Technetium‐99m radiochemistry for pharmaceutical applications

Abstract

Technetium-99m ( Tc) is a widely used radionuclide, and the development of Tc imaging agents continues to be in demand. This overview discusses basic principles of Tc radiopharmaceutical preparation and design and focuses on the Tc radiochemistry relevant to its pharmaceutical applications. The Tc complexes are described based on the most typical examples in each category, keeping up with the state-of-the-art in the field. In addition, the main current strategies to develop targeted Tc radiopharmaceuticals are summarized.

PIDAZTA: Structurally Constrained Chelators for the Efficient Formation of Stable Gallium‐68 Complexes at Physiological pH

“…Furthermore, rapid complex formation at ambient temperature and physiological pH is an attractive feature, being indispensable for labeling of targeting vectors that do not tolerate elevated temperatures or challenging pH values. Those are, for example, large proteins such as antibodies, which is, however, of lesser relevance for the short‐lived 68 Ga. More importantly, such properties would provide access to 68 Ga tracers through “shake‐and‐shoot” kits that is, by simple addition of 68 Ge/ 68 Ga generator eluate to preconditioned vials containing lyophilized precursor and excipients, as known from 99m Tc radiopharmaceuticals …”

“…Those are, for example, large proteins such as antibodies, which is, however,o fl esser relevance for the short-lived 68 Ga. More importantly,s uch properties would provide access to 68 Ga tracers through "shake-and-shoot" kits that is, by simple addition of 68 Ge/ 68 Ga generator eluate to preconditioned vials containing lyophilized precursor and excipients, as known from 99m Tc radiopharmaceuticals. [37] However,t he cyclic polyaza-polycarboxylate chelators DOTA and NOTA, whicha re most frequently used in 68 Ga tracers, do not allow forl abeling at neutral pH, single-digit mm concentration, and room temperature within af ew minutes.H owever, this was found to be feasible for severala cyclics tructures at slightly acidic pH [38] as well as for phosphinate-pendant triazacyclononanes at pH 3. [39,40] Against this background, it is remarkable that the optimal pH for labeling of PIDAZTAi somers L1/L2 lies between 7and 8, whereas at pH 7.5, nearly quantitative labeling (89.2 and 93.5 %f or L1 and L2,r espectively)a t room temperature is achieveda lready at chelator concentrations below 10 mm ( Figure 6).…”

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“…Various ligands have been labeled with 99m Tc by direct method using stannous chloride as the reducing agent. 99m Tc-DTPA (Diethylenetriamine pentaacetic acid) and 99m Tc-MDP (Methylene diphosphonate) are some of the radiopharmaceuticals clinically used to diagnose the disease in nuclear medicine practices 3,4 . Additionally, some carbohydrates like glucoheptonate and glucuronic acid are carboxylic acid analogs of glucose, which have been coordinated with 99m Tc.…”

99Mo recoil atoms yield in the 100Mo(p,x) reaction on cyclotron irradiation of Mo nanofilms

“…Technetium‐99m is a crucial component of many medical imaging tests covering almost every organ of the human body. Technetium‐99m–labeled compounds are employed in more than 80% of all of the diagnostic procedures in nuclear medicine. Presently, 95% of 99 Mo in the world is produced by neutron‐induced reactions on HEU 235 U (enrichment > 80%) targets.…”