, 3,6,6,9-tetramethyl-4,8-diazaundccane-2,10-dione dioxime [40], According to structural investigations of [ Tc 0-r/,/-HM-PA() the molecular struc- 

In normal human subjects the agent allowed an excellent delineation of the cortical gray matter, the basal ganglia, the thalamus and cerebellar hemispheres as regions of relatively increased tracer uptake. White matter displayed substantially less uptake than gray matter. The primary route of excretion of the tracer is through the kidneys. TcO-L.L-E( ID I SPECr shows particular promise for the evaluation of patients with stroke [ 70], 

The activity of the agent in monkey brain 5 min post-injection was 2.8 % of the injected dose. The activity cleared with a half-life of 86 min [72], The slow cerebral clearance in human subjects may be caused by the high lipophilicity of log P = 3.8 of the agent [73 j. The testing of this complex for clinical applications in brain imaging appears to be completed now. Unfortunately, the studies in human subjects were disappointing [8.  

The ligand N-[2(l-H-pyrrolylmethyl))N -(4-pentene-3-one-2)ethane-l. 2-diaminc. called MRP-20, forms a neutral and lipophilic complex with the Tc C)- core by the loss of three protons. The compound (Fig. 6.5.B) is under investigation as a potential 

Another diaminodithiol complex with N-ethyl piperidinyl hexamethyl diaminodithiol (NEP-DADT) as the complexing ligand is rc 0(NEP-DADT)j . The agent was synthesized by reduction of Na TcOa in saline with SnCl2 2H2O in the presence of 

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Neutral technetium(ll)-99m complexes as potential brain perfusion imaging agents... 

Technetium ( Tcj Bicisate Injection. A sterile colorless solution of bicisate is complexed with Tc-99m pertech-neuite after reduction with a stannous salt. The precise structure of the technetium complex is fN,N -ethylene-di-L-cy.steinato(3-) oxo "Tc]technetium(V) diethyl ester. This radiopharmaceutical is a neutral and lipophilic complex that crosses the blotxl-brain barrier and is selectively retained in the brain. Therefore, this radiotracer is used as a brain-perfusion imaging agent. After intravenous injection of 20 mCi (740 MBq) of Tc-99m bicisate, about 5% of the injected dose is localized within the brain cells 5 minutes after injection and demonstrates rapid renal excretion (74% in 24 hours). This radiotracer is used clinically to evaluate dementia, stroke, lack of brain perfusion ("brain death"), cerebral vascular reserve, or risk of stroke (acetazolamide challenge. study) and to localize a seizure focus for surgical removal. 

To develop new brain perfusion imaging agents racemic mixtures of bis(amino-ethanethiol) (BAT) derivates containing an N -bcnzylpipcrazinyl (BPA) side chain were reacted with TcOj and 8204 to form the neutral syn and anti isomers of the Tc(V)oxo complexes. Sy -[TcO-BAT-BPA] ... 

The lipophilic complex 99mTc(IV)-L,L-ECD (62) with a deprotonated L,L-ethylcysteine dimer as ligand, is clinically used as a cerebral perfusion imaging agent. It crosses the blood-brain barrier and... 

Benzeneethanamine, 4-(iodo- l)-a-methyl-N-(1-methyl-ethyl)-, hydrochloride, ( )- ( )-p-lodo- l-N-isopropyl-a-methylphenethylamine hydrochloride lofetamine hydro-chloride l lofetamine l hydrxhioride ( l)( )-N-lsopropyl-p-iodoamphetamine hydrochloride Perfus-amine Spectamine. Lipid-soluble radioactive brain imaging agent. Crystals mp= 156-158°. 

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. 

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