Journal
JOURNAL OF NUCLEAR MEDICINE
Volume 52, Issue 5, Pages 792-799Publisher
SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.110.086116
Keywords
hypericin; neoplasm; cell damage; near-infrared (NIR); photothermal ablation therapy; positron emission tomography
Funding
- John S. Dunn Foundation
- National Natural Science Foundation of China [30830038]
- Shanghai Leading Academic Discipline Project [S30203]
- European Commission [128-498/111]
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The purpose of this study was to investigate the potential application of small-molecular-weight Cu-64-labeled bis-DOTA-hypericin in the noninvasive assessment of response to photothermal ablation therapy. Methods: Bis-DOTA-hypericin was labeled with Cu-64 with high efficiency (> 95% without purification). Nine mice bearing subcutaneous human mammary BT474 tumors were used. Five mice were injected intratumorally with semiconductor CuS nanoparticles, followed by near-infrared laser irradiation 24 h later (12 W/cm(2) for 3 min), and 4 mice were not treated (control group). All mice were intravenously injected with Cu-64-bis-DOTA-hypericin (24 h after laser treatment in treated mice). Small-animal PET images were acquired at 2, 6, and 24 h after radiotracer injection. All mice were killed immediately after the imaging session for biodistribution and histology study. In vitro cell uptake and surface plasmon resonance studies were performed to validate the small-animal PET results. Results: Cu-64-bis-DOTA-hypericin uptake was significantly higher in the treatment group than in the control group. The percentage injected dose per gram of tissue in the treated and control groups was 1.72 +/- 0.43 and 0.76 +/- 0.19, respectively (P = 0.017), at 24 h after injection. Autoradiography and histology results were consistent with selective uptake of the radiotracer in the necrotic zone of the tumor induced by photothermal ablation therapy. In vitro results showed that treated BT474 cells had a higher uptake of Cu-64-bis-DOTA-hypericin than nontreated cells. Surface plasmon resonance study showed that bis-DOTA-hypericin had higher binding affinity to phosphatidylserine and phosphatidylethanolamine than to phosphatidylcholine. Conclusion: Cu-64-bis-DOTA-hypericin has a potential to image thermal therapy-induced tumor cell damage. The affinity of Cu-64-bis-DOTA-hypericin for injured tissues may be attributed to the breakdown of the cell membrane and exposure of phosphatidylserine or phosphatidylethanolamine to the radiotracer, which binds selectively to these phospholipids.
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