Related Experiment Videos
Tc(V)-DMS tumor localization mechanism: a pH-sensitive Tc(V)-DMS-enhanced target/nontarget ratio by glucose-mediated
K Horiuchi1, H Saji, A Yokoyama
1Department of Patho-Functional Bioanalysis, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan. shkazuko@pharm.kyoto-u.ac.jp
Abstract:
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.
Insights
Technetium (V) dimercaptosuccinic acid (Tc(V)-DMS) accumulation in tumors is pH-dependent. Glucose administration acidifies tumors, enhancing Tc(V)-DMS uptake, which is crucial for interpreting its diagnostic use in cancer.
Area of Science:
- Biomedical imaging
- Radiochemistry
- Oncology
Background:
- Pentavalent technetium polynuclear complex of dimercaptosuccinic acid (Tc(V)-DMS) is a potential tumor imaging agent.
- Malignant tumors exhibit lower pH than normal tissues due to aerobic glycolysis.
- The pH-sensitive nature of Tc(V)-DMS suggests a correlation between tumor acidity and its accumulation.
Purpose of the Study:
- To investigate the in vivo correlation between Tc(V)-DMS accumulation in tumor tissue and tumor acidification.
- To explore the response of Tc(V)-DMS tumor accumulation to glucose-induced acidification in Ehrlich ascites tumor cell (EATC)-bearing mice.
Main Methods:
- Tumor tissue pH was measured using microelectrode and histochemical umbelliferone techniques.
- Regional radioactivity distribution was assessed by autoradiography.
- In vivo biodistribution was evaluated using dual-tracer macroautoradiography with C-14 deoxyglucose (C-14-DG).
Main Results:
- Tc(V)-DMS tumor accumulation was found to be pH-sensitive and correlated with tumor acidity.
- Glucose administration induced tumor acidification, leading to increased Tc(V)-DMS uptake.
- The regional distribution of Tc(V)-DMS overlapped with that of C-14-DG, indicating similar uptake patterns.
Conclusions:
- The study provides evidence for the pH sensitivity of Tc(V)-DMS in response to glycolytic acidification.
- Glucose administration can be used to enhance Tc(V)-DMS accumulation in tumors.
- This understanding is fundamental for interpreting Tc(V)-DMS biodistribution in cancer diagnostic studies.