Development of radioimmunoconjugate for diagnosis and management of head-and-neck subclinical cancer and colorectal carcinoma

• Published in: Brazilian Journal of Pharmaceutical Sciences 2017-01, Vol.53 (4)
• Main Authors: Benedetto, Raquel, Massicano, Adriana Vidal Fernandes, Silva, Jefferson Jesus, Boas, Cristian Antonio Wieczorek Villas, Mengatti, Jair, Araújo, Elaine Bortoleti de
• Format: Article
• Language: English
• Subjects: 111In; Cancer therapies; Cetuximab; Colorectal cancer; Head & neck cancer; Head and neck cancer/diagnosis; Hypoxia; Immunotherapy; Indium; Molecular weight; Monoclonal antibodies; PHARMACOLOGY & PHARMACY; Radioimmunoconjugate/development; SPECT; Targeted cancer therapy; Tumors; Tumors diagnosis
• ISSN: 2175-9790; 1984-8250; 2175-9790
• DOI: 10.1590/s2175-97902017000417039

Scientific innovations in diagnostic methods are important drivers of cancer control and prevention. Noninvasive imaging of the epidermal growth factor receptor (EGFR) in head-and-neck squamous, cell carcinoma and colorectal cancer could be valuable to select patients for EGFR-targeted therapy, as well as to monitor the efficacy and occurrence of resistance to immunotherapy. In order to develop the first Brazilian radioimmunoconjugate for diagnosis, Cetuximab has been conjugated to p-SCN-Bn-DTPA chelator and radiolabeled with Indium-111. The conjugation methodology was optimized using different mAb:DTPA molar ratios, time was then reduced for immunoconjugate preparation, besides the protein recovery’ percentage increased after purification (m = 83.8 ± 0.91 %). The stability of Cetuximab-DTPA at - 20 oC was evaluated for six months, and its integrity was greater than 90% (m =93.9 ± 1.5%, N = 24). The radioimmunoconjugate with specific activity of 185 MBq/mg showed radiochemical purity above 95% (m=96.8 ± 1.31 %, N = 15). We conclude that the radioimmunoconjugate 111In-DTPA-cetuximab is stable and may be applied to the diagnosis of EGFR-positive tumors.