Pancreas carcinoma is responsible for more than 30% of tumor-related death because it is notoriously difficult to diagnose; thus, new diagnostic approaches are imperatively needed. Recently, prostate stem cell antigen (PSCA) and mesothelin demonstrated high expression and wide distribution in pancreatic cancer, but not in normal pancreas. This research aims to develop new radioimmunoconjugates (RICs) for pancreatic cancer detection based on monoclonal antibodies (mAb) to PSCA and mesothelin, which are heavily overexpressed in this tumor histotype. Either mAbs labeled with fluorophore exhibited high recognition capacity for Ag + tumor-cells both in vitro and in vivo, as assessed by cytometry analysis and optical imaging. 99mTc-radioimmunoconjugates were obtained with high labelling efficiency (98%), by reduction of both mAbs with 2-mercaptoethanol and incubation with 99mTcO4- in presence of a weak competition ligand. Stability tests performed in saline solution and human serum demonstrated that RICs are stable for at least 48 h. Both mAbs were radiolabeled by direct method with a high radiochemical efficiency and stability, and could be used for pancreatic cancer detection. This research was supported by AIRC (IG-13121 to A.R.).
New Tc-99m-radioimmunoconjugates for pancreatic carcinoma detection
Bolzati Cristina;Salvarese Nicola;
2014
Abstract
Pancreas carcinoma is responsible for more than 30% of tumor-related death because it is notoriously difficult to diagnose; thus, new diagnostic approaches are imperatively needed. Recently, prostate stem cell antigen (PSCA) and mesothelin demonstrated high expression and wide distribution in pancreatic cancer, but not in normal pancreas. This research aims to develop new radioimmunoconjugates (RICs) for pancreatic cancer detection based on monoclonal antibodies (mAb) to PSCA and mesothelin, which are heavily overexpressed in this tumor histotype. Either mAbs labeled with fluorophore exhibited high recognition capacity for Ag + tumor-cells both in vitro and in vivo, as assessed by cytometry analysis and optical imaging. 99mTc-radioimmunoconjugates were obtained with high labelling efficiency (98%), by reduction of both mAbs with 2-mercaptoethanol and incubation with 99mTcO4- in presence of a weak competition ligand. Stability tests performed in saline solution and human serum demonstrated that RICs are stable for at least 48 h. Both mAbs were radiolabeled by direct method with a high radiochemical efficiency and stability, and could be used for pancreatic cancer detection. This research was supported by AIRC (IG-13121 to A.R.).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
