Interstitial Photothermal Therapy Research Articles

Interstitial Photothermal Therapy Generates Durable Treatment Responses in Neuroblastoma.

Photothermal therapy (PTT) represents a promising modality for tumor control typically using infrared light-responsive nanoparticles illuminated by a wavelength-matched external laser. However, due to the constraints of light penetration, PTT is generally restricted to superficially accessible tumors. With the goal of extending the benefits of PTT to all tumor settings, interstitial PTT (I-PTT) is evaluated by the photothermal activation of intratumorally administered Prussian blue nanoparticles witha laser fiber positioned interstitially within the tumor. This interstitial fiber, which is fitted with a terminal diffuser, distributes light within the tumor microenvironment from the "inside-out" as compared to from the "outside-in" traditionally observed during superficially administered PTT (S-PTT). I-PTT improves the heating efficiency and heat distribution within a target treatment area compared to S-PTT. Additionally, I-PTT generates increased cytotoxicity and thermal damage at equivalent thermal doses, and elicits immunogenic cell death at lower thermal doses in targeted neuroblastoma tumor cells compared to S-PTT. In vivo, I-PTT induces significantly higher long-term tumor regression, lower rates of tumor recurrence, and improved long-term survival in multiple syngeneic murine models of neuroblastoma. This study highlights the significantly enhanced therapeutic benefit of I-PTT compared to traditional S-PTT as a promising treatment modality for solid tumors.

Multifunctional magnetic-gold nanoparticles for efficient combined targeted drug delivery and interstitial photothermal therapy

Abundant efforts have recently been made to design potent theranostic nanoparticles, which combine diagnostic and therapeutic agents, for the effective treatment of cancer. In this study, we developed multifunctional magnetic gold nanoparticles (MGNPs) that are able to (i) selectively deliver the drug to the tumor site in a controlled-release manner, either passively or by using magnetic targeting; (ii) induce photothermal therapy by producing heat by near-infrared (NIR) laser absorption; and (iii) serve as contrast agents for magnetic resonance imaging (MRI) (imaging-guided therapy). The prepared MGNPs were characterized by different physical techniques. They were then coated and conjugated with polyethylene glycol (PEG) and doxorubicin (DOX) to form MGNP-DOX conjugates. The high efficacy of MGNP-DOX for combined chemo-photothermal therapy was observed both in vitro and in vivo. The effectiveness of MGNP-DOX as theranostic nanoparticles was confirmed by histopathological examination and immunohistochemical studies. Moreover, MGNP-DOX showed good potential as MRI contrast agents for guided chemo-photothermal synergistic therapy.

Shape-based reconstruction for transrectal diffuse optical tomography monitoring of photothermal focal therapy of prostate cancer: simulation studies.

We develop and demonstrate a simple shape-based approach for diffuse optical tomographic reconstruction of coagulative lesions generated during interstitial photothermal therapy (PTT) of the prostate. The shape-based reconstruction assumes a simple ellipsoid shape, matching the general dimensions of a cylindrical diffusing fiber used for light delivery in current clinical studies of PTT in focal prostate cancer. The specific requirement is to accurately define the border between the photothermal lesion and native tissue as the photothermal lesion grows, with an accuracy of ? 1 ?? mm , so treatment can be terminated before there is damage to the rectal wall. To demonstrate the feasibility of the shape-based diffuse optical tomography reconstruction, simulated data were generated based on forward calculations in known geometries that include the prostate, rectum, and lesions of varying dimensions. The only source of optical contrast between the lesion and prostate was increased scattering in the lesion, as is typically observed with coagulation. With noise added to these forward calculations, lesion dimensions were reconstructed using the shape-based method. This approach for reconstruction is shown to be feasible and sufficiently accurate for lesions that are within 4 mm from the rectal wall. The method was also robust for irregularly shaped lesions.

Diffuse optical tomography to monitor the photocoagulation front during interstitial photothermal therapy: Numerical simulations and measurements in tissue-simulating phantoms

AbstractNear-infrared interstitial photothermal therapy (PTT) is currently undergoing clinical trials as an alternative to watchful waiting or radical treatments in patients with low/intermediate-risk focal prostate cancer. Currently, magnetic resonance imaging (MRI)-based thermography is used to monitor thermal energy delivery and determine indirectly the completeness of the target tumor destruction while avoiding damage to adjacent normal tissues, particularly the rectal wall. As an alternative, transrectal diffuse optical tomography (TRDOT) is being developed to image directly the photocoagulation boundary based on the changes in tissue optical properties, particularly scattering. An established diffusion-theory finite-element software platform was used to perform forward simulations to determine the sensitivity of changes in the optical signal resulting from a growing coagulated lesion with optical scattering contrast, for varying light source-detector separations in both longitudinal and transverse imaging geometries. The simulations were validated experimentally in tissue-simulating phantoms using an existing continuous-wave TRDOT system, in a configuration that is representative of one potential intended clinical use. This provides critical guidance for the optimum design of the transrectal applicator probe, in terms of achieving maximum sensitivity to the presence of the coagulation boundary and, consequently, the highest accuracy in determining the boundary location relative to the rectal wall.

Optimization in interstitial plasmonic photothermal therapy for treatment planning

Gold nanorods have the potential to enhance the treatment efficacy of interstitial photothermal therapy. In order to enhance both the potential efficiency and the safety of such procedures, treatment planning on laser power density, nanoparticle concentration, and exposure time has turned out to be useful in predicting the thermal damage and optimizing treatment outcome. To the best of our knowledge, there is no previous report on the optimization of interstitial plasmonic photothermal therapy (PPTT) for all these free parameters simultaneously. The authors propose to develop a suitable optimization algorithm for interstitial PPTT to optimize these parameters and achieve complete damage to spherical tumors of different sizes with a damage margin width of 1 mm from the tumor boundary embedded deep inside a normal tissue model. In a numerical tissue model, the standard Pennes bioheat equation and the first-order thermal-chemical rate equation were used to model the temperature and thermal damage distributions, respectively, in spherical tumors that were embedded deep inside a normal tissue and incubated with nanorods. The concentration of nanorods in the normal tissue was set to be about one quarter of that in the tumor. Thermal damage due to varying concentrations of nanorods, laser power density, and exposure time was computed for a series of tumor radii including 2, 3, 4, and 5 mm. An optimization algorithm was developed to determine the optimum laser power density, nanorod concentration, and exposure time for the treatment of such spherical tumors. In this algorithm, a novel objective function was created to enable the optimization of multiple key parameters, including nanoparticle concentration, power density, and exposure time, simultaneously to achieve not only the complete thermal damage to the entire tumor but also the collateral damage to the surrounding normal tissue with a margin width of 1 mm from the tumor boundary. Different weights were assigned sequentially to each free parameter according to the relative importance of the parameters. A thermal damage value of one calculated by Arrhenius damage law, which is more accurate than a threshold temperature typically used for characterizing thermal damage, was used to indicate effective treatment. The simulation results show that there is a steady increase in the overall temperature as the nanorod concentration increases; however, the uniformity of the temperature distribution changes significantly which in turn affects the thermal damage. Optimization results show that any slight decrease in one free parameter can be compensated by the increase in other free parameters, in which the complete thermal damage of the tumor and the collateral damage to normal tissue with a margin width of 1 mm can be always achieved. This implies the importance of optimization in interstitial PPTT. The proposed method can optimize laser power density, nanoparticle concentration, and exposure time simultaneously with different weights in interstitial PPTT planning for deep seated tumors. It provides flexibility for a clinician to make appropriate planning for individual patients according to their special needs.

A neodymium:YAG fiber delivery system for interstitial photothermal therapy.

We describe here a highly durable 600-mu optical fiber with a 20-mm frosted distal tip protected by a smooth transparent cover that is capable of remaining in contact with tissue for prolonged periods. When used with a neodymium:YAG (Nd:YAG) laser, the active fiber surface diffuses optical radiation in a radial pattern, delivering up to 40 W power, and thus providing consistent and uniform interstitial photothermal therapy. Preliminary animal studies have demonstrated the feasibility of using these fibers to treat a variety of soft-tissue tumors, including benign prostatic hyperplasia.