Introduction: EGFR is a transmembrane protein related to the tyrosine kinase receptor family. An increased expression of EGFR is the hallmark of many human tumors, such as breast cancer, squamous-cell carcinoma of the head and neck, and prostate cancer. Cetuximab (C225, ErbituxR, an IgG1 class) targeting the EGFR is the first mAb targeted against EGFR receptors approved by the FDA for metastatic colorectal carcinoma. The overall goal of this study was to evaluate 64Cu labeled DOTA-Cetuximab to image EGFR positive breast cancer in athymic nude mice bearing MDA-MB-468.Methods: Cetuximab was conjugated with DOTA, purified by molecular filtration and concentration was determined spectrophotometrically. DOTA-Cetuximab was labeled with 64Cu and radiochemical yield was determined by HPLC. The binding affinity of 64Cu - DOTA-Cetuximab to MDA-MB-468 was determined in the presence of 0.05-10 nM of unlabeled Cetuximab. The athymic nude mice bearing MDA-MB-468 (~5×106) xenografts were given, 64Cu - DOTA-Cetuximab i.v., (50 ± 6.1mCi, 4 hr group, n=5, 200 ± 22.7mCi, 24 hr group, n=5). Animals were then imaged, sacrificed and quantitative tissue distribution was performed. In order to assess tumor uptake is mediated by EGFR-receptors expression, biodistribution study was done with blocking unlabeled Cetuximab.Results: The radiochemical yield was 97.1 ± 1.1% with the specific activity of 923 Ci/mM Cetuximab.64Cu- DOTA-Cetuximab showed high affinity to EGFR-positive MB-468 cells (KD of 0.4 nM). Both biodistribution and microPET imaging studies with 64Cu - DOTA-Cetuximab demonstrated higher tumor uptake at 24 hr (21.91% ± 0.86% ID/g) as compare to at 4 hr (12.33% ± 0.41% ID/g). Excellent PET images were obtained.Conclusion: 64Cu - DOTA-Cetuximab is worthy of further investigation to target EGFR for imaging breast cancer.

Background: Cetuximab is a monoclonal antibody which acts against the epidermal growth‑factor receptor. Randomized controlled trials show that the addition of cetuximab to folinic acid, 5‑flourouracil, irinotecan (FOLFIRI), folinic acid, 5‑flourouracil, oxaliplatin (FOLFOX) and capecitabin + oxaliplatin (CAPOX) regimens, as the first‑line treatment for metastatic colorectal cancer (CRC), increases the overall survival (OS) and progression‑free survival (PFS) compared to FOLFIRI, FOLFOX and CAPOX regimens alone. The aim of this study was to analyze the cost‑effectiveness of different treatment programs for managing metastatic CRC with and without cetuximab in the first‑line treatment of unresectable metastatic CRC in Iran.Methods: A systematic search of the literature was performed in PubMed, Centre for Reviews and Dissemination Databases and Cochrane Library to assess the effectiveness of the drug in the context of PFS, OS and the adverse events. The incremental cost‑effectiveness ratio of each treatment program was calculated. An extensive sensitivity analysis was conducted on the results regarding the effectiveness.Results: The addition of cetuximab to FOLFIRI, FOLFOX and CAPOX programs increased PFS by 0.1, 0.042 and 0.042 years, respectively. Similarly, the addition of cetuximab to FOLFIRI, FOLFOX and CAPOX increased OS by 0.325, 0.442 and 0.442 years and also cost $212825, $202484 and $204198 individually. Whereas, based on the World Health Organisation (WHO) suggested threshold for cost‑effectiveness analysis, even FOLFOX + cetuximab was very higher than the threshold in Iran (37.4 times higher).Conclusions: The FOLFOX regimen + cetuximab provides lower costs per additional life years gained (more cost‑effective) compared with its alternatives in the treatment of patients with unresectable metastatic CRC. However, according to the WHO indicator, none of the cetuximab regimens could be considered as cost effective for the Iranian health care market.

Objective: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Engineeredbiomolecules can be used as a targeted tool to deliver drugs directly to tumors that reduce the adverse effects of conventionaltreatments. We aimed to prepare non-targeted oxaliplatin-loaded chitosan nanoparticles (OXPT-CS NPs) and targetedOXPT-CS NPs decorated with cetuximab single-chain variable fragment (scFv) to send both NPs to epidermal growth factorreceptor (EGFR) overexpressing HCT 116 cells, a human colorectal carcinoma cell line, for comparing their cytotoxicity.Materials and Methods: In this experimental study, OXPT-CS NPs were synthesized using a fluid system. Encapsulationefficiency percentage (EE%) and oxaliplatin release rate were evaluated. Western blot and cell-based ELISA confirmed scFvproduction and its binding ability to EGFR, respectively. The Fourier transform infrared spectroscopy (FTIR) determinedthe conjugation of scFv to OXPT-CS NPs. The NPs were characterized, and their toxicity against the HCT 116 cells wasevaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and flow cytometry assays.Results: The EE% of OXPT-CS NPs was 93%, and the average diameters were 75.85 ± 8.81 nm and 92.48 ± 9.51before and after scFv conjugation, respectively. The scFv was purified via affinity chromatography. The western blotmethod and cell-based ELISA revealed successful purification of scFv and its attachment to EGFR on HCT 116 cells.The FTIR analysis determined the interactions between the scFv and OXPT-CS NPs. According to MTT and flowcytometry results, the targeted delivery system significantly reduced HCT 116 cancer cell viability and increasedapoptosis induction up to 99.8%.Conclusion: The scFv-OXPT-CS NPs demonstrated an increased cytotoxic function due to the presence of scFv in itsformulation. This delivery system offers a promising method for delivering chemotherapy drugs to cancer cells. Moreresearch is needed on the best strategies for improving treatment efficacy by targeting cancer cells.