Tc(V)-DMS tumor localization mechanism: a pH-sensitive Tc(V)-DMS-enhanced target/nontarget ratio by glucose-mediated acidosis.
Since the conception of the pentavalent technetium polynuclear complex of dimercaptosuccinic acid, Tc(V)-DMS, a great number of papers published on its clinical applicability forced us to question "how tumor tissue appropriates the Tc(V)-DMS." Preliminary in vitro studies with Ehrlich ascites tumor cells (EATC) indicated the pH-sensitive character of this tumor agent. From this finding and the well-established notion that malignant tumors are more acidic than normal tissue, the in vivo correlation of Tc(V)-DMS accumulation in tumor tissue with its tissue acidification was considered of interest. The systemic lowering of tumor tissue pH by the stimulation of aerobic glycolysis has been well reported. In the present paper, the response of Tc(V)-DMS tumor accumulation to acidification induced by the glucose administration was explored in EATC-bearing mice. Measurement of tumor tissue pH was carried out by direct microelectrode technique and by histochemical umbelliferone technique in tumor tissue excised from EATC bearing mice. The regional acidity distribution is correlated with the regional radioactivity distribution registered by autoradiography. Evidence related to the pH sensitiveness of Tc(V)-DMS in response to glycolytic acidification was gathered; the pH measurement and the in vivo biodistribution of the double-tracer macroautoradiography with C-14 deoxyglucose (C-14-DG) demonstrated that the regional tissue distribution of Tc(V)-DMS was superimposed to that of C-14-DG. The glucose interventional modality offers the premier foundation for the interpretation of Tc(V)-DMS accumulation in diagnostic studies of malignant tumors.
Horiuchi
K
K
Department of Patho-Functional Bioanalysis, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan. shkazuko@pharm.kyoto-u.ac.jp
Saji
H
H
Yokoyama
A
A
D000138:Acidosis / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D001786:Blood Glucose; D019275:Radiopharmaceuticals; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D005947:Glucose