Le challenge majeur des chimistes specialises dans les radiopharmaceutiques est de synthetiser des molecules marquees stables, specifiques d'un organe ou d'une fonction, qui se fixent avec un grand pourcentagesur leur cible et qui sont ensuite rapidement eliminees. La connaissance de la chimie est indispensable pour marquer une molecule sans la denaturer. Deux strategies sont appliquees, que ce soit pour un marquage a l'iode ou au technetium, la fixation directe sur une molecule modifiee qui reagit avec l'isotope et l'approche indirecte par l'intermediaire d'un synthon bifonctionnel. Aujourd'hui de nouveaux ligands bifonctionnels sont mis au point pour permettre un marquage simple, stable et rapide de biomolecules : DTPA, HYNIC, MAG3, carbonyl pour le technetium, tyrosine ou reactif de Bolton-Hunter pour l'iode. Leurs inconvenients majeurs par rapport a un marquage direct restent que la majorite ne sont pas commercialises et doivent donc etre synthetises et qu 'une etape supplementaire de purification est necessaire.

UNLABELLED:99mTcN-NOET (bis[N-ethoxy,N-ethyl]dithiocarbamato nitrido technetium (V)) has been proposed for myocardial perfusion imaging. Biodistribution, safety, and dosimetry were studied in 10 healthy volunteers (5 at rest and 5 during exercise). METHODS:Biodistribution was studied by acquiring dynamic images up to 60 min after injection and whole-body images up to 24 h after injection. The MIRDOSE3 analysis program was used for radiation dosimetry calculations. RESULTS:Safety parameters measured to 48 h after injection revealed no clinically significant changes. Cardiac uptake of 99mTcN-NOET was high (2.9%-3%), with biologic half-life of 210-257 min on average. Lung uptake of 99mTcN-NOET was higher (10%-20%) but, on average, biologic half-life was shorter (1-77 min). Clearance from the blood was rapid (5% by 5 min). Radiation dosimetry calculations indicated an effective absorbed dose of 5.11 x 10(-3) mSv/MBq at rest and 5.38 x 10(-3) mSv/MBq after exercise. CONCLUSION:99mTcN-NOET exhibits high cardiac uptake and an estimated effective absorbed dose comparable with that of the other 99mTc-labeled compounds used in myocardial perfusion imaging.

The new diisocyanide ligand L possessing a polyether backbone was synthesized and its complexing ability towards metal such as 99mTc, Cu and Re was evaluated. Using the γ-emitting 99mTc isotope (at the non-carrier added level), L led to the formation of a cationic species whose biodistribution in Swiss mice revealed a moderate but lasting heart uptake. No redox properties of the ligand were observed by complexation since reaction with a CuII salt led to the formation of a CuII complex, characterized by EPR, IR and elemental analysis. Rhenium complexation gave two new chelates [ReIIICl3PPh3L] and [ReI3]BPh4, identified by IR NMR, elemental analysis and conductimetric studies. The usefulness of rhenium chemistry to approach 99mTc properties is discussed.

Thirty patients with recent myocardial infarction were intravenously injected with the modified fatty acid [123I]16-iodo-3R,S-methyl hexadecanoic acid (MIHA) at peak exercise to quantify viable myocardium after infarction. The results were analysed visually and quantitatively and compared with those obtained after injection of thallium 201 at peak exercise with single-photon emission computed tomography (SPECT) imaging immediately and 4 hours later. Ventriculography was used to study regional wall motion in all patients. In the visual comparison of 201Tl- and MIHA-SPECT scintigrams, 98.8% of normal segments (N) and 96% of temporary thallium-defect segments (T) were N or T on MIHA-SPECT scintigrams (91.3% and 70.5%, respectively, in the quantitative analyses). In contrast, 47.2% of permanent thallium-defect segments (P) were N or T on the MIHA-SPECT scintigrams (20.6% in the quantitative analysis). Revascularization therapy could only be recommended on the basis of MIHA-SPECTs in 5 to 8 of the 30 patients. To confirm the superiority of MIHA over 201Tl to evaluate myocardial viability, one must compare their uptake with myocardial contractility after revascularization.