David E. Troutner

99mTc-propylene amine oxime (99mTc-PnAO); a potential brain radiopharmaceutical

Propylene amine oxime (PnAO) forms a neutral lipid soluble complex with 99mTc. 99mTc-PnAO can be prepared by simple reduction of 99mTc-pertechnetate with stannous ion in the presence of excess PnAO in saline at or near neutral pH. This agent will passively penetrate biological membranes including the intact blood-brain barrier (BBB) as evidenced by the high brain uptake observed shortly after IV injection. The first-pass extraction efficiency in baboons was estimated to be 80% at normal blood flow. This agent or a derivatized form of 99mTc-PnAO may be useful in assessment of regional cerebral blood flow (rCBF) in humans.

Labeling of amine ligands with 99mTc in aqueous solutions by ligand exchange

Abstract Cyclam, ethylenediamine (EN) and a linear tetraamine (TA) form structurally similar complexes in high yields when pertechnetate is reduced with Sn(II) in aqueous alkaline solutions. Efficient labeling of these amine ligands is also accomplished by transfer of 99mTc from its complexes with diethylenetriaminepentaacetate (DTPA) and citrate. The labeling yields of cyclam, TA and EN using [99m Tc]DTPA are greater than 95% after standing for 30 min at room temperature in 0.03 M solutions of the amine ligands at pH above 11, but less than 10% at pH below 9. Yields of greater than 90% are obtained using [99mTc]citrate under similar conditions at pH 7 or greater. Ethylenediamine-N,N-diacetic acid (ENDA) also forms a complex with 99mTc that exhibits pH dependent stability characteristics that are the same as those of [99mTc]EN. The labeling efficiency of ENDA with 99mTc as a function of pH is nearly identical to that of the other amine ligands.

153Sm radiotherapeutic bone agents

Samarium-153 is a radionuclide which can be produced in high yield by neutron irradiation and which has nuclear properties that make it attractive for use as a radiotherapeutic agent. Several phosphonate complexes of 153Sm were synthesized and characterized by electrophoresis and HPLC. A procedure based on cation exchange chromatography was developed for measuring complex yields. The complexes could be produced in yields greater than 99%, were anionic, and most exhibited a single HPLC peak.

Chemical and physical properties of radionuclides

There are many radionuclides with a wide range of energies and half-lives available for use as non-sealed radiotherapeutic agents. To date, no single radionuclide has emerged as being clearly superior to all others, in the way that 99mTc predominates in diagnostic imaging. It is unlikely that one will emerge. Instead, if a particular application demands certain decay properties, the radionuclide which will be used will be the one for which appropriate chemistry can be developed and which can be produced and distributed most economically.

Radiochemical studies of technetium complexes of tetradentate amine-phenols

We have synthesized amine-phenol ligands of the general structure bis-(2-hydroxybenzylamino)X, where X is a hydrocarbon backbone. Radiochemical studies of 99Tc and 99mTc complexes were done at total technetium concentrations of 0.1–100 μM. Complex yields were measured by ascending solvent paper chromatography, TLC, solvent extraction and reversed phase HPLC. Complexes were readily formed and were neutral and lipophilic. Lipophilicity was enhanced by the addition of methyl groups to the carbon backbone. Similar complexes formed from the corresponding Schiff base ligands were less lipophilic and were formed in lower yields.

Reversed-phase HPLC of [99mTc]tetraamine complexes

Abstract Radiochemical purity of a variety of cationic [99mTc]tetraamine complexes can be conveniently determined by reversed-phase high performance liquid chromatography (HPLC) using styrene-divinylbenzene as the stationary phase. This reversed-phase HPLC system can also be used to rapidly measure the amount of unreduced [99mTc]pertechnetate in preparations of hydrophylic anionic [99mTc]chelates that are used in clinical nuclear medicine (e.g. [99mTc]DTPA, and methylene diphosphonate).

Labeling of proteins with 105Rh

Abstract A complex of rhodium with the bifunctional chelating agent 4- p -toluic acid-diethylenetriamine has been prepared using 105 Rh as a tracer. This bifunctional chelate has been conjugated to human serum albumin and human IgG. Radiochemical conjugation yields are ∼30–40% and Rh IgG ratios as high as 2.5 are observed.

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.

Radiochemical purity evaluation of rhodium-105 complexes by magnesium oxide

We report here a new method for the radiochemical purity evaluation of 105Rh complexes using a magnesium oxide adsorption technique. The principle of the technique is based on the quantitative adsorption of uncomplexed rhodium by magnesium oxide powder, leaving the complexes in solution. Cysteine and 4-benzyldiethylenetriamine were complexed with 105Rh and the radiochemical purity of the resultant complexes was evaluated by thin layer chromatography and magnesium oxide adsorption. The advantage of magnesium oxide adsorption over thin layer chromatography is discussed.

Labeling of human serum albumin with 105Rhcysteine complexes

The conjugation of a complex formed by reacting RhCl3 with cysteine to human serum albumin has been investigated. Approximately 50% of the rhodium (labeled with 105Rh) was converted to the complex. Conjugation of the complex to HSA via the ECDI method resulted in yields of approximately 40% of the total rhodium or approximately 80% of the Rh-cysteine complex. No conjugation was observed in the absence of the ECDI. At approximately equal molar concentrations of rhodium and HSA, an average of approximately 0.4 rhodium atoms per HSA molecule was achieved.