Radiobiologic studies of radioimmunotherapy and external beam radiotherapy in Vitro and in Vivo in human renal cell carcinoma xenografts

• Published in: Cancer 1997-12, Vol.80 (S12), p.2519-2528
• Main Authors: Ning, Shoucheng, Trisler, Kirk, Wessels, Barry W., Knox, Susan J.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Carcinoma, Renal Cell - radiotherapy; Female; human renal cell carcinoma xenograft; Humans; Kidney Neoplasms - radiotherapy; Medical sciences; Mice; Mice, Nude; monoclonal antibody; Neoplasm Transplantation; NR‐LU‐10; nude mice; Radiation therapy and radiosensitizing agent; Radiation Tolerance; radiobiology; Radioimmunotherapy; Radiotherapy Dosage; Tissue Distribution; Transplantation, Heterologous; Treatment with physical agents; Treatment. General aspects; Tumor Cells, Cultured; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/(SICI)1097-0142(19971215)80:12+<2519::AID-CNCR26>3.0.CO;2-E

BACKGROUND Previous studies suggest that the radiobiologic characteristics of in vitro survival curves are important determinants of the response of tumors to both conventional radiotherapy and radioimmunotherapy (RIT). The purpose of this study was to elucidate the relationship between in vitro radiation survival curve parameters and the relative sensitivity of tumor to RIT, exponentially decreasing low dose rate (ED LDR) irradiation and conventional high dose rate (HDR) fractionated external beam radiotherapy. METHODS Two human renal cell carcinoma cell lines, Caki‐1 and A498, were used in vitro and nude mouse xenograft studies. HDR external beam gamma irradiation (dose rate, 430 centigray [cGy]/minute) and ED LDR irradiation (initial dose rate, 22‐25 cGy/hour) were performed with a cesium‐137 (137Cs) gamma irradiator. RIT was carried out with yttrium‐90 (90Y)‐labeled monoclonal antibody NR‐LU‐10, and the absorbed radiation doses were calculated by medical internal radiation dose methodology. A clonogenic assay was used to generate radiation survival curves, and a computer FIT program was used to calculate the radiobiologic parameters. The antitumor efficacy of the different treatments was compared in vivo using a tumor regrowth delay assay in these two tumor xenograft models. RESULTS The radiation survival curves showed that the Caki‐1 cell line was more sensitive to both HDR and ED LDR irradiation than A498 in vitro. The Caki‐1 cell line, compared with A498, had a larger α (0.39 vs. 0.15 Gy following HDR and 0.32 vs. 0.21 Gy following ED LDR) and α‐to‐β ratio (6.92 vs. 2.60 Gy for HDR and 40.0 vs. 19.2 Gy for ED LDR), a smaller n number (5.13 vs. 23 for HDR and 1.16 vs. 3.53 for ED LDR), a lower quasi‐threshold dose (Dq) (1.60 vs. 3.15 Gy for HDR and 0.35 vs. 1.76 Gy for ED LDR), and a lower surviving fraction at 2 Gy (SF2) (0.37 vs. 0.60 for HDR and 0.51 vs. 0.61 for ED LDR), suggesting that Caki‐1, compared with A498, had a steep initial slope and a small shoulder. The final slope represented by the β value and Do dose (the dose (Gy) required to reduce the fraction of surviving cells of 37% of its previous value in the exponential region of the survival curves) did not vary significantly between these two cell lines at either HDR or ED LDR irradiation. Tumor volume doubling times were 4.0 ± 1.5 days for Caki‐1 and 4.2 ± 1.8 days for A498 tumor xenografts. One hundred μCi/50 μg of 90Y‐labeled, isotype‐matched irrelevant monoclonal antibody CCOO16‐3 pr