Synthesis and evaluation of a ^99mTc‐labeled tubulin‐binding agent for tumor imaging

Abstract

Cholchicine and its derivatives are very potent tubulin-binding compounds and can be used as a potential tumor targeting agents. In this study, colchicine was labeled with (99m) Tc via hydrazinonicotinic acid (HYNIC) and was investigated further. HYNIC/cholchicine was synthesized and labeling with (99m)Tc was performed at 95 °C for 15 min and radiochemical analysis included HPLC method. The stability of radiconjugate was checked in the presence of human serum at 37 °C up to 24 h. Biodistribution was studied in breast tumor-bearing mice. Labeling yield of 95.8 ± 0.54% was obtained corresponding to a specific activity of 54 MBq/µmol. Radioconjugate showed good stability in the presence of human serum. Biodistribution studies in tumor-bearing mice showed that (99m) Tc/HYNIC/colchicine conjugate accumulated in tumor with good uptake (3.17 ± 0.14% g/g at 1 h post-injection). The radioconjugate was cleared fast from normal organs and showed clearance through urinary and hepatobiliary systems with accumulation of activity in kidneys and intestine. This radioconjugate may be useful to assess the presence of tumor by imaging.

Size-Dependent Biodistribution of Fluorescent Furano-Allocolchicinoid-Chitosan Formulations in Mice

“…Our results on biodistribution demonstrated a decreased excretion of nano/micro sized formulation via hepatobiliary root, low accumulation in kidney and lungs, and increased retention in spleen. The same longer retention of colchicine conjugates in non-excretory organs was demonstrated earlier [ 8 , 34 ]. However, we found an increased quantity of AC-Chi and AC-NPs in spleen only.…”

“…However, we found an increased quantity of AC-Chi and AC-NPs in spleen only. In any case, longer retention in non-excretory organs can be translated into a better accumulation of such drugs in tumors, as has been shown by Korde et al [ 34 ], and Erfani et al [ 8 ]. In this work we have compared furano-allocolchicinoid preparations of three different sizes.…”

“…Colchicine biodistribution studies demonstrated its bioaccumulation in liver, intestine, kidney, and heart at organ/muscle ratios 11, 5, 7, and 6, respectively [ 8 ]. Unspecific tissue partition of colchicine may be reduced by decorating it with hydrophilic groups such as polyethylene glycol (PEG) [ 9 , 10 ].…”

99mTc‐labeled DTPA‐colchicine dimer with improved tumor uptake

“…Highly dynamic mitotic‐spindle microtubules are among the most successful targets for anticancer therapy . Colchicine was therefore selected as the biomolecule for preparing tumor‐targeted radiopharmaceuticals for imaging or therapy purpose …”

“…9 Colchicine was therefore selected as the biomolecule for preparing tumor-targeted radiopharmaceuticals for imaging or therapy purpose. [10][11][12][13][14][15][16][17][18][19][20][21][22] Derivatization of CHC to the suitable precursor was necessary for subsequent 99m Tc-labeling. Diethylene triamine pentaacetic acid (DTPA) is an aminopolycarboxylic acid consisting of a diethylenetriamine backbone with 5 carboxymethyl groups.…”