ImmunoPET Imaging of Renal Cell Carcinoma with 124 I- and 89 Zr-Labeled Anti-CAIX Monoclonal Antibody cG250 in Mice

Abstract

Introduction:

Monoclonal antibody (mAb) cG250 recognizes carbonic anhydrase IX (CAIX), overexpressed on clear cell renal cell carcinoma (ccRCC). ¹²⁴I-cG250 is currently under clinical investigation for the detection of ccRCC. However, the ¹²⁴I label is rapidly excreted from the tumor cells after internalization of the radiolabeled mAb. We hypothesized that labeling cG250 with the residualizing positron emitter ⁸⁹Zr would lead to higher tumor uptake and more sensitive detection of ccRCC lesions.

Materials and Methods:

Nude mice with CAIX-expressing ccRCC xenografts (SK-RC-52 or NU-12) were i.v. injected with ⁸⁹Zr-cG250 or ¹²⁴I-cG250. To determine specificity of ⁸⁹Zr-cG250 uptake in ccRCC, one control group was i.v. injected with ⁸⁹Zr-MOPC21 (irrelevant mAb). PET images were acquired using a small animal PET camera and the biodistribution of the radiolabeled mAb was determined.

Results:

The ccRCC xenografts were clearly visualized after injection of ⁸⁹Zr-cG250 and ¹²⁴I-cG250. Tumor uptake of ⁸⁹Zr-cG250 was significantly higher compared with ¹²⁴I-cG250 in the NU-12 tumor model (114.7%±25.2% injected dose per gram (%ID/g) vs. 38.2±18.3%ID/g, p=0.029), but in the SK-RC-52 the difference in tumor uptake was not significant (48.7±15.2%ID/g vs. 32.0±22.9%ID/g, p=0.26). SK-RC-52 tumors were not visualized with ⁸⁹Zr-MOPC21 (tumor uptake 3.0%ID/g). Intraperitoneal SK-RC-52 lesions as small as 7 mm³ were visualized with ⁸⁹Zr-cG250 PET.

Conclusion:

ImmunoPET imaging with cG250 visualized s.c. and i.p. ccRCC lesions in murine models. This confirms the potential of cG250 immunoPET in the diagnosis and (re)staging of ccRCC. PET imaging of ccRCC tumors with ⁸⁹Zr-cG250 could be more sensitive than ¹²⁴I-cG250-PET.