[18F]-Fluorinated Carboplatin and [111In]-Liposome for Image-Guided Drug Delivery.

Radiolabeled liposomes have been employed as diagnostic tools to monitor in vivo distribution of liposomes in real-time, which helps in optimizing the therapeutic efficacy of the liposomal drug delivery. This work utilizes the platform of [111In]-Liposome as a drug delivery vehicle, encapsulating a novel 18F-labeled carboplatin drug derivative ([18F]-FCP) as a dual-molecular imaging tool as both a radiolabeled drug and radiolabeled carrier. The approach has the potential for clinical translation in individual patients using a dual modal approach of clinically-relevant radionuclides of 18F positron emission tomography (PET) and 111In single photon emission computed tomography (SPECT). [111In]-Liposome was synthesized and evaluated in vivo by biodistribution and SPECT imaging. The [18F]-FCP encapsulated [111In]-Liposome nano-construct was investigated, in vivo, using an optimized dual-tracer PET and SPECT imaging in a nude mouse. The biodistribution data and SPECT imaging showed spleen and liver uptake of [111In]-Liposome and the subsequent clearance of activity with time. Dual-modality imaging of [18F]-FCP encapsulated [111In]-Liposome showed significant uptake in liver and spleen in both PET and SPECT images. Qualitative analysis of SPECT images and quantitative analysis of PET images showed the same pattern of activity during the imaging period and demonstrated the feasibility of dual-tracer imaging of a single dual-labeled nano-construct.

Diabetes mellitus and radiation induced lung injury after thoracic stereotactic body radiotherapy.

BACKGROUND: Radiographic radiation induced lung injury (RILI) is frequently observed after stereotactic body radiotherapy (SBRT). Models of radiographic change can identify patient risk factors that predict clinical toxicity. We examined the association between radiographic lung changes and lung tissue dose-density response over time with clinical risk factors for RILI, such as diabetes. METHODS: 424 baseline and follow up CT scans at 3, 6, and 12 months post-treatment were analyzed in 116 patients (27 with diabetes) undergoing thoracic SBRT. Volumes of dense/hazy regions and lung parenchyma dose-density response curves were evaluated with respect to follow up time, diabetes, and other factors. RESULTS: Dense and hazy tissue regions were larger in the diabetic population, with the effect most pronounced at 3 months. Similarly, dose-density response curves showed greater density change versus dose in the diabetic group (all p < 0.05). Diabetes, time, the interaction of diabetes and time, smoking status, African American race, baseline lung density, and tumor location were significantly associated with radiographic changes on mixed effect analyses. PTV size, pulmonary function, and medication exposure did not significantly impact RILI. Clinical grade 1-2 pneumonitis was more prevalent in diabetic patients (p = 0.02). However, radiographic change did not correlate with clinical pneumonitis. CONCLUSIONS: The presence of diabetes and other clinical factors is associated with increased volume and density of radiographic RILI after lung SBRT, most prominently early after treatment. This is the first report demonstrating the increased severity of RILI after SBRT in diabetic patients. Increased caution treating diabetic patients may be warranted.

Interobserver reliability in describing radiographic lung changes after stereotactic body radiation therapy.

PURPOSE: Radiographic lung changes after stereotactic body radiation therapy (SBRT) vary widely between patients. Standardized descriptions of acute (≤6 months after treatment) and late (>6 months after treatment) benign lung changes have been proposed but the reliable application of these classification systems has not been demonstrated. Herein, we examine the interobserver reliability of classifying acute and late lung changes after SBRT. METHODS AND MATERIALS: A total of 280 follow-up computed tomography scans at 3, 6, and 12 months post-treatment were analyzed in 100 patients undergoing thoracic SBRT. Standardized descriptions of acute lung changes (3- and 6-month scans) include diffuse consolidation, patchy consolidation and ground glass opacity (GGO), diffuse GGO, patchy GGO, and no change. Late lung change classifications (12-month scans) include modified conventional pattern, mass-like pattern, scar-like pattern, and no change. Five physicians scored the images independently in a blinded fashion. Fleiss' kappa scores quantified the interobserver agreement. RESULTS: The Kappa scores were 0.30 at 3 months, 0.20 at 6 months, and 0.25 at 12 months. The proportion of patients in each category at 3 and 6 months was as follows: Diffuse consolidation 11% and 21%; patchy consolidation and GGO 15% and 28%; diffuse GGO 10% and 11%; patchy GGO 15% and 15%; and no change 49% and 25%, respectively. The percentage of patients in each category at 12 months was as follows: Modified conventional 46%; mass-like 16%; scar-like 26%; and no change 12%. Uniform scoring between the observers occurred in 26, 8, and 14 cases at 3, 6, and 12 months, respectively. CONCLUSIONS: Interobserver reliability scores indicate a fair agreement to classify radiographic lung changes after SBRT. Qualitative descriptions are insufficient to categorize these findings because most patient scans do not fit clearly into a single classification. Categorization at 6 months may be the most difficult because late and acute lung changes can arise at that time.