bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progress in SPECT/CT Imaging of Prostate Cancer
Authors: Seo Youngho , Franc Benjamin L. , Hawkins Randall A. , Wong Kenneth H. , Hasegawa Bruce H. 
Published: October 2014

Prostate cancer is the most common type of cancer (other than skin cancer) among men in the United States. Although prostate cancer is one of the few cancers that grow so slowly that it may never threaten the lives of some patients, it can be lethal once metastasized. Indium-111 capromab pendetide (ProstaScint®, Cytogen Corporation, Princeton, NJ) imaging is indicated for staging and recurrence detection of the disease, and is particularly useful to determine whether or not the disease has spread to distant metastatic sites. However, the interpretation of 111 In-capromab pendetide is challenging without correlated structural information mostly because the radiopharmaceutical demonstrates nonspecific uptake in the normal vasculature, bowel, bone marrow, and the prostate gland. We developed an improved method of imaging and localizing 111 In-Capromab pendetide using a SPECT/CT imaging system. The specific goals included: i) development and application of a novel iterative SPECT reconstruction algorithm that utilizes a priori information from coregistered CT; and ii) assessment of clinical impact of adding SPECT/CT for prostate cancer imaging with capromab pendetide utilizing the standard and novel reconstruction techniques. Patient imaging studies with capromab pendetide were performed from 1999 to 2004 using two different SPECT/CT scanners, a prototype SPECT/CT system and a commercial SPECT/CT system (Discovery VH, GE Healthcare, Waukesha, WI). SPECT projection data from both systems were reconstructed using an experimental iterative algorithm that compensates for both photon attenuation and collimator blurring. In addition, the data obtained from the commercial system were reconstructed with attenuation correction using an OSEM reconstruction supplied by the camera manufacturer for routine clinical interpretation. For 12 sets of patient data, SPECT images reconstructed using the experimental algorithm were interpreted separately and compared with interpretation of images obtained using the standard reconstruction technique. The experimental reconstruction algorithm improved spatial resolution, reduced streak artifacts, and yielded a better correlation with anatomic details of CT in comparison to conventional reconstruction methods ( e.g., filtered back-projection or OSEM with attenuation correction only). Images produced with the experimental algorithm produced a subjective improvement in the confidence of interpretation for 11 of 12 studies. There were also changes in interpretations for 4 of 12 studies although the changes were not sufficient to alter prognosis or the patient treatment plan.
Clinical Implementation of Adaptive Helical Tomotherapy: A Unique Approach to Image-Guided Intensity Modulated Radiotherapy
Authors: Welsh James S. , Lock Michael , Harari Paul M. , Tomé Wolfgang A. , Fowler Jack , Mackie Thomas Rockwell , Ritter Mark , Kapatoes Jeff , Forrest Lisa , Chappell Richard , Paliwal Bhudatt , Mehta Minesh P. 
Published: October 2014

Image-guided IMRT is a revolutionary concept whose clinical implementation is rapidly evolving. Methods of executing beam intensity modulation have included individually designed compensators, static multi-leaf collimators (MLC), dynamic MLC, and sequential (serial) tomotherapy. We have developed helical tomotherapy as an innovative solution to overcome some of the limitations of other IMRT systems. The unique physical design of helical tomotherapy allows the realization of the concepts of adaptive radiotherapy and conformal avoidance. In principle, these advances should improve normal tissue sparing and permit dose reconstruction and verification, thereby allowing significant biologically effective dose escalation. Recent radiobiological findings can be translated into altered fractionation schemes that aim to improve the local control and long-term survival. This strategy is being tested at the University of Wisconsin using helical tomotherapy with its highly precise delivery and verification system along with meticulous and practical forms of immobilization. Innovative techniques such optical guidance, respiratory gating, and ultrasound assessments are being designed and tailored for helical tomotherapy use. The intrinsic capability of helical tomotherapy for megavoltage CT (MVCT) imaging for IMRT image-guidance is being optimized. The unique features of helical tomotherapy might allow implementation of image-guided IMRT that was previously impossible or impractical. Here we review the technological, physical, and radiobiological rationale for the ongoing and upcoming clinical trials that will use image-guided IMRT in the form of helical tomotherapy; and we describe our plans for testing our hypotheses in a rigorous prospective fashion.
In Vivo Tumor Imaging in Mice Using a State-of-the-Art Clinical PET/CT in Comparison with a Small Animal PET and a Small Animal CT
Authors: Seemann Marcus D. , Beck Roswitha , Ziegler Sibylle 
Published: October 2014

The aim of this prospective study was to assess the feasibility of a state-of-the-art clinical PET/CT scanner for in vivo tumor imaging in mice in comparison to a small animal PET scanner and a small animal CT scanner. Seventeen female NMRI nude mice bearing a subcutaneous transplanted murine mammary carcinoma (EMT6) on the right hind limb were examined using a clinical PET/CT scanner (biograph Sensation 16®), a dedicated small animal PET scanner (MOSAIC® system), and a dedicated small animal CT scanner (MicroCAT® II). 18F-fluoroazomycin arabinoside (18F-FAZA) was used as PET tracer for imaging of regional tumor hypoxia. The examination of tumor-bearing mice using a state-of-the-art clinical PET/CT scanner, a dedicated small animal PET scanner and a dedicated small animal CT scanner revealed good image quality and allowed the evaluation and correlation of molecular/metabolic alterations of cancers with anatomical/morphological findings. The tumor lesions showed a 1.89 ± 0.6 higher mean tumor-to-background ratio ± SD for the dedicated small animal PET scanner than the PET from the clinical PET/CT scanner (P<0.001). The mean tumor-to-background ratio of the PET of the clinical PET/CT scanner showed a high correlation with the mean tumor-to-background ratio of the dedicated small animal PET scanner (r2 = 0.92). The tissue hypoxia in the subcutaneous transplanted EMT6 tumors did not correlate with the tumor volume. Clinical PET/CT scanners are widely available and could contribute not only to human clinical routine examinations, but also to tumor research in animals. The molecular/metabolic information is reduced when imaging small tumors of mice with clinical PET/CT scanners due to the low spatial resolution and sensitivity of the PET scanners. The examination of small tumors in mice should be resevered to research centers with small animal PET/CT scanners because they provide promising hope to achieve accurate measurement of activity concentration. For tumor research in humans and animals using clinical PET/CT scanners, PET scanners with a higher spatial resolution and a higher sensitivity will be highly promising, but will be in competition to PET/MRI.
Development of a Tissue Engineered Human Prostate Tumor Equivalent for Use in the Evaluation of Cryoablative Techniques
Authors: Robilotto Anthony T. , Clarke Dominic , Baust John M. , Van Buskirk Robert G. , Gage Andrew A. , Baust John G. 
Published: October 2014

The study of the effectiveness of cryotherapy as a curative treatment for prostate cancer has often relied on the use of either in vitro cell culture monolayers or animal models. While the data gleaned from these studies have been valuable, each model has inherent limitations. In order to bridge the gap between in vitro studies and clinical applications, we developed a 3-dimensional, tissue engineered human prostate cancer model to simulate and assess the effects of cryotherapy and adjunctive treatments on cell viability and activation of cell death pathways throughout the thermally variable freeze zone. Human prostate cancer cells (PC3) were seeded into collagen based matrices and cryolesions were generated using an Oncura SeedNet® Gold cryosurgical device with 17-gauge cryoprobes. Analyses revealed widespread necrosis diminishing towards the edge of the freeze zone, and a time-dependent wave of apoptosis starting as early as 1 hr post-thaw at low temperatures (< −40°C) and moving toward the periphery (−20°C) as recovery times reached 12 and 24 hr. Distal to the −10°C isotherm, minimal cell death was apparent (< 20%) over controls. The adjunctive use of chemotherapeutic agents in conjunction with cryosurgery displayed a similar induction of cell death cascades, but with the zone of cryodestruction extending ~10 to 15°C further into the freeze zone periphery. By providing an extracellular environment and a matrix to minimize innate variables, the tissue engineered model yielded a more in vivo-like, tumor-like environment supportive of a deeper understanding of the specific biological responses of cancer cells/tumors to cryotherapeutic intervention.
Confocal Microscopy and Molecular-Specific Optical Contrast Agents for the Detection of Oral Neoplasia
Authors: Carlson Alicia L. , Gillenwater Ann M. , Williams Michelle D. , El-Naggar Adel K. , Richards-Kortum R. R. 
Published: October 2014

Using current clinical diagnostic techniques, it is difficult to visualize tumor morphology and architecture at the cellular level, which is necessary for diagnostic localization of pathologic lesions. Optical imaging techniques have the potential to address this clinical need by providing real-time, sub-cellular resolution images. This paper describes the use of dual mode confocal microscopy and optical molecular-specific contrast agents to image tissue architecture, cellular morphology, and sub-cellular molecular features of normal and neoplastic oral tissues. Fresh tissue slices were prepared from 33 biopsies of clinically normal and abnormal oral mucosa obtained from 14 patients. Reflectance confocal images were acquired after the application of 6% acetic acid, and fluorescence confocal images were acquired after the application of a fluorescence contrast agent targeting the epidermal growth factor receptor (EGFR). The dual imaging modes provided images similar to light microscopy of hematoxylin and eosin and immunohistochemistry staining, but from thick fresh tissue slices. Reflectance images provided information on the architecture of the tissue and the cellular morphology. The nuclear-to-cytoplasmic (N/C) ratio from the reflectance images was at least 7.5 times greater for the carcinoma than the corresponding normal samples, except for one case of highly keratinized carcinoma. Separation of carcinoma from normal and mild dysplasia was achieved using this ratio (p<0.01). Fluorescence images of EGFR expression yielded a mean fluorescence labeling intensity (FLI) that was at least 2.7 times higher for severe dysplasia and carcinoma samples than for the corresponding normal sample, and could be used to distinguish carcinoma from normal and mild dysplasia (p<0.01). Analyzed together, the N/C ratio and the mean FLI may improve the ability to distinguish carcinoma from normal squamous epithelium.
A Non-invasive, in Vivo Technique for Monitoring Vascular Status of Glioblastoma during Angiogenesis
Authors: Saxena Vishal , Gonzalez-Gomez Ignacio , Laug Walter E 
Published: October 2014

The growth of solid tumors dependent on the process of angiogenesis in which growth factors secreted by tumor and stromal cells promote endothelial cell proliferation, migration, and maturation. This process generates a tumor-specific vascular supply and enables small or dormant tumors to grow rapidly with exponential increases in tumor volume. Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis, and therapeutic response, and will facilitate to develop protocols for studying tumor behavior. A non-invasive multi-modality approach based on near infrared spectroscopy (NIRS) technique, namely: Steady State Diffuse Optical Spectroscopy (SSDOS) along with Magnetic Resonance Imaging (MRI) is applied for monitoring the concentration of oxyhemoglobin, deoxyhemoglobin and water within tumor region and for studying the vascular status of tumor and the patho-physiological changes that occur during angiogenesis. Since, the growth of solid tumors depends on the formation of new blood vessels, an association between intramural microvessel density (MVD) and tumor oxygenation is also investigated. The relative decrease in oxygenation value with tumor growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present.
A New Preclinical 3-Dimensional Agarose Colony Formation Assay
Authors: Kajiwara Yoshinori , Panchabhai Sonali , Levin Victor A. 
Published: October 2014

The evaluation of new drug treatments and combination treatments for gliomas and other cancers requires a robust means to interrogate wide dose ranges and varying times of drug exposure without stain-inactivation of the cells (colonies). To this end, we developed a 3-dimensional (3D) colony formation assay that makes use of GelCount™ technology, a new cell colony counter for gels and soft agars. We used U251MG, SNB19, and LNZ308 glioma cell lines and MiaPaCa pancreas adenocarcinoma and SW480 colon adenocarcinoma cell lines. Colonies were grown in a two-tiered agarose that had 0.7% agarose on the bottom and 0.3% agarose on top. We then studied the effects of DFMO, carboplatin, and SAHA over a 3-log dose range and over multiple days of drug exposure. Using GelCount we approximated the area under the curve (AUC) of colony volumes as the sum of colony volumes (μm2 × OD) in each plate to calculate IC50 values. Adenocarcinoma colonies were recognized by GelCount™ scanning at 3–4 days, while it took 6–7 days to detect glioma colonies. The growth rate of MiaPaCa and SW480 cells was rapid, with 100 colonies counted in 5–6 days; glioma cells grew more slowly, with 100 colonies counted in 9–10 days. Reliable log dose versus AUC curves were observed for all drugs studied. In conclusion, the GelCount™ method that we describe is more quantitative than traditional colony assays and allows precise study of drug effects with respect to both dose and time of exposure using fewer culture plates.
The Secret Marriage between Calcium and Tumor Angiogenesis
Authors: Munaron Luca , Tomatis Cristiana , Pla Alessandra Fiorio 
Published: October 2014

Endothelial cell biochemistry and responsiveness to a wide variety of external stimula are regulated by intracellular calcium concentration. During the last twenty years, electrophysiology and functional imaging based on the use of fluorescent probes provided several informations about the dynamics and role of calcium at the single cell level: highly diverse extracellular agonists, such as proangiogenic growth factors and vasoactive compounds, trigger increases in intracellular calcium and specific informations are transduced for proliferation, differentiation, death, movement in physiological and pathological conditions. Obviously, the investigation at multicellular and tissutal levels is much more complex. In this review we discuss the potential specific roles of calcium signaling in tumor angiogenesis progression trying to address two key questions: (i) how can this ion play specific roles in the angiogenesis regulation; and (ii) could it be used as a target to interfere with or prevent tumor vascularization?
Development of a Streamlined, Non-invasive Robotic Radiosurgery Method for Treatment of Uveal Melanoma
Authors: Muacevic Alexander , Nentwich Martin , Wowra Berndt , Staerk Sibylle , Kampik Anselm , Schaller Ulrich 
Published: October 2014

To analyze the feasibility and safety of frameless, image-guided robotic radiosurgery against uveal melanoma, we developed a streamlined procedure that is completed within 3 hours under retrobulbar anesthesia without immobilization. Twenty patients (10 men and 10 women) with medium (3–5-mm prominence) and large (>5-mm prominence) unilateral uveal melanomas were treated with a frameless robotic radiosurgery system. Median age was 61 years (range 32–78 years). All patients underwent a single-session procedure beginning with retrobulbar anaesthesia, followed by computerized tomography (CT) scanning that was used in the generation of a treatment plan, and then the delivery of a radiosurgical tumor dose between 18 and 22 Gy to the 70% isodose line. Three-dimensional treatment planning was aimed at securing the optical lens and the optic disc as much as possible. Follow-up occurred at 3, 6, 12, and 18 months after the radiosurgery with clinical, ultrasound, and CT studies. We were able to treat all patients in the frameless setup within 3 hours. In five patients with lateral and dorsal tumors, the dose to the optic lens could be kept below 2 Gy. The clinical response was evaluated for the first seven patients treated with a follow-up of at least 6 months. No local recurrences occurred with any of the clinically evaluated patients for a mean 13-month follow-up (range 6–22 months). Maximum median apical tumor height according to standardized A-scan ultrasound evaluations decreased from 7.7 to 5.6 mm (p < 0.1). The median reflectivity increased from 41% to 70% (p < 0.01). None of the patients developed a secondary glaucoma during the short-term follow-up period. Frameless, single-session, image-guided robotic radiosurgery is a feasible, safe and comfortable treatment option for patients with uveal melanoma. Longer follow-up and analysis of a larger patient series is required for definitive clinical recommendations.
Multimodal Cancer Treatment: Real Time Monitoring, Optimization, and Synergistic Effects
Authors: Myhr Gunnar 
Published: October 2014

The primary objective of this analysis is to provide the theoretical framework for a novel multimodal cancer treatment system emphasizing the use of ultrasound as a synergistic drug release mechanism, real time monitoring by MRI of hyperthermic, pO2, and ultrasound induced released effects. The aim is to provide a cure for the 20% of cancer victims who will die of complications from local solid tumors. Adjuvant therapy usually refers to surgery preceding or following chemotherapy and/or ionizing radiation treatment to decrease the risk of recurrence, but the absolute benefit for survival obtained with adjuvant therapy compared to control is only approximately 6%. Tumor hypoxia represents a primary therapeutic concern, besides multi-drug resistance (MDR), because it can reduce the effectiveness of drugs and radiotherapy; well-oxygenated cells require one-third the dose of hypoxic cells to achieve a given level of cell killing. The era of systemic and indiscriminate chemotherapeutic drug delivery into both healthy and pathologic tissues is near an end. Targeted drug delivery using nanoparticles is emerging as the new vehicle, either as a single treatment option, as part of adjuvant procedures or as a component of a multimodal cancer treatment system. There are more than 100 nanosized liposomes or particles, and conjugated anticancer agents in various stages of preclinical and clinical development. Active targeting can be achieved by site-specific delivery or site-specific triggering. Ultrasound can be utilized as both a site triggering and synergistic mechanism in drug release. The process can be monitored using MRI by a physical process called cavitation. An analysis of low frequency ultrasound exposure in combination with liposomally encapsulated doxorubicin (Caelyx) on Balb/c nude mice inoculated with a WiDr (human colon cancer) tumor cell line provided tumor growth inhibition of 30–40%. Mild hyperthermia causes mean intratumor pO2 to increase by 25% and enhances tumor radiosensitization. Hyperthermia causes the extravasation of liposome nanoparticles in deep tumor regions. Ionizing radiation improves the distribution and uptake of drugs. Liposomally encapsulated drugs and ultrasound mediated hyperthermia have been proven to circumvent MDR effects. Hyperthermic effects and pO2 monitoring of bodily fluid have been performed by MRI. It is hypothesized that increased vascularization and subsequent increase in pO2 levels to hypoxic regions, and monitoring of drug release through cavitation, can facilitate optimized real time concomitant or sequential treatments of drug therapy, hyperthermia, ionizing radiation, etc., before or after surgery. An improved therapeutic index with the use of the outlined system seems probable.
Dose Escalated, Hypofractionated Radiotherapy Using Helical Tomotherapy for Inoperable Non-Small Cell Lung Cancer: Preliminary Results of a Risk-Stratified Phase I Dose Escalation Study
Authors: Adkison Jarrod B. , Khuntia Deepak , Bentzen Søren M. , Cannon George M. , Tome Wolfgang A. , Jaradat Hazim , Walker Wendy , Traynor Anne M. , Weigel Tracey , Mehta Minesh P. 
Published: October 2014

To improve local control for inoperable non-small cell lung cancer (NSCLC), a phase I dose escalation study for locally advanced and medically inoperable patients was devised to escalate tumor dose while limiting the dose to organs at risk including the esophagus, spinal cord, and residual lung. Helical tomotherapy provided image-guided IMRT, delivered in a 5-week hypofractionated schedule to minimize the effect of accelerated repopulation. Forty-six patients judged not to be surgical candidates with Stage I-IV NSCLC were treated. Concurrent chemotherapy was not allowed. Radiotherapy was delivered via helical tomotherapy and limited to the primary site and clinically proven or suspicious nodal regions without elective nodal irradiation. Patients were placed in 1 of 5 dose bins, all treated for 25 fractions, with dose per fraction ranging from 2.28 to 3.22 Gy. The bin doses of 57 to 80.5 Gy result in 2 Gy/fraction normalized tissue dose (NTD) equivalents of 60 to 100 Gy. In each bin, the starting dose was determined by the relative normalized tissue mean dose modeled to cause < 20% Grade 2 pneumonitis. Dose constraints included spinal cord maximum NTD of 50 Gy, esophageal maximum NTD < 64 Gy to ≤ 0.5 cc volume, and esophageal effective volume of 30%. No grade 3 RTOG acute pneumonitis (NCI-CTC v.3) or esophageal toxicities (CTCAE v.3.0 and RTOG) were observed at median follow-up of 8.1 months. Pneumonitis rates were 70% grade 1 and 13% grade 2. Multivariate analysis identified lung NTDmean (p=0.012) and administration of adjuvant chemotherapy following radiotherapy (p=0.015) to be independent risk factors for grade 2 pneumonitis. Only seven patients (15%) required narcotic analgesics (RTOG grade 2 toxicity) for esophagitis, with only 2.3% average weight loss during treatment. Best in-field gross response rates were 17% complete response, 43% partial response, 26% stable disease, and 6.5% in-field thoracic progression. The out-of-field thoracic failure rate was 13%, and distal failure rate was 28%. The median survival was 18 months with 2-year overall survival of 46.8% ± 9.7% for this cohort, 50% of whom were stage IIIB and 30% stage IIIA. Dose escalation can be safely achieved in NSCLC with lower than expected rates of pneumonitis and esophagitis using hypofractionated image-guided IMRT. The maximum tolerated dose has yet to be reached.