Preclinical evaluation of [99m]Tc-labeled doxorubicin as a potential scintigraphic probe for tumor imaging

Cancer Biother Radiopharm. 2012 Apr;27(3):221-5. doi: 10.1089/cbr.2011.1086. Epub 2012 Mar 20.

Abstract

Background: The currently available radiopharmaceuticals are not specific for tumor imaging.

Purpose: The present study was conducted to radiolabel doxorubicin with Technetium-99m ([99m]Tc) as a scintigraphic marker of high DNA turnover/intercalation in malignant cells.

Methods: Labeling was done by direct method and the developed radiotracer was subjected to quality control tests. The blood kinetics, scintigraphy of tumor-bearing mice, and biodistribution were studied after intravenous injection of about 7.4 MBq of [99m]Tc-doxorubicin. The isotime (5 minutes) anterior images were acquired at different time intervals of 1.5, 3, and 4 hours.

Results: The labeling efficiency of [99m]Tc-doxorubicin was estimated to be more than 95%. The protein-binding efficiency was greater than 88% and in vitro stability was up to 24 hours. The biodistribution data support the clearance of the radioligand by dual (renal and hepatic) pathways. A semiquantitative data analysis of the anterior images indicated that a focal concentration of the radiotracer was seen in the tumor at 1.5 hours, which persisted in 3-hour and 4-hour images, respectively.

Conclusions: This scintigraphic approach, therefore, could be a powerful tool for cancer detection at early stage. The technique, however, needs further validation through animal experimentation and clinical studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / therapeutic use*
  • Carcinoma, Ehrlich Tumor / diagnostic imaging*
  • Carcinoma, Ehrlich Tumor / drug therapy*
  • Carcinoma, Ehrlich Tumor / pathology
  • Doxorubicin / therapeutic use*
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Organotechnetium Compounds*
  • Radionuclide Imaging
  • Radiopharmaceuticals*
  • Technetium*
  • Tissue Distribution
  • Tumor Cells, Cultured

Substances

  • Antibiotics, Antineoplastic
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Technetium
  • Doxorubicin