PET radioimmunoscintigraphy of renal cell cancer using 89Zr-labeled cG250 monoclonal antibody in nude rats

Introduction: With the introduction of positron-emitting radionuclides with half-lifes in days, such as Zr-89 and I-124, radioinummoscintigraphy (RIS) with positron-emitter-labeled monoclonal antibodies (moAbs) becomes feasible. RIS, using positron emission tomography (immuno-PET), combines the specific localization of an antibody with the high resolution of a PET camera. In the present study, scintigraphic tumor imaging using chimeric moAb G250 labeled with Zr-89 (immuno-PET) or (111')n (RIS), and [F-18]FDG-(PET) was explored in rats with s.c. renal cell carcinoma (RCC) tumors. Methods: Nude rats (6-8 rats per group) with s.c. SK-RC-52 tumors were i.v. injected with 4 MBq In-111-DTPA-cG250, 20 MBq Zr-89-Df-cG250 or 4 MBq [F-18]FDG. Planar In-111-DTPA-cG250 images were obtained 5 minutes, and 24, 48, and 72 hours postinjection (p.i.). 3D PET imaging was performed 5 minutes, and 24, 48, and 72 hours after a 89Zr-Df-cG250 injection and 1 hour after a [F-18]FDG injection using a Siemens ECAT EXACT PET camera. Rats were killed after the last imaging session, and the uptake of the radiolabel in the dissected tissues was determined. Results: Both radiolabeled antibody preparations were stable during 4 days of incubation in serum at 37degreesC, and the immunoreactivity was preserved. Two (2) days after injection, s.c. tumors (100 mg) were clearly visualized, both with Zr-89-Df-cG250 and In-111-DTPA-cG250. Tumors were not visualized with [F-18]FDG (uptake in tumor of 0.5 +/- 0.1%ID/g, 1 hour p.i.). The biodistribution experiments showed an identical uptake in the tumor for both Zr-89-Df-cG250 and In-111-DTPA-cG250 at 3 days p.i. (5.0 +/- 2.4 and 4.9 +/- 2.9%ID/g, respectively). Blood levels at 3 days p.i. were also identical (1.4 +/- 0.4 versus 1.7 +/- 10.7%ID/g), and no significant differences were found in the biodistribution of normal tissues between the two radiolabeled cG250 preparations. Conclusion: The cG250 antibody can be stably labeled with the positron-emitter Zr-89, while preserving the inummoreactivity of the moAb. In this rat model, the in vivo biodistribution of Zr-89-Df-cG250 was identical to that of. In-DTPA-cG250. Immuno-PET of RCC is feasible with Zr-89-cG250, and relatively small tumors could be visualized, even without a dedicated PET camera for small animals.