pH sensitive properties of Tc(V)-DMS: analytical and in vitro cellular studies

• Published in: Nuclear medicine and biology 1998-10, Vol.25 (7), p.689-695
• Main Authors: Horiuchi, Kazuko, Saji, Hideo, Yokoyama, Akira
• Format: Article
• Language: English
• Subjects: Acetic Acid - chemistry; Acids - chemistry; Acids - metabolism; Animals; Biological and medical sciences; Biological Transport; Carcinoma, Ehrlich Tumor - chemistry; Carcinoma, Ehrlich Tumor - metabolism; Carcinoma, Ehrlich Tumor - pathology; Chromatography, Gel; Chromatography, Thin Layer; Contrast media. Radiopharmaceuticals; Electrophoresis, Cellulose Acetate - methods; Hydrogen-Ion Concentration; Ligand concentration; Ligands; Male; Medical sciences; Mice; Mice, Inbred Strains; Models, Chemical; Neoplasms, Experimental; Pentavalent technetium-99m dimercaptosuccinic acid; pH effect; pH-sensitive agent; Pharmacology. Drug treatments; Tc(V)-DMS; Technetium Tc 99m Dimercaptosuccinic Acid - chemistry; Technetium Tc 99m Dimercaptosuccinic Acid - metabolism; Time Factors
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/S0969-8051(98)00044-4

Numerous clinical studies with the pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS] seem to indicate its new role in nuclear oncology. Thus, we questioned what properties of the Tc(V)-DMS molecule associate with its tumoral tissue accumulation. Because studies have reported tumor tissue to be more acidic than normal tissue, acidification might be related to the Tc(V)-DMS localization in tumor tissue. Thus, in the present study, a working hypothesis drew to test the acidification as a plausible factor, and various analytical methods and an in vitro cellular system using Ehrlich ascites tumor cells (EATC) implemented. Analytical methodologies demonstrated the decrease of the overall negative charge of the Tc(V)-DMS molecule, promoted by the acidification of the analytical medium and the sample dilution. In the in vitrocellular experiment, acidification alone showed no effect on the radioactivity accumulation in EATC; nevertheless, if accompanied by a pre-dilution of the Tc(V)-DMS sample added into the cell incubation media, cellular radioactivity accumulation was observed. Thus, acidification as a mediator for the Tc(V)-DMS accumulation in tumoral cells, concurrently with dilution as the promoter of the process, constituted the foundation for discerning the working hypothesis.