PET Radioimmunoscintigraphy of Renal Cell Cancer Using 89 Zr-Labeled cG250 Monoclonal Antibody in Nude Rats

Abstract

Introduction

: With the introduction of positron-emitting radionuclides with half-lifes in days, such as ⁸⁹Zr and ¹²⁴I, radioimmunoscintigraphy (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 ⁸⁹Zr (immuno-PET) or ¹¹¹In (RIS), and [¹⁸F]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 ¹¹¹InDTPA-cG250, 20 MBq ⁸⁹Zr-Df-cG250 or 4 MBq [¹⁸F]FDG. Planar ¹¹¹In-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 [¹⁸F]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 37°C, and the immunoreactivity was preserved. Two (2) days after injection, s.c. tumors (100 mg) were clearly visualized, both with ⁸⁹Zr-Df-cG250 and ¹¹¹In-DTPA-cG250. Tumors were not visualized with [¹⁸F]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 ⁸⁹Zr-Df-cG250 and ¹¹¹In-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 ± 0.7 %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 ⁸⁹Zr, while preserving the immunoreactivity of the moAb. In this rat model, the in vivo biodistribution of ⁸⁹Zr-Df-cG250 was identical to that of ¹¹¹In-DTPA-cG250. Immuno-PET of RCC is feasible with ⁸⁹Zr-cG250, and relatively small tumors could be visualized, even without a dedicated PET camera for small animals.