A new 99mTc-complex with a germanium-hydrazide (GeTH) ligand.

A new tetrahydrazido-germanium (GeTH) ligand was synthesized, characterized and complexed with 99mTc. The negatively charged 99mTc-chelate was shown to form in high yields at neutral pH in the absence of other reducing agents and exhibits high in vitro and in vivo stability.

99mTc-complexes of a pentadentate amine-oxime ligand.

Synthesis and characterization of a new pentadentate amine-oxime ligand, 3,3,11,11-tetramethyl-7-benzyl-4,7,10-triazatridecane-2,12- dionedioxime is reported. The technetium complexes of this ligand was formed by direct reduction of TcO4- in the presence of the ligand at pH 9. The radiochemical yield of the complex is greater than 95% with 10(-7) M 99TcO4-. The technetium complex formed is a positively charged chelate that elutes as a single peak on a reverse phase HPLC. Biodistribution studies in rats showed an uptake of 1.4% of the injected activity at 15 sec p.i. in heart, but the wash-out was fast. The high radiochemical purity and stability of this 99mTc-chelate indicate that these types of chelates hold potential for development of bifunctional chelating agents (BFCAs).

The effect of ligand structure on glutathione-mediated decomposition of propylene amine oxime derivatives.

Tetramethylpropyleneamine oxime (TMPAO) was synthesized and complexed to 99mTc. 99mTc-TMPAO samples, when challenged with reduced glutathione (GSH), were shown to have two GSH sensitive components, similar to a mixture of d,l and meso 99mTc-HMPAO. One component had a GSH-induced second-order dissociation rate constant (K2) similar to 99mTc-meso-HMPAO. Despite the presence of a large fraction of this component in these samples, brain uptake and autoradiographic studies with 99mTc-TMPAO were equivalent to 99mTc-d,l-HMPAO suggesting that both the d,l and meso 99mTc-TMPAO isomers are efficiently trapped in brain.

Synthesis, characterization and biodistribution studies of a neutral-lipophilic Tc-99m N3S2 chelate.

Diaminedithiols (DADT) are known to form neutral-lipophilic complexes with 99mTc in aqueous solutions, where they are readily formed in high yields and demonstrate excellent stability. A new triaminedithiol (TADT) ligand was synthesized, characterized and shown to form a neutral-lipophilic 99mTc-chelate. The biodistribution of this 99mTc chelate in rats showed that its uptake in brain or heart following i.v. injection of the 99mTc chelate was low, but activity taken up was retained over a long period of time. The in vivo and in vitro properties of this chelate indicate the possibility that chemical modification of this TADT ligand may produce ligand systems that form 99mTc chelates with suitable diagnostic properties.

Formation of a stable 99mTc-tri-hydrazidophosphine oxide (99mTc-THP) chelate.

Atri-hydrazidophosphine oxide (THP) ligand was synthesized and used to complex 99mTc in high yield (> 95%) by Sn(II) reduction of 99mTcO4-. 99mTc-THP has excellent stability in both 0.9% acqueous NaCl at neutral pH and in human serum at 37 degrees C. Biodistribution studies indicate minimal organ specificity and no significant in vivo release of 99mTcO4-. The ease of 99mTc complexation with THP and the high stability of 99mTc-THP suggests that this ligand may be used as a basis for the development of new imaging agents.

Evaluation of alkylated derivatives of 99mTc-propylene amine oxime (99mTc-PnAO).

Several lipophilic di-alkylated derivatives of propylene amine oxime (PnAO were complexed to 99mTc. Assessment of the 99mTc-PnAO derivatives included biodistribution and qualitative autoradiography. All of the derivatives studied penetrated the intact blood-brain-barrier, with the 99mTc-dibutyl-PnAO complex exhibiting the lowest initial brain uptake while the 99mTc-diethyl-PnAO and the 99mTc-dipropyl-PnAO complexes possessing nearly identical initial brain uptake as compared to 99mTcPnAO. Qualitative autoradiographs revealed significant loss of image resolution with extended time post injection indicative of rapid radiopharmaceutical washout. Although increasing alkyl chain length did not enhance initial brain uptake, the data demonstrates that limited modification of the PnAO ligand structure can be performed without decreasing cerebral uptake of the respective 99mTc complex.

Sensitivity of technetium-99m-d,1-HMPAO to radiolysis in aqueous solutions.

The sensitivity of technetium-99m- (99mTc) d,l-HMPAO to radiolytically induced dissociation in aqueous solutions was investigated. It was found that cobalt-60 (60Co) gamma irradiation of solutions containing 99mTc-d,l-HMPAO with only 1600 cGy reduced the lipophilic chelates' radiochemical purity (RCP) to 50%-60%. The radiolytic sensitivity of 99mTc-meso-HMPAO is significantly lower. The results indicate that radiolytically produced intermediates limit the in vitro stability of 99mTc-d,l-HMPAO.

Biolocalization and cell labeling properties of neutral-lipophilic 99mTc-amine-phenol chelates.

99mTc-diamine-diphenol chelates are neutral lipophilic chelates exhibiting good stability in aqueous solutions. The cell labeling and biolocalization properties of four different 99mTc-amine-phenol complexes were determined. All four chelates readily labeled leukocytes and RCBs in high yields. Even though 99mTc was retained by the cells, the elution rate of 99mTc from the labeled cells in plasma at 37 degrees C was unacceptably high for potential utility in scintigraphic imaging. The uptake of 99mTc in brain or heart following i.v. injection of the chelates in rats was low and clearance of activity from the blood was slow.

Retention of [99mTc]-d,l-HM-PAO in rat brain: an autoradiographic study.

The regional cerebral distribution pattern of [99mTc]-d,l-HM-PAO in rat brain was studied by autoradiography. The regional cerebral uptake of this tracer is related to regional cerebral blood flow (rCBF); however, the ratio of retained radioactivity (determined by digital imaging techniques) in gray matter compared to white matter is lower than that reported for the blood flow ratio. Considerable inhomogeneity is observed in cortical gray matter for at least 60 min postinjection, demonstrating that minimal, if any, cerebral redistribution of this agent occurs.

Kinetic analysis of technetium-99m d,1-HM-PAO decomposition in aqueous media.

Technetium-99m-d,1-hexamethylpropyleneamine oxime [99mTc]d,1-HM-PAO) is a neutral-lipophilic chelate formed from a kit in high yield by stannous reduction of Na99mTcO4-. Of three methods used to analyze the purity of the 99mTc complexes, a single strip method using ether as the developing solvent was the most rapid and simple to perform. The lipophilic chelate converts to 99mTcO4- and other hydrophilic products with time and this limits the useful lifetime of the preparations. The rate of decomposition of [99mTc]d,1-HM-PAO increased in the presence of excess stannous ion and at pH greater than 9.