Satoshi G. Harada MD, PhD, Presenter: Nothing to Disclose

Shigeru Ehara MD, Abstract Co-Author: Nothing to Disclose

Keizo Ishii PhD, Abstract Co-Author: Nothing to Disclose

Koichiro Sera, Abstract Co-Author: Nothing to Disclose

Takahiro Satoh DSc, Abstract Co-Author: Nothing to Disclose

Jun Ito DSc, Abstract Co-Author: Nothing to Disclose

We developed fluoroscopically detectable liquid-core microcapsules with a high affinity for radiation-induced P-selectin that release highly oxygenated liquid on irradiation. By treating Meth A fibrosarcoma in BALB/c mice under normal breathing with 3 radiotherapy sessions, we tested the microcapsules’ ability to radiosensitize cells via the oxygen effect.

The microcapsules were prepared by spraying a mixture of 3% hyaluronic acid and 2% alginate, supplemented with 2200 ppm O2, on 0.5 mol/l FeCl2 containing 0.1 μmol/l P-selectin glycoprotein ligand-1 and FcSv antibody to P-selectin. To induce P-selectin, the tumor was radiated with 5 or 10 Gy 60Co γ-rays. Next, 100 milion microcapsules were injected i.v. 1 h before the P-selectin level peaked and were allowed to interact with P-selectin for 1–6 h postradiation. The 2nd and 3rd sessions were conducted at a 6-h interval, identical to the 1st session. P-selectin was detected by in situ hybridization and western blotting. O2 content was monitored using an O2 electrode.

The microcapsules were 20.3 ± 3.8 μmΦ, with a 19.7 ±  1.2 μmΦ liquid core. The 1st session proximally induced P-selectin, which peaked 6 h postradiation; P-selectin was expressed in 78.1% ±  6.7% and 93.4% ±  7.8% endothelial cells after 5 Gy and 10 Gy radiations, respectively. The microcapsules were injected 5 h after the 1st session and could be traced fluoroscopically. Maximum accumulations were observed 6.2 ± 1.7 h postinjection, as in the microscopic study. After the 2nd session, the accumulated microcapsules released the oxygenated liquid and gelatinized their outer shell. The released liquid increased the tumor O2, thus increasing the 2nd session’s effect. The O2 content increased continually due to the gradual release of the oxygenated liquid from the shell, thus enhancing the 3rd session’s effect. These phenomena increased the antitumor effect of radiation (OER 1.8).

Our microcapsules may lead to the discovery of a novel radiosensitizing technique utilizing the oxygen effect.

Innovated microcapsules increase the clinical applicability of radiosensitization via oxygen effect.

Harada, S, Ehara, S, Ishii, K, Sera, K, Satoh, T, Ito, J, Radiosensitization via Oxygen Effect by Using Microcapsules with a Highly Oxygenated Liquid Core That Is Released on Irradiation.  Radiological Society of North America 2008 Scientific Assembly and Annual Meeting, February 18 - February 20, 2008 ,Chicago IL. http://archive.rsna.org/2008/6008141.html