Synthesis of [99mTc]ethylenedicysteine-colchicine for evaluation of antiangiogenic effect

Anticancer Drugs. 1999 Aug;10(7):685-92. doi: 10.1097/00001813-199908000-00009.

Abstract

Angiogenesis is in part responsible for tumor growth and the development of metastasis. Radiolabeled angiongenesis inhibitors would be useful to assess tumor microvasculature density. Colchicine (COL), a potent antiangiogenic agent, is known to inhibit microtubule polymerization and cell arrest at metaphase. This study aimed to develop 99mTc-labeled COL (EC-COL) using ethylenedicysteine (EC) as a chelator to assess tumor microvascular density. EC was conjugated to trimethylcolchicinic acid using N-hydroxysuccinimide and 1-ethyl-3-dimethylaminopropyl carbodiimide as coupling agents with a yield of 50-60%. In vivo stability was analyzed in rabbit serum at 0.5-4 h. Tissue distribution and planar imaging studies of [99mTc]EC-COL were evaluated in breast tumor-bearing rats at 0.5, 2 and 4 h. The data was compared to that using [99mTc]EC (control). The radiochemical yield of [99mTc]EC-COL was greater than 95%. [99mTc]EC-COL was stable in rabbit serum. In vivo biodistribution of [99mTc]EC-COL in breast tumor-bearing rats showed increased tumor-to-blood (0.52+/-0.12 to 0.72+/-0.07) and tumor-to-muscle (3.47+/-0.40 to 7.97+/-0.93) ratios as a function of time. Conversely, tumor-to-blood values showed a time-dependent decrease with [99mTc]EC over the same time period. Planar images confirmed that the tumors could be visualized clearly with [99mTc]EC-COL from 0.5 to 4 h. [99mTc]EC-COL may be useful to assess antiangiogenic and therapeutic effects during chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors* / pharmacology
  • Animals
  • Colchicine* / pharmacokinetics
  • Cysteine / analogs & derivatives*
  • Cysteine / pharmacokinetics
  • Drug Stability
  • Female
  • Mammary Neoplasms, Experimental / diagnostic imaging*
  • Rabbits
  • Radionuclide Imaging
  • Rats
  • Rats, Inbred F344
  • Technetium*

Substances

  • Angiogenesis Inhibitors
  • ethylene dicysteine
  • Technetium
  • Cysteine
  • Colchicine