P104 Radioimmunotherapy of Head and Neck Cancer Xenografts Using 131I-L19-SIP for Selective Targeting of Tumor Vasculature

New Strategy for the Extension of the Serum Half-Life of Antibody Fragments

“…Indeed, F9 tumors have a doubling time of approximately 1-2 days (34), with the result that the antibody dose in the tumor mass gets "diluted" while the neoplastic mass increases in size. The maximal antibody uptake in the tumor was observed at 48 h (25%ID/g and 64%ID/g in the absence or presence of the correction for tumor growth, respectively; Figure 4A,C), but in general, we observed an excellent antibody retention at the tumor site, in line with previous preclinical and clinical studies obtained with antibodies specific to the extradomain B (EDB) of fibronectin (30,(36)(37)(38)(39). From the data of Figure 4A, blood clearance can be fitted with a single exponential, corresponding to a half-life of 1000 min.…”

“…The observation that antibody uptake in the tumor grows as a consequence of a corresponding increase of serum half-life is in line with the results of previous biodistribution studies, in which the targeting properties of antibodies in different formats (e.g., scFv, mini-antibody, IgG) were compared (30,37,38,40,41). Similarly, chemical modification of antibody fragments with PEG or polysialic acid polymers has previously been shown to considerablyextendserumhalf-livesandtumoruptakevalues (13)(14)(15).…”

Human monoclonal antibodies targeting carbonic anhydrase IX for the molecular imaging of hypoxic regions in solid tumours

“…With this radiometal, we observed high kidney and liver values (Table 2), similar to what we had previously reported for the 177 Lu-labelled L19 antibody in SIP format (Tijink et al, 2006). In the pairwise comparison presented in this article, L19 appeared to yield higher tumour uptake values, yet at the expense of a slower blood clearance.…”

Comparative immunohistochemistry of L19 and F16 in non-small cell lung cancer and mesothelioma: Two human antibodies investigated in clinical trials in patients with cancer

“…In animals, immunohistochemical analysis of normal lung reveals no detectable staining using antibodies specific to oncofetal fibronectin or tenascin-C [12,[57][58][59]. This is consistent with the observation of no preferential uptake of L19 or F16 in normal lung in biodistribution studies [12,15,27,35,38,60].…”