Can Choline PET Tackle the Challenge of Imaging Prostate Cancer?

Positron emission tompography with radiolabeled (with 11C- or 18F-) choline has received much attention, particularly in Europe and Japan, over the past several years. While monitoring cellular membrane lipogenesis with radiolabeled choline is nonspecific for cancer, the malignancy-induced increased demand for cellular membrane synthesis can be a useful feature for imaging-based diagnosis and treatment evaluation. Many choline PET(/CT) studies have focused on prostate cancer given that 18F-flurodeoxyglucose appears to be primarily useful in progressive metastatic disease and is overall limited in the initial staging of disease or for evaluation of men with biochemical recurrence. The current evidence suggests that choline PET(/CT), particularly the 18F- label, may become routinely available, initially in many European countries, for the clinical imaging evaluation of men with prostate cancer

Alpha-particle-induced complex chromosome exchanges transmitted through extra-thymic lymphopoiesis in vitro show evidence of emerging genomic instability

Human exposure to high-linear energy transfer α-particles includes environmental (e.g. radon gas and its decay progeny), medical (e.g. radiopharmaceuticals) and occupational (nuclear industry) sources. The associated health risks of α-particle exposure for lung cancer are well documented however the risk estimates for leukaemia remain uncertain. To further our understanding of α-particle effects in target cells for leukaemogenesis and also to seek general markers of individual exposure to α-particles, this study assessed the transmission of chromosomal damage initially-induced in human haemopoietic stem and progenitor cells after exposure to high-LET α-particles. Cells surviving exposure were differentiated into mature T-cells by extra-thymic T-cell differentiation in vitro. Multiplex fluorescence in situ hybridisation (M-FISH) analysis of naïve T-cell populations showed the occurrence of stable (clonal) complex chromosome aberrations consistent with those that are characteristically induced in spherical cells by the traversal of a single α-particle track. Additionally, complex chromosome exchanges were observed in the progeny of irradiated mature T-cell populations. In addition to this, newly arising de novo chromosome aberrations were detected in cells which possessed clonal markers of α-particle exposure and also in cells which did not show any evidence of previous exposure, suggesting ongoing genomic instability in these populations. Our findings support the usefulness and reliability of employing complex chromosome exchanges as indicators of past or ongoing exposure to high-LET radiation and demonstrate the potential applicability to evaluate health risks associated with α-particle exposure.This work was supported by the Department of Health, UK. Contract RRX95 (RMA NSDTG)

Computer analysis of the electrocardiogram for detection of myocardial ischemia during transesophageal atrial pacing stress

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43996/1/10439_2006_Article_BF02368039.pd

Value of EUS in Determining Curative Resectability in Reference to CT and FDG-PET: The Optimal Sequence in Preoperative Staging of Esophageal Cancer?

Background: The separate value of endoscopic ultrasonography (EUS), multidetector computed tomography (CT), and18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the optimal sequence in staging esophageal cancer has not been investigated adequately. Methods: The staging records of 216 consecutive operable patients with esophageal cancer were reviewed blindly. Different staging strategies were analyzed, and the likelihood ratio (LR) of each module was calculated conditionally on individual patient characteristics. A logistic regression approach was used to determine the most favorable staging strategy. Results: Initial EUS results were not significantly related to the LRs of initial CT and FDG-PET results. The positive LR (LR+) of EUS-fine-needle aspiration (FNA) was 4, irrespective of CT and FDG-PET outcomes. The LR+ of FDG-PET varied from 13 (negative CT) to 6 (positive CT). The LR+ of CT ranged from 3-4 (negative FDG-PET) to 2-3 (positive FDG-PET). Age, histology, and tumor length had no significant impact on the LRs of the three diagnostic tests. Conclusions: This study argues in favor of PET/CT rather than EUS as a predictor of curative resectability in esophageal cancer. EUS does not correspond with either CT or FDG-PET. LRs of FDG-PET were substantially different between subgroups of negative and positive CT results and vice versa

Role of monocarboxylate transporters in human cancers : state of the art

Monocarboxylate transporters (MCTs) belong to the SLC16 gene family, presently composed by 14 members. MCT1-MCT4 are proton symporters, which mediate the transmembrane transport of pyruvate, lactate and ketone bodies. The role of MCTs in cell homeostasis has been characterized in detail in normal tissues, however, their role in cancer is still far from understood. Most solid tumors are known to rely on glycolysis for energy production and this activity leads to production of important amounts of lactate, which are exported into the extracellular milieu, contributing to the acidic microenvironment. In this context, MCTs will play a dual role in the maintenance of the hyper-glycolytic acidresistant phenotype of cancer, allowing the maintenance of the high glycolytic rates by performing lactate efflux, and pH regulation by the co-transport of protons. Thus, they constitute attractive targets for cancer therapy, which have been little explored. Here we review the literature on the role of MCTs in solid tumors in different locations, such as colon, central nervous system, breast, lung, gynecologic tract, prostate, stomach, however, there are many conflicting results and in most cases there are no functional studies showing the dependence of the tumors on MCT expression and activity. Additional studies on MCT expression in other tumor types, confirmation of the results already published as well as additional functional studies are needed to deeply understand the role of MCTs in cancer maintenance and aggressiveness

Targeted Radionuclide Therapy: Practical Applications and Future Prospects

In recent years, there has been a proliferation in the development of targeted radionuclide cancer therapy. It is now possible to use baseline clinical and imaging assessments to determine the most effective therapy and to tailor this therapy during the course of treatment based on radiation dosimetry and tumor response. Although this personalized approach to medicine has the advantage of maximizing therapeutic effect while limiting toxicity, it can be challenging to implement and expensive. Further, in order to use targeted radionuclide therapy effectively, there is a need for multidisciplinary awareness, education, and collaboration across the scientific, industrial, and medical communities. Even more important, there is a growing understanding that combining radiopharmaceuticals with conventional treatment such as chemotherapy and external beam radiotherapy may limit patient morbidity while improving survival. Developments in radiopharmaceuticals as biomarkers capable of predicting therapeutic response and targeting disease are playing a central role in medical research. Adoption of a practical approach to manufacturing and delivering radiopharmaceuticals, assessing patient eligibility, optimizing post-therapy follow-up, and addressing reimbursement issues will be essential for their success

Detecting the Recurrence of Gastric Cancer after Curative Resection: Comparison of FDG PET/CT and Contrast-Enhanced Abdominal CT

The purpose of this study was to evaluate the value of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) for detecting the recurrence of gastric cancer. We performed a retrospective review of 139 consecutive patients who underwent PET/CT and contrast-enhanced abdominal CT (CECT) for surveillance of gastric cancer after curative resection. Recurrence of gastric cancer was validated by histopathologic examination for local recurrence or serial imaging study follow-up with at least 1 yr interval for recurrence of distant metastasis form. Twenty-eight patients (20.1%) were confirmed as recurrence. On the patient based analysis, there was no statistically significant difference in the sensitivity, specificity and accuracy of PET/CT (53.6%, 84.7%, and 78.4%, respectively) and those of CECT (64.3%, 86.5%, and 82.0%, respectively) for detecting tumor recurrence except in detection of peritoneal carcinomatosis. Among 36 recurrent lesions, 8 lesions (22.2%) were detected only on PET/CT, and 10 lesions (27.8%) only on CECT. PET/CT had detected secondary malignancy in 8 patients. PET/CT is as accurate as CECT in detection of gastric cancer recurrence after curative resection, excepting detection of peritoneal carcinomatosis. Moreover, additional PET/CT on CECT could improve detection rate of tumor recurrence and provide other critical information such as unexpected secondary malignancy