Quinic acid derivative KZ-41 exhibits radiomitigating activity in preclinical models of radiation injury.

Acute radiation syndrome is induced when a significant portion of the body receives high-dose, as well as high-dose rate, radiation. We have previously identified a quinic acid-based derivative, KZ-41, that protects from radiation injury. Further preclinical efficacy studies were conducted to determine the radiomitigating activity of KZ-41. C57BL/6 mice received total body irradiation (TBI-LD80/30, ¹³7Cs; ∼2 min) followed by either normal saline or KZ-41 (100 mg/kg sc ∼26 h post-TBI). KZ-41 increased 30-day survival by approximately 45% compared with vehicle controls (P < 0.05). To further investigate the potential radiomodulating mechanisms of KZ-41, we developed a combined radiation and vascular injury model. C57BL/6 mice surgically fixed with dorsal windows for dermal vasculature imaging received either sham or TBI (¹³7Cs; 6 Gray). Postcapillary venule injury was induced (24, 48, 72, and 96 h post-TBI) followed by imaging at 5 min and 24 h to assess clot formation and blood flow. Impairment in flow (P < 0.05) and clot formation (P < 0.05) were observed as early as 48 and 72 h, respectively. Thus, vascular injury 72 h post-TBI was used to evaluate intervention (KZ-41; 100 mg/kg i.p. at 12, 36, and 60 h post-TBI) on radiation-induced changes in both flow and clot formation. KZ-41, although not improving flow, increased clot formation (P < 0.05). Platelet counts were lower in both irradiated groups compared with sham controls (P < 0.05). In summary, KZ-41 exerts radiomitigating activity in lethally irradiated mice. Imaging results suggest KZ-41 exerts radiomitigating activity through mechanisms involving promotion of initial clot formation and vascular flow restoration. The imaging model described herein is useful for further examination of radiation-induced vascular injury repair mechanisms.

In vivo particle tracking and photothermal ablation using plasmon-resonant gold nanostars.

Gold nanostars offer unique plasmon properties that efficiently transduce photon energy into heat for photothermal therapy. Nanostars, with their small core size and multiple long thin branches, exhibit high absorption cross-sections that are tunable in the near-infrared region with relatively low scattering effect, making them efficient photothermal transducers. Here, we demonstrate particle tracking and photothermal ablation both in vitro and in vivo. Using SKBR3 breast cancer cells incubated with bare nanostars, we observed photothermal ablation within 5 minutes of irradiation (980-nm continuous-wave laser, 15 W/cm2). On a mouse injected systemically with PEGylated nanostars for 2 days, extravasation of nanostars was observed and localized photothermal ablation was demonstrated on a dorsal window chamber within 10 minutes of irradiation (785-nm continuous-wave laser, 1.1 W/cm2). These preliminary results of plasmon-enhanced localized hyperthermia are encouraging and have illustrated the potential of gold nanostars as efficient photothermal agents in cancer therapy. FROM THE CLINICAL EDITOR: Gold nanostars are tunable in the near-infrared region with low scattering, thus enable photothermal therapy. Encouraging preliminary results of plasmon-enhanced localized hyperthermia both in vitro and in vivo demonstrate that Au nanostars may be efficient photothermal agents for cancer therapy.

Dual-mode IVUS transducer for image-guided brain therapy: preliminary experiments.

In this study, we investigated the feasibility of using 3.5-Fr intravascular ultrasound (IVUS) catheters for minimally-invasive, image-guided hyperthermia treatment of tumors in the brain. Feasibility was demonstrated by: (1) retro-fitting a commercial 3.5-Fr IVUS catheter with a 5 × 0.5 × 0.22 mm PZT-4 transducer for 9-MHz imaging and (2) testing an identical transducer for therapy potential with 3.3-MHz continuous-wave excitation. The imaging transducer was compared with a 9-Fr, 9-MHz ICE catheter when visualizing the post-mortem ovine brain and was also used to attempt vascular access to an in vivo porcine brain. A net average electrical power input of 700 mW was applied to the therapy transducer, producing a temperature rise of +13.5°C at a depth of 1.5 mm in live brain tumor tissue in the mouse model. These results suggest that it may be feasible to combine the imaging and therapeutic capabilities into a single device as a clinically-viable instrument.