Figure 2.

In vivo PET imaging of CD146 expression and ex vivo biodistribution of ⁸⁹Zr-Df-YY146 in mice bearing subcutaneous HCC xenografts. A) Representative maximum-intensity projections (MIP) images of longitudinal PET scans of athymic nude mice bearing HepG2 (right flank) and Huh7 (left flank) tumors injected with 5.6-7.4 MBq of ⁸⁹Zr-Df-YY146 (n = 4; top row). Markedly higher accumulation of the tracer was observed in CD146-expressing HepG2 tumors compared to CD146-negative Huh7 tumors. Mice pre-injected with a blocking dose of YY146 (50 mg/kg) 24 h prior to ⁸⁹Zr-Df-YY146 administration exhibited significantly lower uptake in HepG2 tumors (n = 3; bottom row). Arrows point to the heart (H), liver (L), Huh7 tumor (H7), and HepG2 tumor (H2). B) Region-of-interest (ROI) analysis of the PET images showing the temporal variation of ⁸⁹Zr-Df-YY146's accumulation in HepG2, Huh7, and blocked HepG2 and Huh7 tumors; uptake values are presented as %ID/g ± SD (n = 3 or 4). Significantly higher (P < 0.0001) tracer uptake was observed in non-blocked HepG2 tumors, at all imaging time points. C) Ex vivo biodistribution at 120 h post-injection (p.i.) of ⁸⁹Zr-Df-YY146. Mice were euthanized after the last PET scan and tissues collected, wet-weighed, and counted in a γ-counter. Uptake in the various tissues is givens as %ID/g (mean ± SD; n= 3 or 4). *** P<0.0001.