title: Synthesis of [99mTc]ethylenedicysteine-colchicine for evaluation of antiangiogenic effect.
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.
authors.affiliation: Division of Diagnostic Imaging, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
authors.forename: F
authors.initials: F
authors.lastname: Zareneyrizi
authors.forename: D J
authors.initials: DJ
authors.lastname: Yang
authors.forename: C S
authors.initials: CS
authors.lastname: Oh
authors.forename: S
authors.initials: S
authors.lastname: Ilgan
authors.forename: D F
authors.initials: DF
authors.lastname: Yu
authors.forename: W
authors.initials: W
authors.lastname: Tansey
authors.forename: C W
authors.initials: CW
authors.lastname: Liu
authors.forename: E E
authors.initials: EE
authors.lastname: Kim
authors.forename: D A
authors.initials: DA
authors.lastname: Podoloff
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D003078:Colchicine / Q000493:pharmacokinetics; D003545:Cysteine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004355:Drug Stability; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging*; D011817:Rabbits; D011877:Radionuclide Imaging; D051381:Rats; D011916:Rats, Inbred F344; D013667:Technetium
chemical_list: D020533:Angiogenesis Inhibitors; C109063:ethylene dicysteine; D013667:Technetium; D003545:Cysteine; D003078:Colchicine