Karen Libson

The chemistry of rhenium and technetium as related to the use of isotopes of these elements in therapeutic and diagnostic nuclear medicine.

The beta emitting isotopes 186Re and 188Re are logical choices on which to base therapeutic radiopharmaceuticals that might be expected to be analogous to diagnostic radiopharmaceuticals based on 99mTc. However, the chemistry of rhenium is sufficiently different from that of technetium so that the development of Re radiopharmaceuticals often cannot be predicated on the known chemistry and biological behavior of 99mTc radiopharmaceuticals. The relevant chemical differences involve the greater stability of the higher oxidation states of Re (and thus the greater tendency of reduced Re radiopharmaceuticals to undergo re-oxidation to perrhenate), and the greater substitution inertness of reduced Re complexes. These differences are illustrated in the preparation and use of 186Re (Sn)-HEDP and 99mTc(Sn)-HEDP diphosphonate radiopharmaceuticals designed, respectively, for palliative therapy and diagnosis of metastatic cancer to bone, and in the preparation and biodistribution of tr[186Re(DMPE)2Cl2]+ and [186Re(DMPE)3]+, analogs to the potential myocardial perfusion imaging agents tr-[99mTc(DMPE)2Cl2]+ and [99mTc(DMPE)3]+. [HEDP = (1-hydroxyethylidene)diphosphonate; DMPE = 1,2-bis(dimethylphosphino)ethane].

Recent Advances in Technetium Chemistry: Bridging Inorganic Chemistry and Nuclear Medicine

Abstract Recent research that bridges the apparently disparate disciplines of inorganic chemistry and nuclear medicine is described.

Myocardial perfusion imaging with 99mTc-DMPE in man

Technetium-99m DMPE (99mTc-DMPE) is a newly synthesized myocardial perfusion imaging agent that shows intense myocardial accumulation in the dog. In the present study, dosimetry and potential clinical usefulness of this agent were assessed in four human subjects. Absorbed radiation doses were low, with the highest doses consisting of 200 mrad/mCi (54 μGy/MBq) to the gallbladder and 160 mrad/mCi (43 μGy/MBq) to the liver. No evidence of clinical toxicity was found. Technetium-99m DMPE did image the myocardium, but the ratio of target to nontarget activity was less favorable than that observed in the dog. Intense hepatic 99mTc-DMPE activity interfered with clinical imaging of the cardiac apex in two of the four subjects. We conclude that the prototype radiopharmaceutical, 99mTc-DMPE, is capable of myocardial perfusion imaging in man but the planar myocardial images produced are of inferior quality compared with 201Tl myocardial images. Further work is justified to develop related compounds to overcome the clinical limitations described.

The biological distributions of some technetium-MDP components isolated by anion exchange high performance liquid chromatography.

Individual components of 99mTc(NaBH4)-MDP mixtures, separated by anion exchange HPLC, have been evaluated as skeletal imaging agents in rats. Biodistribution data show that the evaluated components exhibit markedly different bone uptakes and soft tissue localizations. The component with the highest bone uptake and the highest bone/muscle and bone/blood ratios, is the major component of carrier-added 99mTc(NaBH4)-MDP formulations prepared at pH 8.2. Comparative scintiphotos illustrate the enhanced imaging performance of this component vs unseparated reaction mixtures.

Myocardial scintigraphy with 99mTc-tris-DMPE in man

Cardiac scintigraphy was performed in six patients with a documented previous myocardial infarction, in one patient with mitral regurgitation, and in four healthy volunteers following administration of 99mTc-tris-DMPE. An intense early blood pool phase permitted gated blood pool scintigraphy and left ventricular ejection fraction calculation. A myocardial phase 12–14 h later permitted myocardial perfusion imaging. The rest myocardial perfusion image quality with 99mTc-tris-DMPE appeared to be superior to the resting image quality obtained with 99mTc-dichloro-DMPE but was inferior to the resting image quality obtained with 201Tl.

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

A series of eight neutral technetium(II)-99m complexes of general formula tr-[99mTcIID2X2]0, where D represents a chelating ditertary phosphine or arsine ligand and X represents a halide or pseudohalide ligand, has been prepared and characterized by HPLC comparisons to the known 99Tc analogs. Several members of this series exhibit significant brain uptake in rats, with maximum uptake (1.2% dose/brain at 1 min after injection) being exhibited by tr-[99mTcII (DIARS)2Cl2]0 where DIARS represents o-phenylenebis(dimethylarsine). Surprisingly, several cationic Tc(III) analogs, tr-[99mTcD2X2]+, also exhibit significant brain uptake, presumably via a mechanism which involves in vivo reduction to the neutral Tc(II) form. The complicated interrelationships among the chemical and biological properties of the tr-[99mTcIII/IID2X2]+/0 couples, and the dependencies of these properties on the nature of D and X, provide possible means by which this class of complexes might be manipulated to yield an effective 99mTc brain perfusion imaging agent.

HPLC separated fractions of 99mTc(NaBH4)-HEDP as myocardial infarct imaging agents

Component fractions of 99mTc(NaBH4)-HEDP mixtures, isolated by anion exchange high performance liquid chromatography (HPLC), have been evaluated as myocardial infarct imaging agents in two animal models. Results from both the isoproterenol-induced myocardial infarction model, and the heat-induced myocardial necrosis model, show that the several HPLC isolated components exhibit significantly different abnormal/normal heart uptake ratios. In addition, the HPLC isolated component of shortest chromatographic retention time exhibits a higher abnormal/normal heart uptake ratio than does 99mTc(Sn)-PyP, the current agent of choice for clinical myocardial infarct imaging.