Results of a phase II trial of novel carbonic anhydrase IX radiotracer 18F-VM4-037 in renal cell carcinoma.

LBA400 Background: Carbonic Anydrase IX (CAIX) has been identified as a potential marker for clear cell renal cell carcinoma (ccRCC). We report the results of a phase II clinical trial of a novel small molecule radiotracer that binds to CAIX in clinically localized kidney tumors or biopsy proven metastases. Methods: Between October 2012 and May 2013, patients with kidney tumors underwent imaging with the 18F-VM4-037 radiotracer within 4 weeks of biopsy or surgery for kidney tumors. Imaging characteristics with the radiotracer were collected. All H&E pathology was centrally reviewed by a single pathologist. Immunohistochemistry of the surgical specimens for CAIX and Carbonic Anhydrase XII (CAXII) was reviewed by two experienced pathologists. Primary objectives were to evaluate the biodistribution of the radiotracer within tumor and non-tumor tissues as well to assess the safety of the radiotracer in patients. Results: 12 patients were enrolled and 11 received radiotracer and images were obtained. All patients tolerated the radiotracer well with no significant adverse events. 10 of the 11 patients had histologically confirmed malignancy. 1 patient had a complex cyst with no tumor found at surgery. Two patients had extrarenal disease and 9 had tumors in the kidney only. 100% had ccRCC and 4/11 had germline VHL mutations. Mean SUV for the entire group as 5.44 in the index lesions; in patients with histologically confirmed ccRCC the mean SUV was 5.91. 12 samples were stained for CAIX and CAXII including a biopsy obtained from a lung metastasis in one patient. The concordance between pathologists for CAIX IHC was 75%, for CAXII was 67%. Of the CAIX IHC slides, 67% had 3+ staining, 25% had 2+ and one specimen did not demonstrate CAIX staining. Only one specimen demonstrated 3+ staining for CAXII; 2 specimens had no detectable staining for CAXII and the remainder stained 1-2+ for CAXII. Conclusions: The 18F-VM4-037 was well tolerated and demonstrated modest signal uptake in tumors within the kidney. Immunohistochemistry staining for CAIX and CAXII was robust in nearly all tumors making correlation with radiotracer signal difficult. Larger studies are needed to evaluate the diagnostic performance of this radiotracer. Clinical trial information: NCT01712685.