Purpose:To determine if pulsed-high intensity focused ultrasound (HIFU) could effectively serve as a source of hyperthermia with thermosensitive liposomes to enhance delivery and efficacy of doxorubicin in tumors. Experimental Design: Comparisons in vitro and in vivo were carried out between nont hermosensitive liposomes (NTSL) and low temperature^sensitive liposomes (LTSL). Liposomes were incubated in vitro over a range of temperatures and durations, and the amount of doxorubicin released was measured. For in vivo experiments, liposomes and free doxorubicin were injected i.v. in mice followed by pulsed-HIFU exposures in s.c. murine adenocarcinoma tumors at 0 and 24 h after administration. Combinations of the exposures and drug formulations were evaluated for doxorubicin concentration and growth inhibition in the tumors. Results: In vitro incubations simulating the pulsed-HIFU thermal dose (42jC for 2 min) triggered release of 50% of doxorubicin from the LTSLs; however, no detectable release from the NTSLs was observed. Similarly, in vivo experiments showed that pulsed-HIFU exposures combined with the LTSLs resulted in more rapid delivery of doxorubicin as well as significantly higher i.t. concentration when compared with LTSLs alone or NTSLs, with or without exposures. Combining the exposures with the LTSLs also significantly reduced tumor growth compared with all other groups. Conclusions: Combining low-temperature heat-sensitive liposomes with noninvasive and nondestructive pulsed-HIFU exposures enhanced the delivery of doxorubicin and, consequently, its antitumor effects. This combination therapy could potentially produce viable clinical strategies for improved targeting and delivery of drugs for treatment of cancer and other diseases.The dose of drug required to achieve clinically effective cytotoxicity in tumors often causes severe damage to actively propagating nonmalignant cells, resulting in a variety of undesirable side effects (1). Abnormal and heterogeneous distribution of inefficient vasculature (2), high interstitial fluid pressures (3), and fibrillar collagen in the extracellular matrix (4) are some of the barriers that further complicate effective and uniform drug delivery to tumors. Novel paradigms to overcome these barriers with new drug and device combinations may present fertile ground for continued research.Employing drug delivery strategies, such as liposomal encapsulation, can optimize and enhance the delivery of different agents with lower systemic toxicity and better drug cell internalization compared with free drug (5). A smaller volume of distribution and prolonged clearance time may also be achieved by incorporating lipid-conjugated polyethylene glycol into the liposomal membrane. This polyethylene glycolylation provides a protective barrier against interactions with plasma proteins and the reticuloendothelial system, allowing for enhanced accumulation of the chemotherapeutic agent into tumors (6). Polyethylene glycolylated liposomes containing doxorubicin, or Doxil, have bee...

Purpose: To investigate whether combining pulsed high-intensity focused ultrasound (HIFU) with the chemotherapeutic drug bortezomib could improve antitumor activity against murine squamous cell carcinoma (SCC) tumors. Materials and Methods: All experiments were conducted with animal care and use committee approval. Murine SCC cells were implanted subcutaneously in C3H mice. When tumors reached 100 mm3, mice were randomized to one of three groups for twice weekly intraperitoneal injections of 1.5 mg of bortezomib per kilogram of body weight, a proteasome inhibitor (n = 10); 1.0 mg/kg bortezomib (n = 11); or a control vehicle (n = 12). Within each group, half of the mice received pulsed HIFU exposure to their tumors immediately prior to each injection. The time for tumors to reach 650 mm3 was compared among groups. Additional tumors were stained with terminal deoxynucledotidyl transferase-mediated dUTP nick end labeling and CD31 to assess apoptotic index and blood vessel density, respectively. Results: Tumors in the control group, pulsed HIFU and control group, and 1.0 mg/kg of bortezomib alone group reached the size end point in 5.2 days ± 0.8 (standard deviation), 5.3 days ± 0.8, and 5.6 days ± 1.1, respectively. However, pulsed HIFU and 1.0 mg/kg bortezomib increased the time to end point to 9.8 days ± 2.9 (P < .02), not significantly different from the 8.8 days ± 2.1 in tumors treated with 1.5 mg/kg bortezomib alone (P > .05). Combination therapy was also associated with a significantly higher apoptotic index (P < .05). Conclusion: Treatment of tumors with pulsed HIFU lowered the threshold level for efficacy of bortezomib, resulting in significant tumor cytotoxicity and growth inhibition at lower dose levels.

In patients with renal impairment, the incremental benefits from administration of contrast media for imaging studies need to be carefully assessed relative to the potential increased risks of worsening renal dysfunction and systemic adverse effects. This review provides an overview of risk and benefits of iodinated and gadolinium-based contrast agents; examines their relationships to contrast-induced nephropathy (CIN) and nephrogenic systemic fibrosis (NSF), respectively; and discusses various clinical strategies to minimize the risk of CIN and NSF. Specifically, renal imaging strategies aimed to minimize the adverse effects of contrast media as well as alternatives to iodinated and gadolinium-based contrast-enhanced renal imaging are proposed with emphasis on non-contrast-enhanced magnetic resonance imaging.

Hepatic surface nodularity is commonly seen at imaging in fulminant hepatic failure and usually reflects a combination of alternating foci of confluent regenerative nodules and necrosis; this is important because an erroneous radiologic diagnosis of cirrhosis in this setting could adversely affect transplantation status.

No abstract