Inert coupling of IRDye800CW to monoclonal antibodies for clinical optical imaging of tumor targets

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Engineering and characterisation of chimeric monoclonal antibody 806 (ch806) for targeted immunotherapy of tumours expressing de2-7 EGFR or amplified EGFR

We report the generation of a chimeric monoclonal antibody (ch806) with specificity for an epitope on the epidermal growth factor receptor (EGFR) that is different from that targeted by all other anti-EGFR therapies. Ch806 antibody is reactive to both de2-7 and overexpressed wild-type (wt) EGFR but not native EGFR expressed in normal tissues at physiological levels. Ch806 was stably expressed in CHO (DHFR −/−) cells and purified for subsequent characterisation and validated for use in preliminary immunotherapy investigations. Ch806 retained the antigen binding specificity and affinity of the murine parental antibody. Furthermore, ch806 displayed enhanced antibody-dependent cellular cytotoxicity against target cells expressing the 806 antigen in the presence of human effector cells. Ch806 was successfully radiolabelled with both iodine-125 and indium-111 without loss of antigen binding affinity or specificity. The radioimmunoconjugates were stable in the presence of human serum at 37°C for up to 9 days and displayed a terminal half-life (T1/2β) of approximately 78 h in nude mice. Biodistribution studies undertaken in BALB/c nude mice bearing de2-7 EGFR-expressing or amplified EGFR-expressing xenografts revealed that 125I-labelled ch806 failed to display any significant tumour retention. However, specific and prolonged tumour localisation of' 111In-labelled ch806 was demonstrated with uptake of 31%ID g−1 and a tumour to blood ratio of 5 : 1 observed at 7 days postinjection. In vivo therapy studies with ch806 demonstrated significant antitumour effects on established de2-7 EGFR xenografts in BALB/c nude mice compared to control, and both murine 806 and the anti-EGFR 528 antibodies. These results support a potential therapeutic role of ch806 in the treatment of suitable EGFR-expressing tumours, and warrants further investigation of the potential of ch806 as a therapeutic agent

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

Antibody therapy in renal cell carcinoma.

Contains fulltext : 69826.pdf (publisher's version ) (Open Access)The treatment of metastasized renal cell carcinoma (RCC) still represents a formidable challenge, despite the development of small molecule, tyrosine kinase inhibitors (TKI) that have made a major impact on the disease. Although the percentage of patients achieving a partial response or stabilization of disease has been impressive, these effects are mostly non-durable. Additionally, drug-related side effects can be quite severe. Alternative treatment modalities might be monoclonal antibodies (mAbs). mAbs against RCC-associated antigens have been developed and have shown promise. Additionally, current efforts focus on Bevacizumab that recognizes vascular endothelial growth factor (VEGF). VEGF overexpression in RCC provides the opportunity to inhibit this proangiogenic pathway. Also with Bevacizumab, promising results have been obtained, particularly in combination with other treatment modalities. It is likely that mAbs, either as single agents or in combination with other agents, may become useful additions to the armamentarium to diagnose and treat RCC