Intratumoral injections often lack visibility, leading to unpredictable outcomes such as incomplete tumor coverage, off-target drug delivery and systemic toxicities. This study investigated an ultrasound (US) and x-ray imageable thermosensitive hydrogel based on poloxamer 407 (POL) percutaneously delivered in a healthy swine model. The primary objective was to assess the 2D and 3D distribution of the hydrogel within tissue across three different needle devices and injection sites: liver, kidney, and intercostal muscle region.
View Article and Find Full Text PDFPurpose: The aim of this study was to assess the feasibility of quantifying morphologic changes in tumors during immunotherapy, as a reflection of response or survival.
Methods And Materials: A retrospective single-center analysis was performed in patients with unresectable liver cancer previously enrolled in clinical trials combining immunotherapy (tremelimumab ± durvalumab) and locoregional treatment (either ablation or transarterial chemoembolization). Conventional response (RECIST 1.
Intratumoral injections often lack visibility, leading to unpredictable outcomes such as incomplete tumor coverage, off-target drug delivery and systemic toxicities. This study investigated an ultrasound (US) and x-ray imageable thermosensitive hydrogel based on poloxamer 407 (POL) percutaneously delivered in a healthy swine model. The primary objective was to assess the 2D and 3D distribution of the hydrogel within tissue across three different needle devices and injection sites: liver, kidney, and intercostal muscle region.
View Article and Find Full Text PDFTransarterial chemoembolization (TACE) is an image-guided minimally invasive treatment for liver cancer which involves delivery of chemotherapy and embolic material into tumor-supplying arteries to block blood flow to a liver tumor and to deliver chemotherapy directly to the tumor. However, the released drug diffuses only less than a millimeter away from the beads. To enhance the efficacy of TACE, the development of microbubbles electrostatically bound to the surface of drug-eluting beads loaded with different amounts of doxorubicin (0-37.
View Article and Find Full Text PDFIntratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs).
View Article and Find Full Text PDFLiver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution.
View Article and Find Full Text PDFLiver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution.
View Article and Find Full Text PDFJ Hepatocell Carcinoma
November 2023
Objectives: Local and systemic immune responses evoked by locoregional therapies such as cryoablation are incompletely understood. The aim of this study was to characterize cryoablation-related immune response and the capacity of immune drugs to augment immunity upon cryoablation for the treatment of hepatocellular carcinoma (HCC) using a woodchuck hepatocellular carcinoma model.
Materials And Methods: Twelve woodchucks chronically infected with woodchuck hepatitis virus and with hepatocellular carcinoma underwent imaging with contrast-enhanced CT.
Although systemic immunotherapy has achieved durable responses and improved survival for certain patients and cancer types, low response rates and immune system-related systemic toxicities limit its overall impact. Intratumoral (intralesional) delivery of immunotherapy is a promising technique to combat mechanisms of tumor immune suppression within the tumor microenvironment and reduce systemic drug exposure and associated side effects. However, intratumoral injections are prone to variable tumor drug distribution and leakage into surrounding tissues, which can compromise efficacy and contribute to toxicity.
View Article and Find Full Text PDFThis review highlights opportunities to develop accessible ablative therapies to reduce the cancer burden in LMICs.
View Article and Find Full Text PDFWe characterized cryoablation as a mode of clinical intervention in adult woodchucks with hepatocellular carcinoma (HCC). Woodchucks ( = 4) were infected with woodchuck hepatitis virus at birth and developed LI-RADS-5 hypervascular HCC. At 21 mo of age, they underwent ultrasound (US), contrast-enhanced CT (CECT) imaging, and US-guided subtotal cryoablation (IcePearl 2.
View Article and Find Full Text PDFThe immune response to radiofrequency ablation (RFA) and cryoablation (CRA) was characterized and compared in a colon cancer mouse model. All studies were conducted under a research protocol approved by the National Institutes of Health, Clinical Center, Animal Care and Use Committee. BALB/cJ mice were inoculated with CT26 cells, and randomized to RFA, CRA, or sham treatment.
View Article and Find Full Text PDFObjectives: The aims of this study were to develop a model to estimate drug dose delivered to tumors after transarterial chemoembolization (TACE) with radiopaque drug-eluting beads (DEBs) based on DEB density on cone-beam computed tomography (CT) and to evaluate drug penetration into tissue in a woodchuck hepatoma model.
Materials And Methods: Transarterial chemoembolization was performed in woodchucks with hepatocellular carcinoma (N = 5) using DEBs (70-150 μm, LC Bead LUMI) loaded with doxorubicin. Livers were resected 45 minutes after embolization, immediately frozen, and cut using liver-specific, 3D-printed sectioning molds.
Cancer immunotherapy has yet to reach its full potential due in part to limited response rates and side effects inherent to systemic delivery of immune-modulating drugs. Local administration of immunotherapy using drug-eluting embolic (DEE) microspheres as drug delivery vehicles for direct infusion into tumor-feeding arteries might increase and prolong tumor drug concentrations and reduce systemic drug exposure, potentially improving the risk-to-benefit ratio of these agents. The purpose of this study was to evaluate the ability of four immune modulators affecting two different immune pathways to potentiate replication of immune cells from a woodchuck model of hepatocellular carcinoma.
View Article and Find Full Text PDFPurpose: To characterize the hepatic and abdominal angiographic anatomy of woodchucks and vascular changes associated with hepatocellular carcinoma (HCC).
Materials And Methods: Twenty-nine woodchucks (23 with viral-associated HCC, 6 without) underwent multiphasic computed tomography (CT). Fourteen woodchucks (8 with HCC) also underwent diagnostic angiography.
Cardiovasc Intervent Radiol
September 2021
Purpose: To evaluate an integrated liver biopsy platform that combined CT image fusion, electromagnetic (EM) tracking, and optical molecular imaging (OMI) of indocyanine green (ICG) to target hepatocellular carcinoma (HCC) lesions and a point-of-care (POC) OMI to assess biopsy cores, all based on tumor retention of ICG compared to normal liver, in phantom and animal model.
Material: A custom CT image fusion and EM-tracked guidance platform was modified to integrate the measurement of ICG fluorescence intensity signals in targeted liver tissue with an OMI stylet or a POC OMI system. Accuracy was evaluated in phantom and a woodchuck with HCC, 1 day after administration of ICG.
Introduction: Drug-eluting embolic (DEE) microspheres, or drug-eluting beads (DEB), delivered by transarterial chemoembolization (TACE) serve as a therapeutic embolic to stop blood flow to tumors and a drug delivery vehicle. New combinations of drugs and DEE microspheres may exploit the potential synergy between mechanisms of drug activity and local tissue responses generated by TACE to enhance the efficacy of this mainstay therapy.
Areas Covered: This review provides an overview of key drug delivery concepts related to DEE microspheres with a focus on recent technological developments and promising emerging clinical applications as well as speculation into the future.
Background: Teratomas are germ cell neoplasms composed of a wide variety of tissues. In the woodchuck, only one testicular teratoma has been described in the literature. The objective of this report was to describe the radiologic and pathologic findings in a female woodchuck (Marmota monax) with an ovarian teratoma consisting of mature tissues originating from all three germ layers.
View Article and Find Full Text PDFPurpose: To evaluate the spatial registration and correlation of liver and tumor histopathology sections with corresponding in vivo CT and MRI using 3D, liver-specific cutting molds in a woodchuck (Marmota monax) hepatic tumor model.
Methods: Five woodchucks chronically infected with woodchuck hepatitis virus following inoculation at birth and with confirmed hepatic tumors were imaged by contrast enhanced CT or MRI. Virtual 3D liver or tumor models were generated by segmentation of in vivo CT or MR imaging.
Purpose: To assess the feasibility of transarterial chemoembolization with drug-eluting embolic (DEE) microspheres in a woodchuck model of hepatocellular carcinoma (HCC).
Materials And Methods: Nine woodchucks were studied: 4 normal animals and 5 animals infected with woodchuck hepatitis virus in which HCC had developed. Three animals with HCC underwent multidetector CT.