Radiolabeled antibodies in renal cell carcinoma

Abstract

Renal cell carcinoma (RCC) is a radio- and chemotherapy resistant tumor, which has a very high morbidity and mortality when metastasized. The current treatment options demonstrate limited efficacy and severe side-effects. Therefore, there is a need for new therapeutic strategies for RCC. As for other malignancies, monoclonal antibodies (mAbs) targeting tumor-associated antigens have been developed for RCC. One of these, mAb G250, targets the MN/CAIX/G250 antigen, which is ubiquitously expressed in clear cell RCC (ccRCC). ccRCC is the most common form of RCC with a prevalence of 80%. Expression of G250 in normal tissue is restricted to the gastrointestinal mucosa and related structures, thereby making it a suitable candidate for targeting ccRCC. In several clinical studies the efficient accumulation of mAb G250 in ccRCC has been demonstrated, resulting in high contrast images. G250-imaging could prove to be a valuable tool in diagnosing metastases in patients with a G250-antigen positive primary tumor and/or in the differential diagnosis of suspect kidney lesions. Furthermore, the therapeutic efficacy of radiolabeled G250 has been investigated in a series of studies. Thus far, most efforts have been devoted to G250 labeled with high doses of 131I. Other radionuclides which may enhance the therapeutic index of this radiolabeled mAb are currently under investigation. In our institution, an activity dose escalation study is currently ongoing to investigate the therapeutic potential of 177Lu-labeled G250 in metastatic ccRCC patients. In this review, the current status of the diagnostic and therapeutic properties of radiolabeled antibodies in RCC is described.

Figure 1

(a) [¹¹¹In]cG 250 immunoscintigram of a patient with metastatic ccRCC, acquired 6 days after injection of 185 MBq of [¹¹¹In]cG250. Black arrows mark the RCC lesions. Green arrows mark a lesion not seen on the fluorodeoxyglucose (FDG)-positron emission tomography (PET)-computed tomography(CT) images shown in (b). Red arrows indicate the injection standard. The anterior image is shown in the left panel, the posterior image is shown in the right panel. (b) PET-CT scan of the same patient acquired after injection of 250 MBq of [¹⁸F]FDG.