Radiolabeling of progenitor and stem cells with different technetium-99m nanocolloids

Abstract

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Objectives: Due to an increasing use of stem and progenitor cells (PCs) in cardiac phase I/II cell therapy studies, monitoring of transplanted PCs gains clinical interest. So far, the most commonly applied tracers have significant disadvantages such as radiotoxicity and high cellular efflux in case of In-111-oxine, and low cellular uptake in many PC subtypes and a short half-life in case of F-18-FDG. Since most PCs are able to phagocytose nanoparticles such as superparamagnetic iron oxide, as used for MR imaging, the aim of our study was to investigate the possibilities of labeling PCs by incubation with various commercially available radiocolloids.

Methods: For the labeling experiments we used human mesenchymal stem cells (MSCs), human processed lipoaspirate cells (PLACs), and murine embryonic stem cells (MES). 100.000-500.000 cells per well were incubated for 3-9 h with 500 kBq Tc-99m nanocolloids of different sizes and compositions: albumin colloids with a mean diameter of 7-14 nm (Nanocoll) and 205 nm (Senti-Scint) as well as tin colloid with a mean diameter of 140-280 nm (Amerscan tin colloid). After stopping the incubation, cellular retention of Tc-99m tin colloid was measured up to 27 h.

Results: The relative uptake of Nanocoll in MSCs (in % per 1 million cells, n = 3 each) after 3, 6, and 9 h of incubation was 0.5 ± 0.3%, 0.7 ± 0.4%, and 1.1 ± 1.0% (mean ± 1 SD), respectively. The respective values in PLACs were 0.3 ± 0.1%, 0.5 ± 0.2%, and 0.5 ± 0.2%. For Senti-Scint relative uptake was 0.2 ± 0.1%, 0.4 ± 0.4%, and 0.5 ± 0.5% in MSCs, and 0.2 ± 0.1%, 1.8 ± 0.3%, and 0.4 ± 0.3% in PLACs. The highest uptake values were found for tin colloid reaching 2.8 ± 1.5% after 3 h, 5.5 ± 2.5% after 6 h, and 7.1 ± 4.8% after 9 h in MSCs, and 7.7 ± 2.9%, 17.6 ± 3.7%, and 28.0 ± 11.4% in PLACs, respectively. In MES, uptake of tin colloid was 2.8 ± 0.6% after 3 h of incubation. Cellular retention of Tc-99m tin colloid up to 27 h after the end of incubation was higher than 95% in both MSCs and PLACs (n = 5 each) indicating no significant loss out of the cells.

Conclusions: Albumin colloids did not show relevant uptake in progenitor cells irrespectively of their particle size. Inert Tc-99m labeled tin colloid, however, yielded a sufficiently high and incubation time-dependent uptake as well as a stable cellular retention. Radiolabeled tin colloid, therefore, seems to be a promising tracer for stem cell labeling and imaging.