In vivo biological evaluation of ¹³¹I radiolabeled-paclitaxel glucuronide (¹³¹I-PAC-G)

Abstract

Paclitaxel (PAC) is a natural occurring diterpene alkoloid originally isolated from the bark of Taxus Brevifolia. It is one of the most important antitumor agents for clinical treatment of ovarian, breast non-small cell lung and prostate cancers. It is known that these types of cancer cells have high β-glucuronidase enzyme which can catalyze the hydrolysis of glucuronides. This is why the synthesis compounds which undergo glucuronidation come into question in the imaging and therapy of these cancer cells. The aim of current study is conjugation of glucuronic acid (G) to the starting substance PAC, labeling with 131I and to perform its in vivo biological evaluation. Glucuronic acid derived paclitaxel compound [paclitaxel-glucuronide (PAC-G)] was labeled with 131I using iodogen method. According to thin layer radio chromatography (TLRC) method, the radiochemical yield of 131I-PAC-G was 84.30 ± 7.40% (n=10). The biodistribution of 131I-PAC-G in healthy female and male Wistar Albino rats has been investigated. Imaging studies on male Balb-C mice were performed by using the Kodak FX PRO in vivo Imaging System. The range of the breast/blood, breast/muscle; ovary/blood, ovary/muscle ratios is approximately between 1.29 and 11.34 in 240 min, and between 0.71 and 8.24 in 240 min for female rats. The prostate/blood and prostate/muscle ratio is between 1.94 and 6.95 in 30 min for male rats. All these experimental studies indicate that 131I-PAC-G may potentially be used in breast, ovary and prostate tissues as an imaging agent. Also it is thought that 131I-PAC-G bears a theraphy potential because of the 131I radionuclide and can be improved with further investigations.

Synthesis of radioiodinated thymoquinone glucuronide conjugated magnetic nanoparticle (¹²⁵i-tqg-fe₃o₄) and its cytotoxicity and in vitro affinity

“…Labeling glucuronide derivatives with technetium-99m ( 99m Tc) or radioiodine with the advantage of higher expression of beta glucuronidase enzymes in tumor tissues rather than normal tissues, have been studied by our group for more than a decade 1,2,4,5,[8][9][10][11]13,15,16,21,[23][24][25][26][27]29,30 .…”

Improving external beam radiotherapy by combination with internal irradiation

“…However, these cannot be translated to treatment of other entities. Besides, radioactive-labelled cytostatic drugs and hormone derivatives, 4 particularly monoclonal antibodies (mAb) have been radiolabelled and investigated. 5 Given a substantial difference in the target receptor expression between the tumour cells and surrounding normal tissues, a dose fall-off between both tissues can be expected.…”