RESUMO
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.
Assuntos
Coração/diagnóstico por imagem , Compostos Organofosforados/química , Compostos de Organotecnécio/química , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Cobaias , Masculino , Compostos Organofosforados/toxicidade , Compostos de Organotecnécio/toxicidade , Cintilografia , Ratos , Ratos Wistar , Suínos , Porco Miniatura , Distribuição TecidualRESUMO
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.
Assuntos
Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular , Oximas , Tecnécio , Tomografia Computadorizada de Emissão , Animais , Autorradiografia , Feminino , Marcação por Isótopo/métodos , Masculino , Modelos Moleculares , Oximas/síntese química , Oximas/metabolismo , Coelhos , Ratos , Ratos Endogâmicos , Estereoisomerismo , Tecnécio/síntese química , Tecnécio/metabolismo , Tecnécio Tc 99m Exametazima , Distribuição TecidualRESUMO
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.
Assuntos
Circulação Cerebrovascular , Tomografia Computadorizada de Emissão/métodos , Animais , Autorradiografia , Encéfalo/diagnóstico por imagem , Oximas , Ratos , Estereoisomerismo , Tecnécio , Tecnécio Tc 99m ExametazimaRESUMO
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).
Assuntos
Circulação Cerebrovascular , Transtornos Cerebrovasculares/diagnóstico por imagem , Tomografia Computadorizada de Emissão/métodos , Anfetaminas , Encéfalo/diagnóstico por imagem , Infarto Cerebral/diagnóstico por imagem , Humanos , Radioisótopos do Iodo , Iofetamina , Oximas , Doses de Radiação , Tecnécio , Tecnécio Tc 99m ExametazimaRESUMO
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.
