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In Vivo and In Vitro Characterizations of Three ^99mTc-Labeled Monoclonal Antibody G250 Preparations

Departments of Urology and Nuclear Medicine, University Hospital Nijmegen, Nijmegen, The Netherlands

Correspondence: For correspondence or reprints contact: Otto C. Boerman, PhD, Department of Nuclear Medicine, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

ABSTRACT

In previous clinical studies, excellent visualization of tumor lesions has been observed with ¹³¹I-labeled monoclonal antibody (mAb) G250 in patients with renal cell carcinoma (RCC). In several cases, ¹³¹I-cG250 immunoscintigraphy disclosed tumor lesions that were not visualized by radiography or CT. To improve image quality, we aimed to develop a ^99mTc-labeled mAb G250 preparation for radioimmunodetection of RCC. We studied in vitro stability, biodistribution and imaging potential of three ^99mTc-labeled G250 preparations in nude mice with subcutaneous RCC xenografts. ¹²⁵I-G250 and the nonspecific mAb ¹³¹I-MN14 were used as control antibodies. Methods: The mAb G250 was labeled with ^99mTc according to three methods using: (a) S-hydrazinonicotinamide (HYNIC), (b) S-benzoylmercaptoacetyltriglycine (MAG3) and (c) a direct labeling method (Schwarz method). The stability of all preparations was tested in serum at 37°C during 48 h. In addition, diethylenetriamine pentaacetic acid, cysteine and glutathione challenge assays were performed. Results: All preparations showed good stability in serum during the 48-h incubation period. ^99mTc-G250 (Schwarz) showed release of the radiolabel at a 100-fold or higher molar excess of cysteine and at a 10,000-fold or higher molar excess of glutathione. ^99mTc-MAG3-G250 showed release of the radiolabel at a 10,000-fold molar excess of cysteine. ^99mTc-HYNIC-G250 was stable under all conditions. Tumors were clearly visualized with all preparations. ^99mTc-G250 (Schwarz) showed significantly lower blood levels (3.8 %ID/g) compared with all other preparations (11.2, 13.4 and 13.4 %ID/g for ^99mTc-HYNIC-G250, ^99mTc-MAG3-G250 and ¹²⁵I-G250, respectively, 48 h postinjection). At 48-h postinjection, mean tumor uptake was very high with all mAb G250 preparations: 92.4 (^99mTc-HYNIC-G250), 125.9 (^99mTc-MAG3-G250), 29.4 (^99mTc-G250 Schwarz) and 75.4 (¹²⁵I-G250) %ID/g. Mean tumor uptake of the nonspecific ¹³¹I-MN14 mAb was 6.6 %ID/g. Conclusion: In this study, ^99mTc-HYNIC-G250 showed excellent in vitro stability and tumor targeting. Moreover, this preparation could be labeled with high efficiency (>95%) at room temperature within 15 min. Therefore, ^99mTc-HYNIC-G250 seems to be an ideal candidate for radioimmunodetection of RCC.

Key Words: monoclonal antibody G250 • renal cell carcinoma • radioimmunodetection • mercaptoacetyltriglycine • hydrazinonicotinamide

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