Labelling of human mesenchymal stem cells with indium-111 for SPECT imaging: effect on cell proliferation and differentiation.

PURPOSE: Stem cell therapy seems to be a new treatment option within cardiac diseases to improve myocardial perfusion and function. However, the delivery and traceability of the cells represent a problem. Radioactive labelling with 111In could be a method for tracking mesenchymal stem cells (MSCs). However, 111In could influence the viability and differentiation capacity of MSCs, which would limit its use. Therefore, the aim of this study was to evaluate the influence of 111In labelling in doses relevant for SPECT imaging in humans on the viability and differentiation capacity of human MSCs. METHODS AND RESULTS: Human MSCs isolated from bone marrow were incubated with 111In-tropolone (15-800 Bq/cell). The labelling efficiency was approximately 25% with 30 Bq/cell 111In. The MSC doubling time was 1.04+/-0.1 days and was not influenced by 111In within the range 15-260 Bq/cell. Using 30 Bq 111In/cell it was possible to label MSCs to a level relevant for clinical scintigraphic use. With this dose, 111In had no effect on characteristic surface and intracellular markers of cultured MSCs analysed both by flow cytometry and by real-time polymerase chain reaction. Further, the labelled MSCs differentiated towards endothelial cells and formed vascular structures. CONCLUSION: It is possible to label human MSCs with 111In for scintigraphic tracking of stem cells delivered to the heart in clinical trials without affecting the viability and differentiation capacity of the MSCs. This creates an important tool for the control of stem cell delivery and dose response in clinical cardiovascular trials.

The potential for aromatase inhibition in breast cancer prevention.

Although SERMs are currently being evaluated and are approved for breast cancer prevention in several countries, aromatase inhibitors and inactivators may represent interesting options in this setting. The encouraging results revealing these drugs to be superior to conventional therapy in metastatic breast cancer confirm their therapy efficacy and suggest that they may also have a role in adjuvant therapy and even for breast cancer prevention. Secondly, whereas the bulk of "high-risk" breast cancer patients with confirmed founder mutations in the BRCA1 or BRCA2 genes develop their cancers earlier in life (during the premenopausal period), 75-80% of all breast cancers, in general, develop in postmenopausal women. Thus, in considering prevention of breast cancer in moderate-risk groups, strategies for prevention in postmenopausal women may play an important role. Also, among high-risk patients who have not developed breast cancer by the time of the menopause, aromatase inhibition could be a feasible option. Considering the potential hazards of long-term use of SERMs, switching to an aromatase inhibitor or inactivator in this setting may be beneficial. Finally, the observation that postmenopausal estrogen levels are related to subsequent risk of breast cancer in the general population underlines the potential for estrogen suppression as a preventive strategy. Results from ongoing studies examining the toxicity of aromatase inhibitors and inactivators in postmenopausal women will set the stage for future trials that explore them as preventive treatment options.