Biodistribution studies of ⁸⁹Zr-Labeled stem cell-derived exosomes using PET imaging

In this study, exosomes isolated from embryonic stem cells were labeled with ⁸⁹Zr-DFO. The resulting ⁸⁹Zr-DFO-exo were subsequently injected into mice via subcutaneous, intraperitoneal, intravenous routes. At various time points post injection, PET/CT imaging was conducted to monitor the in vivo biodistribution profiles. For subcutaneous injection, PET quantification showed significant tracer accumulation at the injection sites up to 13 days post-injection, with % ID/g values of 40 ± 5, 37 ± 4, and 33 ± 5 at days 1, 7, and 13, respectively. Less than 20 % of the injected tracer entered the bloodstream, with kidney clearance showing % ID/g values of 5 ± 2, 3 ± 2, and 2 ± 1 % at days 1, 7, and 13 post-injection. In contrast, the intraperitoneal-injected mice primarily exhibited tracer accumulation in the stomach and spleen, with % ID/g as follows: stomach-11 ± 3,10 ± 3, and 8 ± 3; spleen -10 ± 3, 9 ± 3, and 7 ± 2 at days 1, 7, and 13 pi (n = 3). In intravenous injection group, PET revealed that radioactivity was primarily concentrated in the lung, liver, and spleen at all time points, with the following % ID/g values: lungs-10 ± 4, 6 ± 3, and 8 ± 4; liver-7±3, 5 ± 3, and 4.5 ± 3.5; spleen-7±4, 8 ± 3, and 6 ± 4 at 1, 24, and 48 h pi, respectively (n = 3). For all three groups with different injection routes, minimal uptake was detected in the bone during all study durations, indicating high in vivo stability of ⁸⁹Zr-DFO-exo. The ex vivo biodistribution data were consistent with PET. PET imaging proved to be an invaluable tool for tracking the biodistribution of ⁸⁹Zr-DFO-exo over time.