Cytotoxicity of 111In-oxine on mesenchymal stem cells: a time-dependent adverse effect

Radioactive labeling with indium (In) tracers has been among the most widely used methods for tracking stem cells. As the first experiment on human stem cells, we designed a study to continuously follow the influence of In labeling on stem cell viability during the 2-week period of postlabeling.

After culturing mesenchymal stem cells (MSCs), we divided the cells into six samples, each of which contained 1x10 MSCs. The first sample was considered as the control. The remaining five samples (samples 2-6) were labeled with the following doses of In-oxine, respectively: 0.76, 1.64, 3.48, 5.33, and 7.16 MBq/10 MSCs. To evaluate the effects of In-oxine labeling on cellular viability and count, all samples were examined immediately after labeling (2 h) as well as 24, 48 h, and 5, 7, and 14 days postlabeling.

No statistically significant relationship was found between labeling efficiency and administered dose. Associations between the specific activity and radiotracer dosage was significant (P=0.001, r=0.9). In addition, a negative correlation was noted between radiotracer dosage and viability during the 2-week period of follow-up.

Cytotoxic effects of In on human stem cells is a time-dependent phenomenon and hence, assessment of the stem cell viability immediately after labeling (which is frequently made in clinical trials) is unable to detect adverse effects of this radiopharmaceutical on the integrity of stem cells. Even low doses of In-oxine are accompanied by significant cell loss in a 2-week period. Although it has been confirmed that nuclear medicine techniques are the most sensitive methods for stem cell tracking, we recommend that the application of this tracking technique should be treated with great reserve, and if necessary, as little of In-oxine as possible should be added to the cells (or only a limited portion of the cells should be labeled) to minimize cell death.