Molecular imaging in pulmonary diseases.

OBJECTIVE: In this article, we consider a multitude of the latest techniques used for evaluating benign and malignant pulmonary diseases. Our review will include mostly clinically pertinent studies, but we have also included breakthrough basic science research that has potentially significant clinical implications. CONCLUSION: Molecular imaging enables noninvasive visualization and measurement of the dynamic molecular processes within living organisms. Early recognition of molecular and cellular malfunctions can help optimize diagnostic and therapeutic strategies.

Integrin-targeted imaging and therapy with RGD4C-TNF fusion protein.

This study used integrin alpha v beta3 as a target for tumor-specific delivery of tumor necrosis factor-alpha (TNF). The fusion protein RGD4C-TNF bound specifically to alpha v beta3 as evidenced by cell receptor binding assay and noninvasive micro-positron emission tomography imaging. 64Cu-DOTA-RGD4C-TNF had significantly higher activity accumulation in integrin-positive tumors (U87MG and MDA-MB-435) but not in integrin-negative tumors (C6) compared with 64Cu-DOTA-TNF. The magnitude of tumor uptake of 64Cu-DOTA-RGD4C-TNF correlated well with the alpha v beta3 level (U87MG > MDA-MB-435 > C6). Tumor accumulation of 64Cu-DOTA-RGD4C-TNF could be effectively blocked by c(RGDyK) peptide in alpha v beta3-positive tumor models, suggesting alpha v beta3 specificity of RGD4C-TNF fusion protein in vivo. Furthermore, although the fusion of RGD4C moiety to TNF had little effect on the bioactivity and cytotoxicity of RGD4C-TNF compared with TNF in cell culture, RGD4C-TNF was significantly more potent than TNF in inhibiting orthotopic MDA-MB-435 tumor growth. Ex vivo tissue staining confirmed specific cytotoxicity of RGD4C-TNF against integrin-positive tumor cells and tumor vasculature.

Molecular imaging as the main part of our decision-making and treatment strategies in stroke.

Review of results of clinical studies indicates the number of potential patients who are actually treated for acute ischemic stroke is disappointingly low, and effective treatments are making a minor impact on this major public health problem. Imaging modalities, such as diffusion- and perfusion-weighted images, as well as CT perfusion and CT angiography, to better select patients for treatment are now routinely performed in most academic medical centers. However, there is not a perfect penumbra imaging technique and each one has its own advantages and disadvantages. Recent advances in molecular imaging modalities allow a better understanding of this pathophysiological process that could lead to enhanced therapy for stroke. This article seeks to describe the role of molecular imaging in identifying the pathophysiology of stroke and how it could be incorporated in future decision-making and treatment strategies in stroke.

Breast cancer in Iran: results of a multi-center study.

INTRODUCTION: Breast Cancer is the most common cancer in Iranian women. This study aims to demonstrate the characteristics of breast diseases- and especially breast cancer- according to pathologic records in Tehran, Iran. METHODS: In this cross-sectional study, all records of pathologic specimens (biopsy or mastectomy) categorized as "breast diseases" from 1996 to 2000 in five teaching hospitals in Tehran were studied. For each patient, sex, age, breast pathology, pathological staging of malignant lesions, side and location of the tumor and the type of surgery were reviewed by a trained general practitioner. SPSS version 10 was used for statistical analysis. RESULTS: The mean age of women with breast cancer was 48.8. The highest frequency of malignancies was observed in the 40-49 age group (31.8%). Twenty-three percent of breast cancers were observed in women younger than 40 years. About 83 percent of malignant lesions in women were in T2, T3 or T4 at diagnosis. Only about 4 percent of women with breast cancers had tumors in stage I or in-situ carcinomas. Nearly 70 percent of the cancers were detected only after lymph node involvement. Only 4.3 percent of our female cases had the chance of conservative mastectomy. Twenty-eight percent of specimens from biopsies in women were malignant. DISCUSSION AND CONCLUSION: In Iran, breast cancer affects women at least one decade younger than their counterparts in developed countries. A considerable proportion of our cases (96%) were in stage II or III at diagnosis. These results show advanced cases at presentation in Iran which further mandate a national cancer detection program involving more effective public education and encouragement of women for breast self-examination and participation in screening campaigns.

Scatter-search with support vector machine for prediction of relative solvent accessibility.

Proteins have vital roles in the living cells. The protein function is almost completely dependent on protein structure. The prediction of relative solvent accessibility gives helpful information for the prediction of tertiary structure of a protein. In recent years several relative solvent accessibility (RSA) prediction methods including those that generate real values and those that predict discrete states have been developed. The proposed method consists of two main steps: the first one, provided subset selection of quantitative features based on selected qualitative features and the second, dedicated to train a model with selected quantitative features for RSA prediction. The results show that the proposed method has an improvement in average prediction accuracy and training time. The proposed method can dig out all the valuable knowledge about which physicochemical features of amino acids are deemed more important in prediction of RSA without human supervision, which is of great importance for biologists and their future researches.

Clinical response of pelvic and para-aortic lymphadenopathy to a radiation boost in the definitive management of locally advanced cervical cancer.

PURPOSE: Optimal treatment with radiation for metastatic lymphadenopathy in locally advanced cervical cancer remains controversial. We investigated the clinical dose response threshold for pelvic and para-aortic lymph node boost using radiographic imaging and clinical outcomes. METHODS AND MATERIALS: Between 2007 and 2011, 68 patients were treated for locally advanced cervical cancer; 40 patients had clinically involved pelvic and/or para-aortic lymph nodes. Computed tomography (CT) or 18F-labeled fluorodeoxyglucose-positron emission tomography scans obtained pre- and postchemoradiation for 18 patients were reviewed to assess therapeutic radiographic response of individual lymph nodes. External beam boost doses to involved nodes were compared to treatment response, assessed by change in size of lymph nodes by short axis and change in standard uptake value (SUV). Patterns of failure, time to recurrence, overall survival (OS), and disease-free survival (DFS) were determined. RESULTS: Sixty-four lymph nodes suspicious for metastatic involvement were identified. Radiation boost doses ranged from 0 to 15 Gy, with a mean total dose of 52.3 Gy. Pelvic lymph nodes were treated with a slightly higher dose than para-aortic lymph nodes: mean 55.3 Gy versus 51.7 Gy, respectively. There was no correlation between dose delivered and change in size of lymph nodes along the short axis. All lymph nodes underwent a decrease in SUV with a complete resolution of abnormal uptake observed in 68%. Decrease in SUV was significantly greater for lymph nodes treated with ≥54 Gy compared to those treated with <54 Gy (P=.006). Median follow-up was 18.7 months. At 2 years, OS and DFS for the entire cohort were 78% and 50%, respectively. Locoregional control at 2 years was 84%. CONCLUSIONS: A biologic response, as measured by the change in SUV for metastatic lymph nodes, was observed at a dose threshold of 54 Gy. We recommend that involved lymph nodes be treated to this minimum dose.

Decreasing trend of tumor size and downstaging in breast cancer in Iran: results of a 15-year study.

The aim of this cross-sectional study was to show the characteristics of breast cancer across a period of 15 years according to pathological records in Tehran, Iran. In the year 1985, a 20-year study was designed and developed in five major hospitals in Tehran to study the burden and characteristics of breast cancer in Iran. This study is based on the data collected from 1986 through 2000. SPSS version 13 was used for statistical analysis. In this study, 1612 female breast cancer records were reviewed. The mean age of patients was 47.95+/-12.42 years with a median of 47 years. Over the study period, the proportion of tumors diagnosed at T2 increased with a decline in the proportion of T3 cases. Similarly, the percentage of stage II cases at diagnosis increased, whereas stage III decreased. We detected a decrease in tumor size and downstaging of female breast cancer in Tehran, Iran. This can be attributed to the overall improvement in the level of health in Iran and also educational activities that teach women how to perform breast self-exam and when and why to ask for breast examination.

A new PET tracer specific for vascular endothelial growth factor receptor 2.

PURPOSE: Noninvasive positron emission tomography (PET) imaging of vascular endothelial growth factor receptor 2 (VEGFR-2) expression could be a valuable tool for evaluation of patients with a variety of malignancies, and particularly for monitoring those undergoing antiangiogenic therapies that block VEGF/VEGFR-2 function. The aim of this study was to develop a VEGFR-2-specific PET tracer. METHODS: The D63AE64AE67A mutant of VEGF(121) (VEGF(DEE)) was generated by recombinant DNA technology. VEGF(121) and VEGF(DEE) were purified and conjugated with DOTA for (64)Cu labeling. The DOTA conjugates were tested in vitro for VEGFR-2 specificity and functional activity. In vivo tumor targeting efficacy and pharmacokinetics of (64)Cu-labeled VEGF(121) and VEGF(DEE) were compared using an orthotopic 4T1 murine breast tumor model. Blocking experiments, biodistribution studies, and immunofluorescence staining were carried out to confirm the noninvasive imaging results. RESULTS: Cell binding assay demonstrated that VEGF(DEE) had about 20-fold lower VEGFR-1 binding affinity and only slightly lower VEGFR-2 binding affinity as compared with VEGF(121). MicroPET imaging studies revealed that both (64)Cu-DOTA-VEGF(121) and (64)Cu-DOTA-VEGF(DEE) had rapid and prominent activity accumulation in VEGFR-2-expressing 4T1 tumors. The renal uptake of (64)Cu-DOTA-VEGF(DEE) was significantly lower than that of (64)Cu-DOTA-VEGF(121) as rodent kidneys expressed high levels of VEGFR-1 based on immunofluorescence staining. Blocking experiments and biodistribution studies confirmed the VEGFR specificity of (64)Cu-DOTA-VEGF(DEE). CONCLUSION: We have developed a VEGFR-2-specific PET tracer, (64)Cu-DOTA-VEGF(DEE). It has comparable tumor targeting efficacy to (64)Cu-DOTA-VEGF(121) but much reduced renal toxicity. This tracer may be translated into the clinic for imaging tumor angiogenesis and monitoring antiangiogenic treatment efficacy.