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

Abstract

1. 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.

2. For the metabolism analysis, a 2 mg (2.98 MBq)/kg of [glucose-U-¹⁴C]-SQAP (CP-3839) was intravenously injected. The injected SQAP was decomposed into a stearic acid and a sulfoquinovosylpropanediol (SQP) in the body.

3. The degradation was relatively slow in the carcinoma tissue.1,3-propanediol[1-¹⁴C]-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.

4. 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.

5. 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.

Keywords:

• Sulfoquinovosylacylpropanediol (SQAP)
• 14C-SQAP
• radiosensitizer
• KSN-nude mice
• ADME
• human pulmonary carcinoma
• tumor xenograft
• whole-body autoradiography

Disclosure statement

There are no potential conflicts of interest related to this work to disclose.

Additional information

Funding

This work was supported by the Program for Promotion of Fundamental Studies in Health Science of the National Institute of Biomedical Innovation (NiBio), Japan.