Radiation-damaged nanodiamonds (NDs) are ideal optical contrast agents for photoacoustic (PA) imaging in biological tissues due to their good biocompatibility and high optical absorbance in the near-infrared (NIR) range. Acid treated NDs are oxidized to form carboxyl groups on the surface, functionalized with polyethylene glycol (PEG) and human epidermal growth factor receptor 2 (HER2) targeting ligand for breast cancer tumor imaging. Because of the specific binding of the ligand conjugated NDs to the HER2-overexpressing murine breast cancer cells (4T1.2 neu), the tumor tissues are significantly delineated from the surrounding normal tissue at wavelength of 820 nm under the PA imaging modality. Moreover, HER2 targeted NDs (HER2-PEG-NDs) result in higher accumulation in HER2 positive breast tumors as compared to non-targeted NDs after intravenous injection (i.v.). Longer retention time of HER-PEG-NDs is observed in HER2 overexpressing tumor model than that in negative tumor model (4T1.2). This demonstrates that targeting moiety conjugated NDs have great potential for the sensitive detection of cancer tumors and provide an attractive delivery strategy for anti-cancer drugs.
Radiation-damaged nanodiamonds (DNDs) are potentially ideal optical contrast agents for photoacoustic (PA) imaging in biological tissues due to their low toxicity and high optical absorbance. PA imaging contrast agents have been limited to quantum dots and gold particles, since most existing carbon-based nanoparticles, including fluorescent nanodiamonds, do not have sufficient optical absorption in the near-infrared (NIR) range. A new DND by He + ion beam irradiation with very high NIR absorption was synthesized. These DNDs produced a 71-fold higher PA signal on a molar basis than similarly dimensioned gold nanorods, and 7.1 fmol of DNDs injected into rodents could be clearly imaged 3 mm below the skin surface with PA signal enhancement of 567% using an 820-nm laser wavelength.
Anti-cancer drugs typically exert their pharmacological effect on tumors by inducing apoptosis, or programmed cell
death, within the cancer cells, with PCD occurring as soon as 4 hours after treatment. Detection of apoptosis in patients
could decisively report a response to treatment days or even weeks before MRI, CAT, and ultrasound indicate
morphological changes in the tumor. Here we developed a novel
near-infrared dye based imaging probe to directly detect
apoptosis with high specificity in cancer cells by utilizing a
non-invasive photoacoustic imaging technique. Nude mice
bearing head and neck tumors received cisplatin chemotherapy were imaged by PAI after tail vein injection of the
contrast agent. In vivo PAI indicated a strong apoptotic response to chemotherapy on the peripheral margins of tumors,
whereas untreated controls showed no contrast enhancement by PAI. The apoptotic status of the mouse tumor tissue was
verified by immunohistochemical techniques staining for cleaved caspase-3 p11 subunit. The results demonstrated the
potential of this imaging probe to guide the evaluation of chemotherapy treatment.
Anti-cancer drugs typically exert their pharmacological effect on tumors by inducing apoptosis, or programmed cell death, within the cancer cells. However, no tools exist in the clinic for detecting apoptosis in real time. Microscopic examination of surgical biopsies and secondary responses, such as morphological changes, are used to verify efficacy of a treatment. Here, we developed a novel near-infrared dye-based imaging probe to directly detect apoptosis with high specificity in cancer cells by utilizing a noninvasive photoacoustic imaging (PAI) technique. Nude mice bearing head and neck tumors received cisplatin chemotherapy (10 mg/kg) and were imaged by PAI after tail vein injection of the contrast agent. In vivo PAI indicated a strong apoptotic response to chemotherapy on the peripheral margins of tumors, whereas untreated controls showed no contrast enhancement by PAI. The apoptotic status of the mouse tumor tissue was verified by immunohistochemical techniques staining for cleaved caspase-3 p11 subunit. The results demonstrated the potential of this imaging probe to guide the evaluation of chemotherapy treatment.
In this study, we applied an integrated photoacoustic imaging (PAI) and high intensity focused ultrasound (HIFU)
system to noninvasively monitor the thermal damage due to HIFU ablation in vivo. A single-element, spherically focused
ultrasonic transducer, with a central frequency of 5MHz, was used to generate a HIFU area in soft tissue. Photoacoustic
signals were detected by the same ultrasonic transducer before and after HIFU treatments using different wavelengths.
The feasibility of combined contrast imaging and treatment of solid tumor in vivo by the integrated PAI and HIFU
system was also studied. Gold nanorods were used to enhance PAI during the imaging of a CT26 tumor, which was
subcutaneously inoculated on the hip of a BALB/c mouse. Subsequently, the CT26 tumor was ablated by HIFU with the
guidance of photoacoustic images. Our results suggested that the tumor was clearly visible on photoacoustic images
after the injection of gold nanorods and was ablated by HIFU. In conclusion, PAI may potentially be used for
monitoring HIFU thermal lesions with possible diagnosis and treatment of solid tumors.
Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.
We have developed an integrated photoacoustic imaging (PAI) and high-intensity focused ultrasound (HIFU) system for solid tumor treatments. A single-element, spherically focused ultrasonic transducer, with a central frequency of 5 MHz, was used to induce HIFU lesions in soft tissue. The same ultrasonic transducer was also used as a detector during PAI to guide HIFU ablation. The use of same transducer for PAI and HIFU can reduce the requirement on acoustic windows during the imaging-guided therapy, as well as ensuring the correct alignment between the therapeutic beam and the planned treatment volume. During an experiment, targeted soft tissue was first imaged by PAI. The resulted image was used to plan the subsequent HIFU ablation. After the HIFU ablation, targeted soft tissue was imaged again by PAI to evaluate the effectiveness of treatments. Good contrast was obtained between photoacoustic images before and after HIFU ablation. In conclusion, our results demonstrated that PAI technology may potentially be integrated with HIFU ablation for image-guided therapy.
We have developed an integrated photoacoustic imaging (PAI) and high intensity focused ultrasound (HIFU) system for
solid tumor treatment. A single-element, spherically focused ultrasonic transducer, with a central frequency of 5MHz,
was used to generate a HIFU field in soft tissue. The same ultrasonic transducer was also used as a detector during
photoacoustic imaging before and after HIFU treatments. During each experiment, targeted soft tissue was first imaged
by PAI. The resulted image was used for the planning of subsequent HIFU treatment. After HIFU treatment, the sample
was imaged again by PAI to evaluate the treatment result. Good contrast was obtained between photoacoustic images
before and after HIFU treatment. It is concluded that PA imaging technology may potentially be combined with HIFU
treatment for imaging-guided therapy.
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