Distribution and metabolism of 14C-sulfoquinovosylacylpropanediol (14C-SQAP) after a single intravenous administration in tumor-bearing mice. (4th March 2019)

• Record Type: Journal Article
• Authors: Ruike, Tatsushi; Kanai, Yoshihiro; Iwabata, Kazuki; Matsumoto, Yuki; Murata, Hiroshi; Ishima, Masahiro; Ohta, Keisuke; Oshige, Masahiko; Katsura, Shinji; Kuramochi, Koji; Kamisuki, Shinji; Sahara, Hiroeki; Miura, Masahiko; Sugawara, Fumio; Sakaguchi, Kengo
• Is Part Of: Xenobiotica. Volume 49:Number 3(2019:Mar.)
• Page Start: 346
• Page End: 362
• Publication Date: 2019-03-04
• Subjects: Sulfoquinovosylacylpropanediol (SQAP) -- 14C-SQAP -- radiosensitizer -- KSN-nude mice -- ADME -- human pulmonary carcinoma -- tumor xenograft -- whole-body autoradiography; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2018.1448949
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: Sulfoquinovosylacylpropanediol (SQAP) is a novel potent radiosensitizer that inhibits angiogenesis in vivo and results in increased oxigenation and reduced tumor volume. We investigated the distribution, metabolism, and excretion of SQAP in male KSN-nude mice transplanted with a human pulmonary carcinoma, Lu65. For the metabolism analysis, a 2 mg (2.98 MBq)/kg of [glucose-U- 14 C]-SQAP (CP-3839) was intravenously injected. The injected SQAP was decomposed into a stearic acid and a sulfoquinovosylpropanediol (SQP) in the body. The degradation was relatively slow in the carcinoma tissue.1, 3-propanediol[1- 14 C]-SQAP (CP-3635) was administered through intravenous injection of a 1 mg (3.48 MBq)/kg dose followed by whole body autoradiography of the mice. The autoradiography analysis demonstrated that SQAP rapidly distributed throughout the whole body and then quickly decreased within 4 hours except the tumor and excretion organs such as liver, kidney. Retention of SQAP was longer in tumor parts than in other tissues, as indicated by higher levels of radioactivity at 4 hours. The radioactivity around the tumor had also completely disappeared within 72 hours.