Early chemotherapy response evaluation in tumors by 99mTc-DTPA-DG

Cancer Biother Radiopharm. 2008 Jun;23(3):363-70. doi: 10.1089/cbr.2007.0446.

Abstract

Purpose: The aim of this study was to evaluate the utility of 99mTc-diethylenetriaminepentaacetic acid-deoxyglucose (DTPA-DG) for monitoring the early response of tumors to chemotherapy.

Method: To evaluate the role of 99mTc-DTPA-DG in vitro chemotherapy, the uptake ratios assays were conducted using A549 lung cancer and MCF-7 breast cancer cells after the 2 tumor cell types had been treated with cisplatin and paclitaxel chemotherapeutic agents, respectively. Apoptosis in the 2 cell types, an indicator of chemotherapeutic action, was assessed by inverted fluorescence microscope and flow cytometry. The assessment of 99mTc-DTPA-DG in vivo was performed by scintigraphic imaging studies of 99mTc-DTPA-DG in MCF-7 mammary tumor cell xenografts at timed intervals after treatment. The animals were randomly assigned to 5 groups: group A, saline injection; group B, low-dose cisplatin; group C, high-dose cisplatin; group D, low-dose combination chemotherapy; and group E, high-dose combination chemotherapy. Imaging findings were correlated with the effectiveness of chemotherapy.

Results: The uptake rates of 99mTc-DTPA-DG by A549 lung cancer cells and MCF-7 breast cancer cells in the chemotherapeutic groups were all significantly lower than those in the controls (p < 0.01). The apoptotic ratios in the control groups were significantly lower than the apoptotic ratios in the chemotherapeutic treatment groups in the 2 tumor cell types. The uptake ratios and the apoptosis ratios are inverse correlation, which suggested that we could evaluate the chemotherapy response by the uptake of 99mTc-DTPA-DG in vitro. Scintigraphy in MCF-7 mammary tumor xenografts mice demonstrated that tumor could be clearly visualized by 99mTc-DTPA-DG. The efficacy of combined chemotherapy treatment in this xenograft model was assessed by scintigraphy of tumor/muscle ratios.

Conclusions: 99mTc-DTPA-DG is a targeted molecular imaging agent, promising in the evaluation of early response of tumors to chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Flow Cytometry
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy*
  • Mammary Neoplasms, Animal / diagnosis
  • Mammary Neoplasms, Animal / drug therapy*
  • Mice
  • Mice, Nude
  • Microscopy, Fluorescence
  • Neoplasm Transplantation
  • Radiopharmaceuticals* / pharmacology
  • Technetium Tc 99m Pentetate / analogs & derivatives*
  • Technetium Tc 99m Pentetate / pharmacology
  • Time Factors

Substances

  • Antineoplastic Agents
  • Radiopharmaceuticals
  • technetium 99m diethylenetriaminepentaacetate-deoxyglucose
  • Technetium Tc 99m Pentetate