Abstract
1040
Objectives: The aim of this study was to prepare a radiopharmaceutical, 99mTc-hyaluronan, targeting CD44+/CD133+ prostate cancer stem cells. Methods and Results: We successfully isolated CD44+/CD133+ DU-145 cells by fluorescence-activated cell sorting. The microsphere-forming assay showed that this subpopulation possessed self-renewal capability, the key characteristic of cancer stem cells. 99mTc-hyaluronan was prepared by direct labeling method with high radiolabeling yield, which was greater than 98%, and had a high in vitro stability, good affinity, and was specifically taken up by the CD44+/CD133+ DU-145 cells; the uptake (91.8 ± 1.1%) was four-times higher than that in the blocked CD44+/CD133+ DU-145 (22.8 ± 2.8%) and CD44-/CD133- LNCaP cells (18.8 ± 7.4%). At 2 h of administering an injection of 99mTc-hyaluronan, the radioactivity uptake by tumors reached the highest level in nude mice bearing CD44+/CD133+ DU-145 tumors (4.91 ± 0.20%ID/g), which was significantly higher than that in nude mice bearing CD44-/CD133- LNCaP tumors at the same time point (0.98 ± 0.13%ID/g). Moreover, SPECT/CT imaging also showed clear uptake of 99mTc-hyaluronan by the CD44+/CD133+ DU-145 tumors at 30 min of the injection.
Conclusions: These results demonstrate that 99mTc-hyaluronan is an ideal molecular imaging probe for prostate cancer stem cells, and lay the foundation for targeted radiotherapy of prostate cancer.