ABSTRACT
A new cationic complex, [99mTc(tetrofosmin)2O2]+, where tetrofosmin is the ether functionalized diphosphine ligand 1,2-bis[bis(2-ethoxyethyl)phosphino]ethane, has been synthesized and evaluated for potential use in myocardial perfusion imaging. The structure of the complex has been determined by x-ray crystallography of the 99Tc analog. In comparison with previously reported 99mTc complexes of alkyl-phosphines, the tetrofosmin species shows substantially increased clearance from nontarget tissue, especially blood and liver. A freeze-dried kit formulation has been developed. The kit provides a product of high radiochemical purity up to 8 hr after reconstitution at room temperature.
Subject(s)
Heart/diagnostic imaging , Organophosphorus Compounds/chemistry , Organotechnetium Compounds/chemistry , Animals , Chromatography, High Pressure Liquid , Female , Guinea Pigs , Male , Organophosphorus Compounds/toxicity , Organotechnetium Compounds/toxicity , Radionuclide Imaging , Rats , Rats, Wistar , Swine , Swine, Miniature , Tissue DistributionABSTRACT
Following investigation of a large number of new ligands based upon propylene amine oxime (PnAO) the d,l-diastereoisomer of hexamethyl propyleneamine oxime (HM-PAO) was selected as the preferred ligand for 99mTc as a tracer for cerebral perfusion imaging. The neutral, lipophilic 99mTc complex of d,l-HM-PAO was formed in high yield by stannous reduction of 99Mo/99mTc generator eluate using a kit formulation of the ligand. Two minutes following i.v. administration of this complex in rats, 2.25% of the injected dose appears in the brain. Little washout of the tracer is observed up to 24 hr postinjection. By qualitative autoradiographic comparison with iodoantipyrine this new radiopharmaceutical displays blood flow dependent brain uptake with little redistribution of the tracer over time. The lipophilic 99mTc complex converts slowly in vitro to a secondary complex. This conversion process may account for the ability of [99mTc]d,l-HM-PAO to be retained within the brain without redistribution.
Subject(s)
Brain/diagnostic imaging , Cerebrovascular Circulation , Oximes , Technetium , Tomography, Emission-Computed , Animals , Autoradiography , Female , Isotope Labeling/methods , Male , Models, Molecular , Oximes/chemical synthesis , Oximes/metabolism , Rabbits , Rats , Rats, Inbred Strains , Stereoisomerism , Technetium/chemical synthesis , Technetium/metabolism , Technetium Tc 99m Exametazime , Tissue DistributionABSTRACT
A new radiopharmaceutical, 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HM-PAO) has shown considerable promise for single photon emission tomographic (SPECT) imaging of the brain. In animal biodistribution studies this complex demonstrates good brain uptake with prolonged retention of activity in brain. Further improvement of these properties, resulting in higher brain uptake with very slow washout and fixed regional distribution has been achieved following the isolation of the d,1-diastereoisomer of HM-PAO.
Subject(s)
Cerebrovascular Circulation , Tomography, Emission-Computed/methods , Animals , Autoradiography , Brain/diagnostic imaging , Oximes , Rats , Stereoisomerism , Technetium , Technetium Tc 99m ExametazimeABSTRACT
The first clinical data is given on 99Tcm-hexamethylpropyleneamine oxime (HM-PAO) in normal subjects and patients with established stroke. Regional cerebral blood flow maps (rCBF) have been recorded and displayed in tomographic mode with this new radiopharmaceutical. Good images were obtained, comparable to those achieved with 123I-isopropylamphetamine (IMP).
Subject(s)
Cerebrovascular Circulation , Cerebrovascular Disorders/diagnostic imaging , Tomography, Emission-Computed/methods , Amphetamines , Brain/diagnostic imaging , Cerebral Infarction/diagnostic imaging , Humans , Iodine Radioisotopes , Iofetamine , Oximes , Radiation Dosage , Technetium , Technetium Tc 99m ExametazimeABSTRACT
A new radiopharmaceutical, 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HM-PAO) is described. This agent displays considerable promise for imaging cerebral blood flow. In studies in rats and one human volunteer, 99Tcm-HM-PAO demonstrates good brain uptake, prolonged retention of activity in the brain, and slow regional redistribution. These properties suggest that this new radiopharmaceutical is ideal for single photon emission tomographic (SPECT) imaging of cerebral blood flow.
