Comparative evaluation of affibody- and antibody fragments-based CAIX imaging probes in mice bearing renal cell carcinoma xenografts

• Published in: Scientific reports 2019-10, Vol.9 (1), p.14907, Article 14907
• Main Authors: Garousi, Javad, Huizing, Fokko J., Vorobyeva, Anzhelika, Mitran, Bogdan, Andersson, Ken G., Leitao, Charles Dahlsson, Frejd, Fredrik Y., Löfblom, John, Bussink, Johan, Orlova, Anna, Heskamp, Sandra, Tolmachev, Vladimir
• Format: Article
• Language: English
• Subjects: 13/1; 59; 631/61/51/2318; 692/4028/67/2321; 692/53/2423; 82; 82/80; 82/83; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Biodistribution; Bone imaging; Carbonic Anhydrase IX - antagonists & inhibitors; Carbonic Anhydrase IX - immunology; Carbonic Anhydrase IX - metabolism; Carbonic anhydrases; Carcinoma, Renal Cell - diagnostic imaging; Carcinoma, Renal Cell - pathology; Cell Line, Tumor; Fab; Female; Humanities and Social Sciences; Humans; Hypoxia; Immunoglobulin Fragments - administration & dosage; Immunoglobulin Fragments - immunology; Immunoglobulin Fragments - pharmacology; Indium Radioisotopes; Kidney cancer; Kidney Neoplasms - diagnostic imaging; Kidney Neoplasms - pathology; Labeling; Mass spectrometry; Metastases; Metastasis; Mice; Molecular Imaging - methods; Molecular Probes - administration & dosage; Molecular Probes - chemistry; Molecular Probes - immunology; Molecular Probes - pharmacology; Monoclonal antibodies; multidisciplinary; Proteins; Radiation; Radioactive Tracers; Renal cell carcinoma; Science; Science (multidisciplinary); Scientific imaging; Single Photon Emission Computed Tomography Computed Tomography - methods; Tissue Distribution; Tumors; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-51445-w

Carbonic anhydrase IX (CAIX) is a cancer-associated molecular target for several classes of therapeutics. CAIX is overexpressed in a large fraction of renal cell carcinomas (RCC). Radionuclide molecular imaging of CAIX-expression might offer a non-invasive methodology for stratification of patients with disseminated RCC for CAIX-targeting therapeutics. Radiolabeled monoclonal antibodies and their fragments are actively investigated for imaging of CAIX expression. Promising alternatives are small non-immunoglobulin scaffold proteins, such as affibody molecules. A CAIX-targeting affibody ZCAIX:2 was re-designed with the aim to decrease off-target interactions and increase imaging contrast. The new tracer, DOTA-HE 3 -ZCAIX:2, was labeled with 111 In and characterized in vitro . Tumor-targeting properties of [ 111 In]In-DOTA-HE 3 -ZCAIX:2 were compared head-to-head with properties of the parental variant, [ 99m Tc]Tc(CO) 3 -HE 3 -ZCAIX:2, and the most promising antibody fragment-based tracer, [ 111 In]In-DTPA-G250(Fab’) 2 , in the same batch of nude mice bearing CAIX-expressing RCC xenografts. Compared to the 99m Tc-labeled parental variant, [ 111 In]In-DOTA-HE 3 -ZCAIX:2 provides significantly higher tumor-to-lung, tumor-to-bone and tumor-to-liver ratios, which is essential for imaging of CAIX expression in the major metastatic sites of RCC. [ 111 In]In-DOTA-HE 3 -ZCAIX:2 offers significantly higher tumor-to-organ ratios compared with [ 111 In]In-G250(Fab’) 2 . In conclusion, [ 111 In]In-DOTA-HE 3 -ZCAIX:2 can be considered as a highly promising tracer for imaging of CAIX expression in RCC metastases based on our results and literature data.