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Purpose: ED-B fibronectin is expressed only during angiogenic processes and in tissues undergoing growth and/or extensive remodeling. We demonstrated previously the possibility to target and selectively deliver therapeutic substances to tumor vasculature in experimental animal models using a human recombinant antibody fragment, L19, specific for the ED-B domain of fibronectin. Here we evaluate the possibility of targeting primary tumors and metastatic lesions in cancer patients through immunoscintigraphy using (123)I-labeled dimeric L19 [L19(scFv)(2)]., Experimental Design: Twenty patients (34-79 years of age) with lung, colorectal, or brain cancer, whose tumors had been confirmed by imaging techniques and/or histologically, were admitted to the immunoscintigraphic investigation., Results: The dimeric L19 antibody selectively localized in tumor lesions in aggressive types of lung cancer and colorectal cancer. Because ED-B fibronectin is expressed only during angiogenic processes and in tissues undergoing growth and/or extensive remodeling, L19(scFv)(2) is able to distinguish between quiescent and actively growing lesions. No side effects were observed., Conclusions: The ability of L19(scFv)(2) to target tumors in patients provides the foundations for new therapeutic applications, in which the L19 antibody is engineered to selectively deliver bioactive molecules to primary tumors as well as to metastases.

Within the Italian CNR Biomedical Technology programmes a large multicentre clinical trial on CEA-expressing carcinomas has been carried out. F(ab')2 fragments of anti-CEA monoclonal antibody (MAb) FO23C5, radiolabelled with either 131I or 111In, were supplied to 10 different Italian nuclear medicine departments. Over 500 patients with gastrointestinal, lung, breast, and other carcinomas have been investigated. The results obtained in our nuclear medicine department are reported here. In GI cancer group, the 131I compound showed better results except in liver metastases detected only in 28/57 patients. In the lung cancer group, very satisfactory results were achieved in primary tumours and local or systemic recurrences: 111In tracer was preferentially used. In the breast cancer group immunoscintigraphy proved to be helpful in differential diagnosis of neoplastic and benign bone lesions. Significant improvements of diagnostic sensitivity were achieved in GI cancer patients by means of i.p. administration. Finally, 12 patients with advanced disease were given different 131I radioiodinated MAbs (100 mCi average dose). Administration route was either i.v. (3 cases) or i.p. (9 cases). Clinical and instrumental evidence of complete (1) or partial (7) response was observed in 8 patients.