Experimental and Clinical Therapeutics

Monday, October 17, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP128) Quantitative dosimetry and biodistribution of radionuclide concentrator therapy in ad-NIS transduced head and neck carcinoma.

Krager, Kimberly*,1, Niu, Gang1, Madsen, Mark2, Graham, Michael2, Stevenson, Gail3, Liu, Zhonglin3, Barrett, Harrison3, Domann, Frederick 1, 1 Radiation Oncology, Iowa City, IA, United States2 Department of Radiology, Iowa City, IA, United States3 Department of Radiology, Tucson, AZ, United States

ABSTRACT- Survival rates for patients with head and neck squamous cell carcinoma (HNSCC) have not improved in the past 30 years, thus new treatment options targeting HNSCC are clearly needed. Thyroid cancer therapy can provide insight into improving survival rates for HNSCC patients. Well-differentiated thyroid tumors can be easily imaged and treated based on their high level expression of the sodium iodide symporter (NIS). Similarly, adenoviral NIS-transduced HNSCC cells are able to accumulate radioiodine. In order to non-invasively measure, in real time, systemic radiation distribution in animals bearing tumors that received Ad-NIS and a radiotracer we used microSPECT. Xenografted tumors arising from the human SCC cell line FaDu were intratumorally injected with 1 x 109 particles of Ad-NIS or Ad-Bgl II; forty-eight hours later the mice were given 5 mCi of 99mTcO4- via tail vein injection and dynamically imaged by microSPECT. In another experiment to determine therapeutic radiation dose delivery, FaDu xenografts were injected with Ad-NIS intratumorally on three consecutive days. On day five, 1 mCi of 131I was administered, and the mice were imaged over a time course using a pinhole collimator fitted to a gamma camera. The doses delivered to the tumors were calculated based on the counts received from the region of interest and the volume of the tumor and ranged from 2.5-9.7 Gy. The radioactivity in the tumors was retained at levels above background for at least 24 hours following 131I administration. Time-activity curves determined from the microSPECT dynamic images showed that Ad-NIS injected tumors accumulated and retained more radioactivity than control tumors. Moreover, retention times in vivo were considerably longer than previously observed in vitro. In addition, individual time-activity curves were markedly variable, thus emphasizing the heterogeneity of adenoviral gene delivery and iodide uptake in the different Ad-NIS treated tumors. The ability to measure NIS activity with functional imaging suggests that it may become possible to more accurately predict the response to Ad-NIS gene-radioiodine therapy based on a simple image analysis following gene transfer.

Key words: sodium iodide symporter, head and neck squamous cell carcinoma

Internet Services provided by
Allen Press, Inc. | 810 E. 10th St. | Lawrence, Kansas 66044 USA
e-mail assystant-helpdesk@allenpress.com | Web www.allenpress.com
2005 RRS