Biodegradable Radiofrequency Responsive Nanoparticles for Augmented Thermal Ablation Combined with Triggered Drug Release in Liver Tumors.

Radiofrequency ablation (RFA) and doxorubicin (Dox) chemotherapy are separately approved for liver cancer therapy; however, both have limited success in the clinic due to suboptimal/nonuniform heating and systemic side effects, respectively. Here, we report a biodegradable nanoparticle (NP) system showing excellent RF hyperthermic response together with the ability to locally deliver Dox in the liver under RF trigger and control. The nanosystem was prepared by doping a clinically permissible dose (∼4.3 wt %, 0.03 ppm) of stannous ions in alginate nanoparticles (∼100 nm) coloaded with Dox at ∼13.4 wt % concentration and surface conjugated with galactose for targeting asialo-glycoprotein receptors in liver tumors. Targeted NP-uptake and increased cytotoxicity when combined with RF exposure was demonstrated in HEPG2 liver cancer cells. Following in vitro (chicken liver phantom) demonstration of locally augmented RF thermal response, in vivo scintigraphic imaging of 99Tc-labeled NPs was performed to optimize liver localization in Sprague-Dawley (SD) rats. RF ablation was performed in vivo using a cooled-tip probe, and uniformly enhanced (∼44%) thermal ablation was demonstrated with magnetic resonance imaging along with RF-controlled Dox release. In orthotopic rat liver tumor models, real-time infrared imaging revealed significantly higher (∼20 °C) RF thermal response at the tumor site, resulting in uniform augmented ablation (∼80%) even at a low RF power exposure of 15 W for just 1 min duration. Being a clinically acceptable, biodegradable material, alginate nanoparticles hold strong translational potential for augmented RF hyperthermia combined with triggered drug release.

Multifunctional calcium phosphate nano-contrast agent for combined nuclear, magnetic and near-infrared in vivo imaging.

Combination of three imaging techniques such as nuclear, magnetic and near-infrared fluorescence can aid in improved diagnosis of disease by synergizing specific advantages of each of these techniques such as deep tissue penetration of radiation signals, anatomical and functional details provided by magnetic contrast and better spatial resolution of optical signals. In the present work, we report the development of a multimodal contrast agent based on calcium phosphate nanoparticles (nCP), doped with both indocyanine green (ICG) and Gadolinium (Gd(3+)), and labeled with 99m-Technetium-methylene diphosphonate ((99m)Tc-MDP) for combined optical, magnetic and nuclear imaging. In order to obtain the desired tri-modal contrast properties, the concentrations of ICG, Gd(3+) and (99m)Tc were optimized at ∼0.15wt%, 3.38at% and ∼0.002ng/mg of nCP, respectively. The leaching-out of ICG was protected by an additional coating of polyethyleneimine (PEI). Toxicological evaluation of the final construct carried out on healthy human mononuclear cells, red-blood cells and platelets, showed excellent hemocompatibility. In vivo multimodal imaging using mice models revealed the ability to provide near-infrared, magnetic and nuclear contrast simultaneously. The nanoparticles also showed the potential for improved MR based angio-imaging of liver. Retention of intravenously administrated nanoparticles in the liver was reduced with PEGylation and the clearance was observed within 48h without causing any major histological changes in vital organs. Thus, we developed a non-toxic tri-modal nano-contrast agent using calcium phosphate nanoparticles and demonstrated its potential for combined nuclear, magnetic and near-infrared imaging in vivo.

Random Synchronous Malignancy in Male Breast: A Case Report / 한국유방암학회지

We report here a case of a random synchronous male breast malignancy in a patient with a known base of tongue malignancy that was incidentally detected on a whole body 18-fluorine deoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT). Patient was referred to us for PET/CT staging and radiotherapy planning for a poorly differentiated squamous cell carcinoma of base of tongue. Histopathologically, the incidentally detected breast lesion was proven to be an invasive ductal carcinoma. 18F-FDG PET/CT being a whole body imaging modality is known to detect a considerable number of synchronous primaries. Synchronous malignancies in the head and neck area and the upper aerodigestive tract are well established. However, synchronous malignancy in male breast is reportedly uncommon. Our case is unique for the fact that a random synchronous dual malignancy of base of tongue and breast in a male patient was detected during a whole body 18F-FDG PET/CT imaging.

Salivagram revisited: justifying its routine use for the evaluation of persistent/recurrent lower respiratory tract infections in developmentally normal children.

PURPOSE: To assess and establish the utility of radionuclide salivagram in the routine evaluation of developmentally normal children with persistent/recurrent lower respiratory tract infection. METHODS: 113 neurodevelopmentally normal children diagnosed with persistent/recurrent lower respiratory tract infection underwent a salivagram and a milk scan on two consecutive days. Frequency of detection of pulmonary aspiration by either procedure individually and increment in detection rates on combining the two were assessed. The agreement between the tests was also studied. RESULTS: Antegrade pulmonary aspiration was demonstrated using the salivagram in 39.2 % of infants and 16.1 % of children between the ages of 1 and 2 years. No antegrade aspiration was seen in children above the age of 2 years. 44 % of all antegrade aspirations identified were bilateral, while remaining 66 % were into the right lung. Milk scan revealed gastroesophageal reflux in 38 % of children and most commonly in those above the age of 2 years. Diagnosis of pulmonary aspiration as an underlying cause of the lung pathology increased from 38 % with the use of milk scan alone to 53.9 % on combining the procedures. There was a poor agreement between the two procedures (kappa -0.103). CONCLUSION: Antegrade pulmonary aspiration can be demonstrated as an underlying cause for persistent/recurrent lower respiratory tract infection in developmentally normal children, with age being an important clinical predictor. Combined use of salivagram and milk scan is warranted to objectively evaluate pulmonary aspiration in children.