ST2146biot is a biotinylated anti-
tenascin monoclonal antibody (mAb) to be used for Pretargeted Antibody Guided
Radioimmunotherapy (PAGRIT) of solid
tumors. In vivo biodistribution studies of (125)I-labeled
ST2146biot were done in nude mice transplanted with human HT-29 colon
carcinoma and/or human U-118MG
glioblastoma cells characterized for low and high
tenascin expression, respectively. In vitro results show that ST2146 retains immunoreactivity upon biotinylation, in contrast to other anti-
tenascin mAbs. In vivo biodistribution of ST2146 shows specific
tumor accumulation up to 10 days after the i.v. injection, with no relevant differences between biotinylated and nonbiotinylated ST2146. A dose of 4 microg/mouse saturates the low
tenascin-expressing human colon
carcinoma HT-29, whereas the high
tenascin-expressing human
glioblastoma U-118MG seems to be saturated at a
ST2146biot dose between 320 and 640 microg/mouse. The percentage of injected dose per gram of
tumor ranges from 10% to 30%, corresponding to an amount of
ST2146biot/g of
tumor of approximately 400 ng/g and >200 microg/g for HT-29 and U-118MG, respectively.
Tumor to normal organs uptake ratios are between 15 and 60, confirming high
tumor selectivity of
ST2146biot despite its cross-reactivity with the
tenascin expressed at low level in the normal mouse organs. The
ST2146biot localization data are substantially confirmed even when both low and high
tenascin-expressing
tumors are implanted in the same animal. To our knowledge, the absolute amount of
ST2146biot, specifically localized in xenotransplanted human
tumors, is the highest thus far described and supports the clinical use of this mAb in PAGRIT(R).