Biodistribution and scintigraphy of [111In]DTPA-adriamycin in mammary tumor-bearing rats

Anticancer Drugs. 1999 Jan;10(1):89-95. doi: 10.1097/00001813-199901000-00011.

Abstract

The aim of this study was to develop an 111In-labeled diethylenetriamine pentaacetic acid-adriamycin (DTPA-ADR) conjugate to image breast cancer. DTPA-ADR was synthesized by reacting adriamycin with DTPA anhydride in the presence of carbonyldiimidazole. After dialysis (MW cut off was 500), the product was freeze-dried (yield 40-50%). An in vitro cell culture study was performed using cells from the 13,762 Fischer rat mammary tumor line. Drug concentrations tested were 0.1-100 microM. Biodistribution studies were conducted at 0.5, 2, 24 and 48 h in mammary tumor-bearing rats (n = 3/time interval, 10 microCi/rat, i.v.) with 13,762 cells (10(5) cells/rat, s.c.). Planar imaging and autoradiograms were obtained at the same intervals. In vitro cell culture assays showed an IC50 of 0.1 +/- 0.01 microM for ADR and 7.2 +/- 0.29 microM for DTPA-ADR, respectively. In biodistribution studies, tumor/blood uptake ratios of [111In]DTPA-ADR at 0.5, 2, 24 and 48 h were 0.55 +/- 0.17, 0.94 +/- 0.17, 3.06 +/- 0.53 and 3.66 +/- 0.35, respectively, whereas those for [111In]DTPA (control) were 1.19 +/- 0.69, 0.84 +/- 0.07, 0.56 +/- 0.10 and 0.60 +/- 0.03, respectively. The tumor uptake value (%ID/g) of [111In]DTPA-ADR at 0.5 h was 0.20 +/- 0.06. Planar images and autoradiograms showed good visability of tumors. Biodistribution, autoradiography and radionuclide imaging of [111In]DTPA-ADR in breast tumor-bearing rats showed that tumor-to-blood ratios increased steadily between 30 min and 48 h. These results indicate that DTPA-ADR, a new cancer imaging agent, might be useful in the diagnosis of breast cancer and may predict a therapeutic effect prior to treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacokinetics*
  • Autoradiography
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacokinetics*
  • Female
  • Indium Radioisotopes*
  • Inhibitory Concentration 50
  • Mammary Neoplasms, Experimental / diagnostic imaging*
  • Mammary Neoplasms, Experimental / metabolism*
  • Pentetic Acid / analogs & derivatives*
  • Pentetic Acid / pharmacokinetics*
  • Radionuclide Imaging / methods
  • Rats
  • Rats, Inbred F344
  • Tissue Distribution
  • Tumor Cells, Cultured / metabolism

Substances

  • Antineoplastic Agents
  • Indium Radioisotopes
  • indium DTPA-adriamycin
  • Pentetic Acid
  • Doxorubicin