JNM: PET can image therapy-induced tumor cell damage

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64Cu-bis-DOTA-hypericin has potential to image thermal therapy-induced tumor cell damage, according to a study in this month’s Journal of Nuclear Medicine.

The purpose of this study was to investigate the potential application of small-molecular-weight 64Cu-labeled bis-DOTA-hypericin in the noninvasive assessment of response to photothermal ablation therapy. Bis-DOTA-hypericin was labeled with 64Cu with high efficiency (greater than 95 percent without purification), according to the study authors.

Shaoli Song, MD, of the department of experimental diagnostic imaging at the University of Texas M.D. Anderson Cancer Center in Houston, and colleagues used nine mice bearing subcutaneous human mammary BT474 tumors. They injected five mice intratumorally with semiconductor CuS nanoparticles, followed by near-infrared laser irradiation 24 hours later (12 W/cm2 for three minutes), and four mice were not treated (control group). They also intravenously injected all mice with 64Cu-bis-DOTA-hypericin (24 hours after laser treatment in treated mice).

The researchers acquired small-animal PET images at two, six and 24 hours 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.

64Cu-bis-DOTA-hypericin uptake was significantly higher in the treatment group than in the control group, the study authors reported. The percentage injected dose per gram of tissue in the treated and control groups was 1.72 and 0.76, respectively, at 24 hours after injection.

Also, they noted that the 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 64Cu-bis-DOTA-hypericin than non-treated cells. Surface plasmon resonance study showed that bis-DOTA-hypericin had higher binding affinity to phosphatidylserine and phosphatidylethanolamine than to phosphatidylcholine.

Song and colleagues concluded affinity of 64Cu-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.

“The ability to monitor response to CuS nanoparticle–mediated PTA should provide the opportunity for the noninvasive assessment of response to photothermal ablation and other thermal ablation techniques,” the study authors wrote.