Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation.

Uric acid (UA) is known to activate the NLRP3 (Nacht, leucine-rich repeat and pyrin domain containing protein 3) inflammasome. When activated, the NLRP3 (also known as NALP3) inflammasome leads to the production of IL-18 and IL-1ß. In this cohort of subjects with knee osteoarthritis (OA), synovial fluid uric acid was strongly correlated with synovial fluid IL-18 and IL-1ß. Synovial fluid uric acid and IL-18 were strongly and positively associated with OA severity as measured by both radiograph and bone scintigraphy, and synovial fluid IL-1ß was associated with OA severity but only by radiograph. Furthermore, synovial fluid IL-18 was associated with a 3-y change in OA severity, on the basis of the radiograph. We conclude that synovial fluid uric acid is a marker of knee OA severity. The correlation of synovial fluid uric acid with the two cytokines (IL-18 and IL-1ß) known to be produced by uric acid-activated inflammasomes and the association of synovial fluid IL-18 with OA progression, lend strong support to the potential involvement of the innate immune system in OA pathology and OA progression.

Predicting cognitive decline in subjects at risk for Alzheimer disease by using combined cerebrospinal fluid, MR imaging, and PET biomarkers.

PURPOSE: To assess the extent to which multiple Alzheimer disease (AD) biomarkers improve the ability to predict future decline in subjects with mild cognitive impairment (MCI) compared with predictions based on clinical parameters alone. MATERIALS AND METHODS: All protocols were approved by the institutional review board at each site, and written informed consent was obtained from all subjects. The study was HIPAA compliant. Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline magnetic resonance (MR) imaging and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) studies for 97 subjects with MCI were used. MR imaging-derived gray matter probability maps and FDG PET images were analyzed by using independent component analysis, an unbiased data-driven method to extract independent sources of information from whole-brain data. The loading parameters for all MR imaging and FDG components, along with cerebrospinal fluid (CSF) proteins, were entered into logistic regression models (dependent variable: conversion to AD within 4 years). Eight models were considered, including all combinations of MR imaging, PET, and CSF markers with the covariates (age, education, apolipoprotein E genotype, Alzheimer's Disease Assessment Scale-Cognitive subscale score). RESULTS: Combining MR imaging, FDG PET, and CSF data with routine clinical tests significantly increased the accuracy of predicting conversion to AD compared with clinical testing alone. The misclassification rate decreased from 41.3% to 28.4% (P < .00001). FDG PET contributed more information to routine tests (P < .00001) than CSF (P = .32) or MR imaging (P = .08). CONCLUSION: Imaging and CSF biomarkers can improve prediction of conversion from MCI to AD compared with baseline clinical testing. FDG PET appears to add the greatest prognostic information.

Use of florbetapir-PET for imaging beta-amyloid pathology.

CONTEXT: The ability to identify and quantify brain ß-amyloid could increase the accuracy of a clinical diagnosis of Alzheimer disease. OBJECTIVE: To determine if florbetapir F 18 positron emission tomographic (PET) imaging performed during life accurately predicts the presence of ß-amyloid in the brain at autopsy. DESIGN, SETTING, AND PARTICIPANTS: Prospective clinical evaluation conducted February 2009 through March 2010 of florbetapir-PET imaging performed on 35 patients from hospice, long-term care, and community health care facilities near the end of their lives (6 patients to establish the protocol and 29 to validate) compared with immunohistochemistry and silver stain measures of brain ß-amyloid after their death used as the reference standard. PET images were also obtained in 74 young individuals (18-50 years) presumed free of brain amyloid to better understand the frequency of a false-positive interpretation of a florbetapir-PET image. MAIN OUTCOME MEASURES: Correlation of florbetapir-PET image interpretation (based on the median of 3 nuclear medicine physicians' ratings) and semiautomated quantification of cortical retention with postmortem ß-amyloid burden, neuritic amyloid plaque density, and neuropathological diagnosis of Alzheimer disease in the first 35 participants autopsied (out of 152 individuals enrolled in the PET pathological correlation study). RESULTS: Florbetapir-PET imaging was performed a mean of 99 days (range, 1-377 days) before death for the 29 individuals in the primary analysis cohort. Fifteen of the 29 individuals (51.7%) met pathological criteria for Alzheimer disease. Both visual interpretation of the florbetapir-PET images and mean quantitative estimates of cortical uptake were correlated with presence and quantity of ß-amyloid pathology at autopsy as measured by immunohistochemistry (Bonferroni ρ, 0.78 [95% confidence interval, 0.58-0.89]; P <.001]) and silver stain neuritic plaque score (Bonferroni ρ, 0.71 [95% confidence interval, 0.47-0.86]; P <.001). Florbetapir-PET images and postmortem results rated as positive or negative for ß-amyloid agreed in 96% of the 29 individuals in the primary analysis cohort. The florbetapir-PET image was rated as amyloid negative in the 74 younger individuals in the nonautopsy cohort. CONCLUSIONS: Florbetapir-PET imaging was correlated with the presence and density of ß-amyloid. These data provide evidence that a molecular imaging procedure can identify ß-amyloid pathology in the brains of individuals during life. Additional studies are required to understand the appropriate use of florbetapir-PET imaging in the clinical diagnosis of Alzheimer disease and for the prediction of progression to dementia.

Combination of converging collimators for high-sensitivity brain SPECT.

UNLABELLED: The objective of this study, which is related to human brain SPECT, was to increase the sensitivity of a triple-camera SPECT system and reduce statistical noise in reconstructed images using a combination of converging collimators. The reason for combining collimators is to ensure both high sensitivity and sufficient sampling without trading off spatial resolution. METHODS: A high-sensitivity half-cone-beam (HCB) collimator, designed specifically for brain imaging, was combined with other collimators and compared with conventional parallel-beam and fanbeam circular orbit acquisitions. For comparison, previously studied HCB collimation with a circle-and-helix data acquisition trajectory was also included in this study. Simulations of the Hoffman 3-dimensional brain phantom were performed to calculate the efficiencies of collimators and their combinations and to quantitatively evaluate reconstruction bias, statistical noise, and signal-to-noise ratios in the reconstructed images. Experimental brain phantom data were also acquired and compared for different acquisition types. Finally, a patient brain scan was obtained with a combination of HCB and fanbeam collimators and compared with a triple-fanbeam circular orbit acquisition. RESULTS: A combination of 2 HCB collimators and 1 fanbeam collimator, compared with a triple-fanbeam collimator, can increase the photon detection efficiency by 27% and by more than a factor of 2, compared with triple-parallel-hole collimation, with equal spatial resolution measured on the axis of rotation. Quantitative analysis of reconstruction bias and visual analysis of the images showed no signs of sampling artifacts. Reconstructed images in the simulations, experimental brain phantom, and patient brain scans showed improved quality with this collimator combination due to increased sensitivity and reduced noise. Lesion visibility was also improved, as confirmed by signal-to-noise ratios. Alternatively, triple-HCB circle-and-helix acquisition has also shown competitive results, with a slight disadvantage in axial sampling and implementation procedure. CONCLUSION: Combined HCB and fanbeam collimation is a promising approach for high-sensitivity brain SPECT.

Increasing uptake time in FDG-PET: standardized uptake values in normal tissues at 1 versus 3 h.

OBJECTIVE: Positron emission tomography (PET) imaging at more than 1 h after 2-deoxy-2-[(18)F]fluoro-D: -glucose (FDG) administration may result in less blood pool activity and possibly decreased normal FDG uptake in tissues such as liver. Lower normal background activity could be an important component of improved image contrast on delayed imaging. Increasing FDG uptake in normal organs, however, may mitigate the beneficial effects of blood pool clearance. The purpose of this study is to determine the normal tissue and blood pool FDG uptake at 1 and 3 h after injection. SUBJECTS AND METHODS: Ninety-nine patients with known or suspected malignancy referred for FDG-PET-computed tomography (CT) were retrospectively evaluated. PET imaging was performed at either 1 h (60 +/- 15 min; n = 50) or at 3 h (180 +/- 15 min; n = 49) after FDG administration. Normal tissue FDG uptake without involvement by malignancy or influenced by artifact (misregistration, "brown fat," focal muscle uptake, focal atherosclerotic disease) was confirmed by inspection of both the PET and CT scans. Aortic blood pool, adipose tissue, bone marrow, cerebellum, liver, lungs, muscle, and spleen were quantitatively evaluated by CT-guided region of interest analysis in three contiguous slices. Mean standardized uptake values (SUVs) were analyzed using one-way analysis of variance. RESULTS: Mean SUVs on the 3- versus 1-h images were significantly lower for aortic blood pool 13% (p < 0.0001) and adipose tissue 20% (p < 0.008). FDG uptake showed significant increases at 3 h compared to 1-h imaging in the cerebellum 40% (p < 0.0001), bone marrow 25% (p = 0.003), muscle 21% (p = 0.0004), and spleen 13% (p = 0.01). The liver and lung showed no significant differences (1%, p = 0.85; -2%, p = 0.62, respectively). CONCLUSIONS: On FDG imaging at 3 h compared to 1 h, significant changes were apparent, but the magnitude of changes was modest overall. Three-hour delayed imaging demonstrated significantly lower aortic blood pool and adipose tissue activity and significantly higher cerebellum, muscle, spleen, and bone marrow activity. Hepatic and lung activities were not significantly different. These results suggest that previously reported improvements in tumor image contrast with delayed imaging may be primarily due to cumulative FDG uptake within the tumor rather than reduction in normal background activity.

Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors.

The purpose of this study is to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and intracerebral distribution of a recombinant toxin (TP-38) targeting the epidermal growth factor receptor in patients with recurrent malignant brain tumors using the intracerebral infusion technique of convection-enhanced delivery (CED). Twenty patients were enrolled and stratified for dose escalation by the presence of residual tumor from 25 to 100 ng/ml in a 40-ml infusion volume. In the last eight patients, coinfusion of (123)I-albumin was performed to monitor distribution within the brain. The MTD was not reached in this study. Dose escalation was stopped at 100 ng/ml due to inconsistent drug delivery as evidenced by imaging the coinfused (123)I-albumin. Two DLTs were seen, and both were neurologic. Median survival after TP-38 was 28 weeks (95% confidence interval, 26.5-102.8). Of 15 patients treated with residual disease, two (13.3%) demonstrated radiographic responses, including one patient with glioblastoma multiforme who had a nearly complete response and remains alive >260 weeks after therapy. Coinfusion of (123)I-albumin demonstrated that high concentrations of the infusate could be delivered >4 cm from the catheter tip. However, only 3 of 16 (19%) catheters produced intraparenchymal infusate distribution, while the majority leaked infusate into the cerebrospinal fluid spaces. Intracerebral CED of TP-38 was well tolerated and produced some durable radiographic responses at doses

A pilot study: 131I-antitenascin monoclonal antibody 81c6 to deliver a 44-Gy resection cavity boost.

The purpose of this study was to determine the feasibility and assess the efficacy and toxicity, among newly diagnosed malignant glioma patients, of administering (131)I-labeled murine antitenascin monoclonal antibody 81C6 ((131)I-81C6) into a surgically created resection cavity (SCRC) to achieve a patient-specific, 44-Gy boost to the 2-cm SCRC margin. A radioactivity dose of (131)I-81C6 calculated to achieve a 44-Gy boost to the SCRC was administered, followed by conventional external beam radiotherapy (XRT) and chemotherapy. Twenty-one patients were enrolled in the study: 16 with glioblastoma multiforme (GBM) and 5 with anaplastic astrocytoma. Twenty patients received the targeted 44-Gy boost (+/-10%) to the SCRC. Attributable toxicity was mild and limited to reversible grade 3 neutropenia or thrombocytopenia (n = 3; 14%), CNS wound infections (n = 3; 14%), and headache (n = 2; 10%). With a median follow-up of 151 weeks, median overall survival times for all patients and those with GBM are 96.6 and 90.6 weeks, respectively; 87% of GBM patients are alive at 1 year. It is feasible to consistently achieve a 44-Gy boost dose to the SCRC margin with patient-specific dosing of (131)I-81C6. Our study regimen ((131)I-81C6 + XRT + temozolomide) was well tolerated and had encouraging survival. To determine if selection of good-prognosis patients affects outcome associated with this approach, the U.S. Food and Drug Administration has approved a trial randomizing newly diagnosed GBM patients to either our study regimen or standard XRT plus temozolomide.

Relationship between cancer type and impact of PET and PET/CT on intended management: findings of the national oncologic PET registry.

UNLABELLED: We previously reported aggregate data showing that PET was associated with a change in intended management for over one third of patients participating in the National Oncologic PET Registry (NOPR). Here, we present results for specific cancer types and indications for testing. METHODS: The NOPR collected questionnaire data from referring physicians on intended management before and after PET. Data were available from 40,863 PET studies done at 1,368 centers. The impact of PET was assessed for 18 cancer types in patients with pathologically confirmed cancer by type and indication for testing (initial staging, restaging, or detection of suspected recurrence), other than treatment monitoring. RESULTS: When intended management was classified as treatment or nontreatment, physicians changed their intended management for 38.0% of cases (95% confidence interval = 37.6%-38.5%). The frequencies of changes in management ranged from 48.7% for myeloma to 31.4% for nonmelanoma skin cancer. Comparisons across testing indications revealed that only in multiple myeloma did PET have a consistently greater impact on intended management. When the intended management plan before PET was treatment, a change in the intent of treatment (curative vs. palliative) or a major change in the modality of treatment occurred at similar frequencies across different cancer types. CONCLUSION: The impact of PET on physicians' intended management for patients with known cancer was consistent across cancer types.

Clinical experience with alpha-particle emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6.

UNLABELLED: alpha-Particle-emitting radionuclides, such as (211)At, with a 7.2-h half-life, may be optimally suited for the molecularly targeted radiotherapy of strategically sensitive tumor sites, such as those in the central nervous system. Because of the much shorter range and more potent cytotoxicity of alpha-particles than of beta-particles, (211)At-labeled agents may be ideal for the eradication of tumor cells remaining after surgical debulking of malignant brain tumors. The main goal of this study was to investigate the feasibility and safety of this approach in patients with recurrent malignant brain tumors. METHODS: Chimeric antitenascin monoclonal antibody 81C6 (ch81C6) (10 mg) was labeled with 71-347 MBq of (211)At by use of N-succinimidyl 3-[(211)At]astatobenzoate. Eighteen patients were treated with (211)At-labeled ch81C6 ((211)At-ch81C6) administered into a surgically created resection cavity (SCRC) and then with salvage chemotherapy. Serial gamma-camera imaging and blood sampling over 24 h were performed. RESULTS: A total of 96.7% +/- 3.6% (mean +/- SD) of (211)At decays occurred in the SCRC, and the mean blood-pool percentage injected dose was < or = 0.3. No patient experienced dose-limiting toxicity, and the maximum tolerated dose was not identified. Six patients experienced grade 2 neurotoxicity within 6 wk of (211)At-ch81C6 administration; this neurotoxicity resolved fully in all but 1 patient. No toxicities of grade 3 or higher were attributable to the treatment. No patient required repeat surgery for radionecrosis. The median survival times for all patients, those with glioblastoma multiforme, and those with anaplastic astrocytoma or oligodendroglioma were 54, 52, and 116 wk, respectively. CONCLUSION: This study provides proof of concept for regional targeted radiotherapy with (211)At-labeled molecules in oncology. Specifically, the regional administration of (211)At-ch81C6 is feasible, safe, and associated with a promising antitumor benefit in patients with malignant central nervous system tumors.

A comparison of the diagnostic accuracy of 18F-FDG PET and CT in the characterization of solitary pulmonary nodules.

UNLABELLED: CT and PET are widely used to characterize solitary pulmonary nodules (SPNs). However, most CT accuracy studies have been performed with outdated technology and methods, and previous PET studies have been limited by small sample sizes and incomplete masking. Our objective was to compare CT and PET accuracy in veterans with SPN. METHODS: Between January 1999 and June 2001, we recruited 532 participants with SPNs newly diagnosed on radiography and untreated. The SPNs were 7-30 mm. All patients underwent (18)F-FDG PET and CT. A masked panel of 3 PET and 3 CT experts rated the studies on a 5-point scale. SPN tissue diagnosis or 2-y follow-up established the final diagnosis. RESULTS: A definitive diagnosis was established for 344 participants. The prevalence of malignancy was 53%. The average size was 16 mm. Likelihood ratios (LRs) for PET and CT results for combined ratings of either definitely benign (33% and 9% of patients, respectively) or probably benign (27% and 12%) were 0.10 and 0.11, respectively. LRs for PET and CT results for combined ratings of indeterminate (1% and 25%), probably malignant (21% and 39%), or definitely malignant (35% and 15%) were 5.18 and 1.61, respectively. Area under the receiver operating characteristic curve was 0.93 (95% confidence interval, 0.90-0.95) for PET and 0.82 (95% confidence interval, 0.77-0.86) for CT (P < 0.0001 for the difference). PET inter- and intraobserver reliability was superior to CT. CONCLUSION: Definitely and probably benign results on PET and CT strongly predict benign SPN. However, such results were 3 times more common with PET. Definitely malignant results on PET were much more predictive of malignancy than were these results on CT. A malignant final diagnosis was approximately 10 times more likely than a benign final diagnosis in participants with PET results rated definitely malignant.

Recommendations on the use of 18F-FDG PET in oncology.

UNLABELLED: The rationale was to develop recommendations on the use of (18)F-FDG PET in breast, colorectal, esophageal, head and neck, lung, pancreatic, and thyroid cancer; lymphoma, melanoma, and sarcoma; and unknown primary tumor. Outcomes of interest included the use of (18)F-FDG PET for diagnosing, staging, and detecting the recurrence or progression of cancer. METHODS: A search was performed to identify all published randomized controlled trials and systematic reviews in the literature. An additional search was performed to identify relevant unpublished systematic reviews. These publications comprised both retrospective and prospective studies of varied methodologic quality. The anticipated consequences of false-positive and false-negative tests when evaluating clinical usefulness, and the impact of (18)F-FDG PET on the management of cancer patients, were also reviewed. RESULTS AND CONCLUSION: (18)F-FDG PET should be used as an imaging tool additional to conventional radiologic methods such as CT or MRI; any positive finding that could lead to a clinically significant change in patient management should be confirmed by subsequent histopathologic examination because of the risk of false-positive results. (18)F-FDG PET should be used in the appropriate clinical setting for the diagnosis of head and neck, lung, or pancreatic cancer and for unknown primary tumor. PET is also indicated for staging of breast, colon, esophageal, head and neck, and lung cancer and of lymphoma and melanoma. In addition, (18)F-FDG PET should be used to detect recurrence of breast, colorectal, head and neck, or thyroid cancer and of lymphoma.

Quantitative effects of contrast enhanced CT attenuation correction on PET SUV measurements.

PURPOSE: The presence of contrast materials on computed tomography (CT) images can cause problems in the attenuation correction of positron emission tomography (PET) images. These are because of errors converting the CT attenuation of contrast to 511-keV attenuation and by the change in tissue enhancement over the duration of the PET emission scan. Newer CT-based attenuation correction (CTAC) algorithms have been developed to reduce these errors. METHODS: To evaluate the effectiveness of the modified CTAC technique, we performed a retrospective analysis on 20 patients, comparing PET images using unenhanced and contrast-enhanced CT scans for attenuation correction. A phantom study was performed to simulate the effects of contrast on radiotracer concentration measurements. RESULTS: There was a maximum difference in calculated radiotracer concentrations of 5.9% within the retrospective data and 7% within the phantom data. CONCLUSION: Using a CTAC algorithm that de-emphasizes high-density areas, contrast-enhanced CT can be used for attenuation mapping without significant errors in quantitation.

Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions.

Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain. Despite the promise of CED, clinical trials have demonstrated that target-tissue anatomy and patient-specific physiology play a major role in drug distribution using this technique. In this study, we retrospectively tested the ability of a software algorithm using MR diffusion tensor imaging to predict patient-specific drug distributions by CED. A tumor-targeted cytotoxin, cintredekin besudotox (interleukin 13-PE38QQR), was coinfused with iodine 123-labeled human serum albumin (123I-HSA), in patients with recurrent malignant gliomas. The spatial distribution of 123I-HSA was then compared to a drug distribution simulation provided by the software algorithm. The algorithm had a high sensitivity (71.4%) and specificity (100%) for identifying the high proportion (7 of 14) of catheter trajectories that failed to deliver drug into the desired anatomical region (p = 0.021). This usually occurred when catheter trajectories crossed deep sulci, resulting in leak of the infusate into the subarachnoid cerebrospinal fluid space. The mean concordance of the volume of distribution at the 50% isodose level between the actual 123I-HSA distribution and simulation was 65.75% (95% confidence interval [CI], 52.0%-79.5%), and the mean maximal inplane deviation was less than 8.5 mm (95% CI, 4.0-13.0 mm). The use of this simulation algorithm was considered clinically useful in 84.6% of catheters. Routine use of this algorithm, and its further developments, should improve prospective selection of catheter trajectories, and thereby improve the efficacy of drugs delivered by this promising technique.

Regional brain activity correlates of nicotine dependence.

Fifteen smokers participated in a study investigating brain correlates of nicotine dependence. Dependence was reduced by having subjects switch to denicotinized cigarettes for 2 weeks while wearing nicotine skin patches. Positron emission tomography (PET) scans assessed regional cerebral metabolic rate for glucose (rCMRglc) after overnight nicotine abstinence on three occasions: (1) at baseline; (2) after 2 weeks of exposure to denicotinized cigarettes+nicotine patches; and (3) 2 weeks after returning to smoking the usual brands of cigarettes. Craving for cigarettes and scores on the Fagerström Test of Nicotine Dependence (FTND) questionnaire decreased at the second session relative to the first and last sessions. Regional brain metabolic activity (normalized to whole brain values) at session 2 also showed a significant decrease in the right hemisphere anterior cingulate cortex. Exploratory post hoc analyses showed that the change in craving across sessions was negatively correlated with the change in rCMRglc in several structures within the brain reward system, including the ventral striatum, orbitofrontal cortex and pons. The between-session difference in thalamus activity (right hemisphere) was positively correlated with the difference in FTND scores. Correlational analyses also revealed that reported smoking for calming effects was associated with a decrease (at session 2) in thalamus activity (bilaterally) and with an increase in amygdala activity (left hemisphere). Reported smoking to enhance pleasurable relaxation was associated with an increase in metabolic activity of the dorsal striatum (caudate, putamen) at session 2. These findings suggest that reversible changes in regional brain metabolic activity occur in conjunction with alterations in nicotine dependence. The results also highlight the likely role of thalamic gating processes as well as striatal reward and corticolimbic regulatory pathways in the maintenance of cigarette addiction.

The National Oncologic PET Registry (NOPR): design and analysis plan.

UNLABELLED: The Centers for Medicare and Medicaid Services (CMS) has provided a mechanism for expanded coverage of selected promising technologies under its "coverage with evidence development (CED)" policy. The National Oncologic PET Registry (NOPR) was designed to address the CED requirements for collection of clinical and demographic data to allow for CMS coverage of PET for previously noncovered cancer types and indications. The NOPR opened in May 2006. This report reviews the NOPR's data collection and analysis plan. METHODS: NOPR is a nationwide prospective internet-based registry. All PET facilities that are participating providers in the Medicare program may enroll in NOPR. The PET facility is responsible for collecting and entering patient data into the NOPR database through a Web application at: (http://www.cancerPETregistry.org/). Data are collected from the requesting physician on Pre-PET and Post-PET forms. The primary research goal is to assess the effect of PET on referring physicians' plans of intended patient management across the spectrum of expanded cancer indications (diagnosis, staging, restaging, suspected recurrence, and treatment monitoring). The NOPR investigators will have access to data only on cases in which both the patient and the referring physician have consented to allow their data to be used for research. Data will be analyzed and compared in aggregate for all cancers by category (e.g., staging) and then for specific high-impact types and indications (e.g., staging of pancreatic cancer) when 200 patients have been accrued to a specific combination or after the NOPR has been operational for 1 y. CONCLUSION: The NOPR will allow an accurate assessment of the impact of PET on intended patient management across a wide spectrum of cancer indications.

Practical approach to diagnostic CT combined with PET.

OBJECTIVE: Protocols for PET/CT are not yet standardized. In particular, image quality, utilization, and reporting of the findings of the CT component of PET/CT can vary widely, making it complicated for physicians to request the appropriate information. In an effort to address this problem, we describe a set of four PET/CT protocols that satisfy a broad range of clinical needs among oncology patients. Current technology allows acquisition of diagnostic-quality CT scans as part of PET/CT examinations, and referring physicians are given the option of requesting formal interpretation of the CT findings. In this case, the PET and CT images are interpreted by the corresponding specialists, and equivocal or discordant findings are adjudicated through joint review of the PET/CT images. CONCLUSIONS: The menu of PET/CT imaging protocols has gained wide acceptance by our referring physicians and have been used successfully in more than 6,000 PET/CT studies. Newer PET/CT protocols will be developed as technology advances. Continued collaboration among oncologists, CT specialists, and nuclear medicine specialists is essential for deriving the maximum clinical benefit from combined PET/CT. Standardization of imaging protocols will become increasingly important as multiple-institution trials are developed for evaluation of present and future applications of PET/CT.

Induction of hyperintense signal on T2-weighted MR images correlates with infusion distribution from intracerebral convection-enhanced delivery of a tumor-targeted cytotoxin.

OBJECTIVE: Convection-enhanced delivery is a promising approach to intracerebral drug delivery in which a fluid pressure gradient is used to infuse therapeutic macromolecules through an indwelling catheter into the interstitial spaces of the brain. Our purpose was to test the hypothesis that hyperintense signal changes on T2-weighted images produced by such infusions can be used to track drug distribution. SUBJECTS AND METHODS: Seven adults with recurrent malignant glioma underwent concurrent intracerebral infusions of the tumor-targeted cytotoxin cintredekin besudotox and 123I-labeled human serum albumin. The agents were administered through a total of 18 catheters among the seven patients. Adequacy of distribution of drug was determined by evidence of distribution of 123I-labeled human serum albumin on SPECT images coregistered with MR images. Qualitative analysis was performed by three blinded observers. Quantitative analysis also was performed. RESULTS: Infusions into 12 catheters produced intraparenchymal distribution as seen on SPECT images, but infusions into six catheters did not. At qualitative assessment of signal changes on MR images, reviewers correctly predicted which catheters would produce extraparenchymal distribution and which catheters would produce parenchymal distribution. Of the 12 infusions that produced intraparenchymal distribution, four catheters had been placed in regions of relatively normal signal intensity and produced regions of newly increased signal intensity, the volume of which highly correlated with the volume and geometry of distribution on SPECT (r2 = 0.9502). Eight infusions that produced intraparenchymal distribution were performed in regions of preexisting hyperintense signal. In these brains, additional signal changes were always produced, but quantitative correlations between areas of newly increased signal intensity and the volume and geometry of distribution on SPECT could not be established. CONCLUSION: Convection-enhanced infusions frequently do not provide intraparenchymal drug distribution, and these failures can be identified with MRI soon after infusion. When infusions are performed into regions of normal signal intensity, development of hyperintense signal change strongly correlates with the volume and geometry of distribution of infusate.

The National Oncologic PET Registry: expanded medicare coverage for PET under coverage with evidence development.

OBJECTIVE: The purpose of this article is to review the recent expansion of Medicare coverage for 18F-FDG PET for certain cancer indications under the Centers for Medicare & Medicaid Services' new Coverage with Evidence Development (CED) policy and to describe the specific operational mechanics of the National Oncologic PET Registry (NOPR). CONCLUSION: The NOPR will make possible a more accurate assessment of the actual influence of PET on patient management across a wide spectrum of cancer indications. By linking access to PET for virtually all Medicare beneficiaries to the collection of clinically valuable evidence, the NOPR represents the cutting edge of the CED approach.

Novel human IgG2b/murine chimeric antitenascin monoclonal antibody construct radiolabeled with 131I and administered into the surgically created resection cavity of patients with malignant glioma: phase I trial results.

UNLABELLED: Results from animal experiments have shown that human IgG2/mouse chimeric antitenascin 81C6 (ch81C6) monoclonal antibody exhibited higher tumor accumulation and enhanced stability compared with its murine parent. Our objective was to determine the effect of these differences on the maximum tolerated dose (MTD), pharmacokinetics, dosimetry, and antitumor activity of (131)I-ch81C6 administered into the surgically created resection cavity (SCRC) of malignant glioma patients. METHODS: In this phase I trial, eligible patients received a single injection of (131)I-ch81C6 administered through a Rickham catheter into the SCRC. Patients were stratified as newly diagnosed and untreated (stratum A), newly diagnosed after external beam radiotherapy (XRT) (stratum B), and recurrent (stratum C). (131)I-ch81C6 was administered either before (stratum A) or after (stratum B) conventional XRT for newly diagnosed patients. In addition, chemotherapy was prescribed for all patients after (131)I-ch81C6 administration. Dose escalation was performed independently for each stratum. Patients were observed for toxicity and response until death or progressive disease. RESULTS: We treated 47 patients with (131)I-ch81C6 doses up to 4.44 GBq (120 mCi), including 35 with newly diagnosed tumors (strata A and B) and 12 with recurrent disease (stratum C). Dose-limiting hematologic toxicity defined the MTD to be 2.96 GBq (80 mCi) for all patients, regardless of treatment strata. Neurologic dose-limiting toxicity developed in 3 patients; however, none required further surgery to debulk radiation necrosis. Median survival was 88.6 wk and 65.0 wk for newly diagnosed and recurrent patients, respectively. CONCLUSION: The MTD of (131)I-ch81C6 is 2.96 GBq (80 mCi) because of dose-limiting hematologic toxicity. Although encouraging survival was observed, (131)I-ch81C6 was associated with greater hematologic toxicity, probably due to the enhanced stability of the IgG2 construct, than previously observed with (131)I-murine 81C6.

3'-Deoxy-3'-[F-18]fluorothymidine positron emission tomography in patients with recurrent glioblastoma multiforme: comparison with Gd-DTPA enhanced magnetic resonance imaging.

INTRODUCTION: The accumulation of 3'-deoxy-3'-[F-18]fluorothymidine (FLT) on positron emission tomography (PET) images in patients with glioblastoma multiforme was evaluated and correlated with gadopentetate dimeglumine (Gd-DTPA) enhancement in magnetic resonance images (MRIs). METHODS: FLT studies in 10 patients with recurrent glioblastoma multiforme were retrospectively investigated. Dynamic emission data were acquired for 60 minutes immediately after injection of FLT. The standardized uptake value (SUV) for tumor and reference tissue (contralateral hemisphere and ipsilateral cerebellum) was calculated. The volumes of the metabolically active part of the tumor (V (PET)) and that of the Gd-DTPA enhancing part of the tumor (V (MR)) were calculated. RESULTS: FLT uptake in tumors peaked before 5 minutes and sometimes as early as 0.5 minutes, and reached a constant level at approximately 10 minutes after injection. The reference tissue time-activity curves had an early peak and reached a constant low background level. All tumors had increased FLT uptake and showed Gd-DTPA enhancement. The SUV in tumor was significantly higher than that in the reference tissue (P<0.0001). A significant correlation between V (PET) and V (MR) was found (P<0.0001) although there was a difference in the areas of Gd-DTPA enhancement and FLT uptake. CONCLUSION: These preliminary results indicate that FLT-PET may be useful for the detection of recurrent glioblastoma multiforme. Our data in a relatively small patient population do not support a clear-cut relationship between FLT accumulation and Gd-DTPA enhancement. Further pathologic correlation will determine if it can be used for detecting recurrent tumoral disease.