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

Zareneyrizi F., Yang D. J., Oh C., ILGAN S., Yu D., Tansey W., ...Daha Fazla

Anti-Cancer Drugs, cilt.10, sa.7, ss.685-692, 1999 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 10 Sayı: 7
  • Basım Tarihi: 1999
  • Doi Numarası: 10.1097/00001813-199908000-00009
  • Dergi Adı: Anti-Cancer Drugs
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.685-692
  • Anahtar Kelimeler: Antiangiogenesis, Colchicine, Tumor imaging, [99m)Tc]ethylene-dicysteine
  • Maltepe Üniversitesi Adresli: Hayır

Özet

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 ± 0.72 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.