131I-Radretumab (131I-L19-SIP, 131I-L19SIP) has been explored as both a tumor-imaging agent and a radioimmunotherapy (RIT) drug. The drug was developed by the Italian company Philogen SpA in collaboration with initially Schering Pharma, then Bayer Schering Pharma AG.
L19-SIP (Radretumab) is a human recombinant antibody fragment consisting of the variable regions of the L19 mAb directed against the extra-domain B (ED-B) of fibronectin that is overexpressed in tumoral vasculature. Fibrogen is expressed during angiogenesis. These molecules can target tumor neovasculature, and are also relevant to other disorders related to angiogenesis, such as rheumatoid arthritis and age-related macular degeneration. 131I-L19-SIP is the most advanced radiolabeled drug. First positive results in human trials were obtained at doses of 2–6 mCi for diagnostics and 100–150 mCi for therapy. The same molecule labeled with iodine-124 (124I- L19SIP) was explored in humans to predict doses delivered to tumor lesions and healthy organs by a subsequent Radretumab RIT in patients with brain metastases from solid cancer. Immuno-PET with 124I-L19-SIP showed significant advantages over conventional 131I imaging, in particular accuracy of dosimetric results.
Clinical Phase I/II studies were performed with solid tumor patients such as colorectal cancer, melanoma, thymoma, mesothelioma, prostate cancer, pancreatic cancer and lymphomas. A clinical benefit was seen in several patients. This led to the conclusion that large-scale trials are needed to confirm these preliminary data. The molecule showed good tolerability and high tumor uptake combined with low red marrow absorbed dose. 131I-L19-SIP is in Phase II development in brain metastases, lung cancer and HD.