2660 Detection of Serum Interleukin-10 Levels In Nasopharyngeal Carcinoma

X. Li, G. Xu, Y. Chen, D. Wu, M. Yan, D. Yang

Department of Radiation Oncology, The Second Clinical Medicine College, Jinan University (Shenzhen People’s Hospital),Shenzhen, China

Purpose/Objective(s): To evaluate the clinical significance of detecting of interleukin(IL)-10 serum levels in nasopharyngealcarcinoma patients.

Materials/Methods: IL-10 serum levels were detected by ELISA in 60 patients with nasopharyngeal carcinoma and 20 casesof normal control subject, and the dynamic variations in IL-10 serum levels between pre-radiotherapy and post-radiotherapywere evaluated in part of patients.

Results: IL-10 serum levels in patients with nasopharyngeal carcinoma were significantly higher than that in normal controlsubject (p�0.005). IL-10 serum levels in stageIand II patients were significantly lower than that in stage III and IVpatients(p�0.05). IL-10 serum levels in patients with lymph node metastases or distant metastases were higher than that inpatients without lymph node metastases or distant metastases, but no statistically significance were observed. IL-10 serum levelsin all but 2 post-radiotherapy patients significantly decreased as compared to that of pre-radiotherapy (p�0.005), these 2patients had local recurrence.

Conclusions: Detection of IL-10 serum levels is of significance in diagnosing, staging, and evaluating the outcome fornasopharyngeal carcinoma patients, and it is worthy of further studies.

Author Disclosure: X. Li, None; G. Xu, None; Y. Chen, None; D. Wu, None; M. Yan, None; D. Yang, None.

2661 Induction of Graft-Versus-Host Disease by Low Dose Rates of Total Body Irradiation in ExperimentalModels

S. Schwarte1, F. Bruns1, J. Fruehauf1, Y. Sorge2, S. Skubich2, M. W. Hoffmann2

1Dept. of Radiation Oncology, Medical School Hannover, Hannover, Germany, 2Dept. of Visceral- and TransplantationSurgery, Medical School Hannover, Hannover, Germany

Background: Allogeneic bone marrow transplantation (BMT) is a curative treatment for leukemias. For several reasons,conditioning regimens include total body irradiation (TBI) as a key part prior to BMT. Graft-versus-Host-Disease (GvHD) isa serious side-effect of BMT, whereas a mild GvHD is correlated with a relapse reducing Graft-versus-Leukemia- (GvL-) effect.

Purpose/Objective(s): It was the aim of the present study to examine radiobiological effects of different radiation parameters,in particular dose rate, on incidence of acute GvHD in a transgeneic mouse model.

Materials/Methods: Different radiation devices and dose rates (in brackets) were used: a 60Cobalt source (0.85 Gy/min), a137Cesium source (2.5 Gy/min) and a 6-MV linear accelerator (0.85, 1.5, 2.5 and 5 Gy/min). Additionally, different total doseswere used for total body irradiation (TBI) of the mice. 24 hours after TBI allogeneic bone marrow cells (BMC) and lymph nodecells (LNC) were injected intravenously. After BMT, the recipients were observed for 120 days for clinical signs of GvHD andsamples of liver, skin and terminal ileum were taken for histologic examinations and flow cytometry analyses were performedas well.

Results: GvHD was induced by a dose rate of 0.85 Gy / min (60Cobalt source), a total dose of 9 Gy and 5 x 10(5) LNC plus5 x 10(6) BMC. All recipients died within 30 days. TBI with dose rates higher than 1.5 Gy/min by linear accelerators did notlead to consistent inductions of acute lethal GvHD. Only a dose rate of 0.85 or 1.5 Gy/min by a total single dose of 9 Gy with6-MV-photons led to similar results. With the cesium source, a lethal GvHD could not be induced, but vigorous skin lesionsdid occur in recipients. Histologic examinations of liver, skin and terminal ileum showed 50 days after BMT typical signs ofGvHD. Flow cytometry-studies showed proliferation at day 1 and 4 and activation of T cells at day 50 after BMT.

Conclusions: Although correlation of total dose of conditioning and incidence of acute GvHD has been described, the influenceof dose rate on GvHD induction has been unknown so far. Our data show dose rates in murine models must be equal or lessthan 1.5 Gy / min to induce a lethal acute GvHD reproducibly. Different immunological processes after radiobiological effectssuch as an “altered” storm of cytokines or effects on antigen-presenting cells are hypothesized. This could be of importance forfurther prevention strategies of acute GvHD and for maintenance of GvL-effect.

Author Disclosure: S. Schwarte, None; F. Bruns, None; J. Fruehauf, None; Y. Sorge, None; S. Skubich, None; M.W. Hoffmann,None.

2662 Radiation Guided Anti-P-Selectin Antibody to Tumor Microvascular Endothelium

G. Hariri1,2, Y. Zhang2, A. Fu2, Z. Han2, M. Brechbiel3, T. Peterson4, D. Hallahan1,2

1Vanderbilt University, Department of Biomedical Engineering, Nashville, TN, 2Vanderbilt University, Department ofRadiation Oncology, Nashville, TN, 3National Cancer Institute, Bethesda, MD, 4Vanderbilt University, Department ofRadiology, Nashville, TN

Purpose/Objective(s): Radiation induces translocation of P-selectin from storage reservoirs within the tumor endothelium tothe luminal surface of microvasculature. This radiation-inducible expression of P-selectin on tumor-associated endothelial cellscan be developed for tumor-targeted drug delivery. We developed specific antibodies against P-selectin, and tested feasibilityof delivering radioactive isotopes and drug-loaded nano-scale structures to irradiated tumors in vivo.

Materials/Methods: Single chain variable fragments (ScFv) of murine and human antibodies were selected by screeningphage-displayed ScFv libraries on purified P-selectin. The selected ScFvs were prioritized by affinity (ELISA and FMAT),specificity (cell and tissue staining), and stability. Prioritized antibodies were engineered for conjugating with different carriers,

S577Proceedings of the 48th Annual ASTRO Meeting