Therapeutic efficacy of an alpha-particle emitter labeled anti-GD2 humanized antibody against osteosarcoma-a proof of concept study.

PURPOSE: Current treatments for osteosarcoma (OS) have a poor prognosis, particularly for patients with metastasis and recurrence, underscoring an urgent need for new targeted therapies to improve survival. Targeted alpha-particle therapy selectively delivers cytotoxic payloads to tumors with radiolabeled molecules that recognize tumor-associated antigens. We have recently demonstrated the potential of an FDA approved, humanized anti-GD2 antibody, hu3F8, as a targeted delivery vector for radiopharmaceutical imaging of OS. The current study aims to advance this system for alpha-particle therapy of OS. METHODS: The hu3F8 antibody was radiolabeled with actinium-225, and the safety and therapeutic efficacy of the [225Ac]Ac-DOTA-hu3F8 were evaluated in both orthotopic murine xenografts of OS and spontaneously occurring OS in canines. RESULTS: Significant antitumor activity was proven in both cases, leading to improved overall survival. In the murine xenograft's case, tumor growth was delayed by 16-18 days compared to the untreated cohort as demonstrated by bioluminescence imaging. The results were further validated with magnetic resonance imaging at 33 days after treatment, and microcomputed tomography and planar microradiography post-mortem. Histological evaluations revealed radiation-induced renal toxicity, manifested as epithelial cell karyomegaly and suggestive polyploidy in the kidneys, suggesting rapid recovery of renal function after radiation damage. Treatment of the two canine patients delayed the progression of metastatic spread, with an overall survival time of 211 and 437 days and survival beyond documented metastasis of 111 and 84 days, respectively. CONCLUSION: This study highlights the potential of hu3F8-based alpha-particle therapy as a promising treatment strategy for OS.

Thermal Characterization and Preclinical Feasibility Verification of an Accessible, Carbon Dioxide-Based Cryotherapy System.

To investigate the potential of an affordable cryotherapy device for the accessible treatment of breast cancer, the performance of a novel carbon dioxide-based device was evaluated through both benchtop testing and an in vivo canine model. This novel device was quantitatively compared to a commercial device that utilizes argon gas as the cryogen. The thermal behavior of each device was characterized through calorimetry and by measuring the temperature profiles of iceballs generated in tissue phantoms. A 45 min treatment in a tissue phantom from the carbon dioxide device produced a 1.67 ± 0.06 cm diameter lethal isotherm that was equivalent to a 7 min treatment from the commercial argon-based device, which produced a 1.53 ± 0.15 cm diameter lethal isotherm. An in vivo treatment was performed with the carbon dioxide-based device in one spontaneously occurring canine mammary mass with two standard 10 min freezes. Following cryotherapy, this mass was surgically resected and analyzed for necrosis margins via histopathology. The histopathology margin of necrosis from the in vivo treatment with the carbon dioxide device at 14 days post-cryoablation was 1.57 cm. While carbon dioxide gas has historically been considered an impractical cryogen due to its low working pressure and high boiling point, this study shows that carbon dioxide-based cryotherapy may be equivalent to conventional argon-based cryotherapy in size of the ablation zone in a standard treatment time. The feasibility of the carbon dioxide device demonstrated in this study is an important step towards bringing accessible breast cancer treatment to women in low-resource settings.

Técnicas no invasivas de imagen cardiovascular en investigación básica: aplicación en la terapia celular / Noninvasive cardiovascular imaging techniques for basic science research: application to cellular therapeutics

La terapia celular continúa siendo un área muy activa en el campo de la investigación básica, con resultados iniciales prometedores en el tratamiento de las enfermedades cardiovasculares. Sin embargo, aún existen muchos factores desconocidos en la terapia celular, entre los que se incluyen el mecanismo de acción, los tipos de células que resultan más útiles, las estrategias de administración más eficaces, así como su seguridad. La obtención de imágenes con métodos no invasivos permite utilizar una gran variedad de herramientas para valorar cuantitativamente muchos de estos factores desconocidos. En este artículo nos centramos en la ecocardiografía, la resonancia magnética, la tomografía computarizada, la tomografía por emisión de positrones y la tomografía por emisión de fotón único en el contexto de la terapia celular, para explicar la forma en que estas modalidades de imagen se están utilizando para dar respuesta a muchas de esas cuestiones (AU)

Cell therapy continues to be an active area of basic science research with early promise in the treatment of cardiovascular diseases. However, there are many unknowns including the mechanisms by which they work, the most useful cell types, the most efficient delivery strategies, and their safety. Noninvasive imaging provides a wide array of tools to quantitatively address many of these unknowns. This article reviews echocardiography, magnetic resonance imaging, computed tomography, positron emission tomography and single photon emission tomography in the context of imaging cellular therapeutics to demonstrate how these modalities are being used to answer some of these questions (AU)