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Biomedical subjects

Johannes Czernin

Publications and source records attributed to Johannes Czernin.

At least 19 recordsLinked to original sources
PubMed2007

Evaluation of suspected local recurrence in head and neck cancer: a comparison between PET and PET/CT for biopsy proven lesions.

BACKGROUND: (18)F-FDG PET has a high accuracy for re-staging of head and neck cancer. The purpose of this study was to determine whether the diagnostic accuracy can be further improved with integrated PET/CT. MATERIALS AND METHODS: Forty-nine patients with a mean age of 59+/-18 years were studied retrospectively. Histo-pathological verification was available either from complete tumor resection with or without lymph node dissection (n=27) or direct endoscopic biopsy (n=16) or ultrasound guided biopsy (n=6). Two reviewers blinded to the pathological findings read all PET images in consensus. An experienced radiologist was added for the interpretation of the PET/CT images. RESULTS: Tissue verification was available for 110 lesions in 49 patients. Sixty-seven lesions (61%) were biopsy positive and 43 (39%) were negative for malignant disease. PET and PET/CT showed an overall accuracy for cancer detection of 84 and 88% (p=0.06), respectively. Sensitivity and specificity for PET were 78 and 93% versus 84 (p=NS) and 95% (p=NS) with PET/CT. A patient-by-patient analysis yielded a sensitivity, specificity and accuracy for PET of 80, 56 and 76%, compared to 88% (p=NS), 78% (p=NS) and 86% (p=0.06) for PET/CT. CONCLUSION: The results of this study indicate that PET/CT does not significantly improve the detection of recurrence of head and neck cancer. However, a trend towards improved accuracy was observed (p=0.06).

Adult↗
PubMed2007

Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006.

PET/CT with 18F-FDG is increasingly being used for staging, restaging, and treatment monitoring for cancer patients. CT is still frequently used only for attenuation correction and lesion localization. However, increasing sales of high-end scanners that combine PET with 64-detector CT strongly suggest that the field is moving toward a comprehensive concept, whereby diagnostic CT studies during intravenous contrast material application are combined with the highest-quality PET studies. At many institutions, in-line PET/CT has replaced separately acquired PET and CT examinations for many oncologic indications. This replacement has occurred despite the fact that only a relatively small number of well-designed prospective studies have verified imaging findings against the gold standard of histopathologic tissue evaluation. However, a large number of studies have used acceptable reference standards, such as pathology, imaging, and other clinical follow-up findings, for validating PET/CT findings. From these data, we believe, has emerged reliable evidence in support of the notion that PET/CT offers diagnostic advantages over its individual components for the major cancers.

Clinical Trials as Topic↗
PubMed2006

Monitoring tumor glucose utilization by positron emission tomography for the prediction of treatment response to epidermal growth factor receptor kinase inhibitors.

PURPOSE: The mechanisms underlying the sensitivity of non-small cell lung cancer to epidermal growth factor receptor (EGFR) kinase inhibitors are complex, and there are no established markers to accurately predict treatment outcome in individual patients. EXPERIMENTAL DESIGN: We investigated whether tumors responding to EGFR inhibitors can be identified by measuring treatment-induced changes in glucose utilization by positron emission tomography with the glucose analogue fluorodeoxyglucose (FDG-PET). We studied a panel of cell lines with a spectrum of sensitivity to EGFR kinase inhibitors. After incubation with the EGFR kinase inhibitor gefitinib for various time points, FDG uptake, glucose transport rates, and hexokinase activity were determined. FDG uptake in vivo was assessed by microPET imaging of tumor xenografts in mice. RESULTS: In gefitinib-sensitive cell lines, there was a dramatic decrease in FDG uptake as early as 2 hours after treatment. Immunoblots showed the translocation of glucose transporters (GLUT3) from the plasma membrane to the cytosol; glucose transport rates were reduced 2.6-fold at this time. There was also a modest reduction of hexokinase activity. These metabolic alterations preceded changes in cell cycle distribution, thymidine uptake, and apoptosis. MicroPET studies showed an up to 55% decrease of tumor FDG uptake in sensitive xenografts within 48 hours. In contrast, gefitinib-resistant cells exhibited no measurable changes in FDG uptake, either in cell culture or in vivo. CONCLUSION: Glucose metabolic activity closely reflects response to gefitinib therapy. FDG-PET may be a valuable clinical predictor, early in the course of treatment, for therapeutic responses to EGFR kinase inhibitors.

Animals↗
PubMed2006

Molecular imaging in the development of cancer therapeutics.

Researchers have made great progress in defining genetic and molecular alterations that contribute to cancer. New therapeutic targets have been identified and targeted therapeutic agents have been developed, but our ability to evaluate potential drugs has not kept pace. Molecular imaging technologies that monitor biological processes and/or measure levels of targeted macromolecules can contribute significantly to preclinical and clinical drug evaluation. This article describes the drug discovery process, economic problems facing drug discovery and development, and successes and failures in this realm. We briefly describe the available molecular imaging tools, with emphasis on positron emission tomography. We discuss biological processes that are altered in tumors and can be measured by molecular imaging; examples include gene expression, signal transduction, tumor cell metabolism, proliferation, apoptosis, hypoxia, and angiogenesis. We conclude with a proposal to integrate molecular imaging into the drug development process.

Drug Approval↗
PubMed2006

Evaluation of thoracic tumors with 18F-fluorothymidine and 18F-fluorodeoxyglucose-positron emission tomography.

STUDY OBJECTIVES: 18F-fluorodeoxyglucose (FDG) is the most widely used positron emission tomography (PET) imaging probe used for the diagnosis, staging, restaging, and monitoring therapy response of cancer. However, its specificity is less than ideal. A new molecular imaging probe (18F-deoxyfluorothymidine [FLT]) has been developed that might afford more specific tumor imaging. The aims of this study were as follows: (1) to compare the use of FDG-PET and FLT-PET for tumor staging, (2) to compare the degree of FDG and FLT uptake in lung lesions, and (3) to determine the correlation between PET uptake intensity and tumor cell proliferation. DESIGN: FDG-PET and FLT-PET scans were performed in 11 patients with solitary pulmonary nodules and another 11 patients with known non-small cell lung cancer (NSCLC). Tracer uptake was assessed quantitatively by standardized uptake values (SUVs). Histologic evaluation of tissue samples obtained from biopsy specimens or surgical resections served as the "gold standard." Tumor cell proliferation was assessed by Ki-67 staining. RESULTS: Pathology verification was available from 99 tissue samples in the 22 patients (29 pulmonary lesions, 66 lymph node stations, and 4 extrapulmonary lesions). Thirty-three samples (33.3%) were positive for tumor tissue (22 pulmonary, 9 lymph node stations, and 2 extrapulmonary). FDG-PET findings were false-positive in three pulmonary lesions, while FLT-PET findings were false-positive in one lesion. There were two false-negative findings by FDG-PET and six false-negative findings by FLT-PET. FDG uptake of the malignant lesions was significantly higher than FLT (maximum SUV, 3.1 +/- 2.6 vs 1.6 +/- 1.2 [mean +/- SD]; p < 0.05). A significant correlation was observed between FLT uptake of pulmonary lesions and Ki-67 labeling index (r = 0.60, p = 0.02) but not for FDG uptake (r = 0.27, p = not significant). CONCLUSIONS: Compared to FDG-PET, detection of primary and metastatic NSCLC by FLT-PET is limited by the relatively low FLT uptake of the tumor tissue. Thus, FLT-PET is unlikely to provide more accurate staging information or better characterization of pulmonary nodules than FDG-PET. Nevertheless, the correlation between FLT uptake and cellular proliferation suggests that future studies should evaluate the use of FLT-PET for monitoring treatment with cytostatic anticancer drugs.

Aged↗
PubMed2006

Standard PET/CT of the chest during shallow breathing is inadequate for comprehensive staging of lung cancer.

UNLABELLED: The incidence of malignancy associated with subcentimeter pulmonary nodules (micronodules) in patients with malignant disease has been reported to be as high as 58%. Thus, detection of small lung nodules is important for appropriate staging of lung cancer. Because of respiratory motion, small parenchymal lung lesions can be missed on CT acquired during shallow breathing. Micronodules are usually too small to be characterized reliably with 18F-FDG PET. We aimed to determine the incidence of missed pulmonary micronodules on PET/CT studies acquired during shallow breathing. METHODS: The study included 142 consecutive cancer patients (62 male and 80 female; mean age, 54 y) who underwent whole-body PET/CT during shallow breathing and breath-hold CT of the chest during maximal inspiration. CT findings were reviewed independently, and noncalcified nodules missed on the shallow-breathing scan were evaluated for size, location, and metabolic activity. RESULTS: Breath-hold chest CT detected an additional 125 parenchymal lung nodules (mean size, 3.4 +/- 1.6 mm; range, 1-9 mm) in 48 (34%) of the 142 patients. In these patients, 3 nodules, on average, were missed during shallow breathing. In 18 patients (13%), micronodules were identified exclusively on breath-hold images. None of the missed nodules demonstrated 18F-FDG uptake. CONCLUSION: Acquisition of standard PET/CT chest images during shallow breathing is inadequate for comprehensive cancer staging.

Artifacts↗
PubMed2006

18F-FDOPA PET imaging of brain tumors: comparison study with 18F-FDG PET and evaluation of diagnostic accuracy.

UNLABELLED: We evaluated the amino acid and glucose metabolism of brain tumors by using PET with 3,4-dihydroxy-6-(18)F-fluoro-l-phenylalanine ((18)F-FDOPA) and (18)F-FDG. METHODS: Eighty-one patients undergoing evaluation for brain tumors were studied. Initially, 30 patients underwent PET with (18)F-FDOPA and (18)F-FDG within the same week. Tracer kinetics in normal brain and tumor tissues were estimated. PET uptake was quantified by use of standardized uptake values and the ratio of tumor uptake to normal hemispheric tissue uptake (T/N). In addition, PET uptake with (18)F-FDOPA was quantified by use of ratios of tumor uptake to striatum uptake (T/S) and of tumor uptake to white matter uptake. The accuracies of (18)F-FDOPA and (18)F-FDG PET were determined by comparing imaging data with histologic findings and findings of clinical follow-up of up to 31 mo (mean, 20 mo). To further validate the accuracy of (18)F-FDOPA PET, (18)F-FDOPA PET was performed with an additional 51 patients undergoing brain tumor evaluation. RESULTS: Tracer uptake in tumors on (18)F-FDOPA scans was rapid, peaking at approximately 15 min after intravenous injection. Tumor uptake could be distinguished from that of the striatum by the difference in peak times. Both high-grade and low-grade tumors were well visualized with (18)F-FDOPA. The sensitivity for identifying tumors was substantially higher with (18)F-FDOPA PET than with (18)F-FDG PET at comparable specificities, as determined by simple visual inspection, especially for the assessment of low-grade tumors. Using receiver-operating-characteristic curve analysis, we found the optimal threshold for (18)F-FDOPA to be a T/S of greater than 1.0 (sensitivity, 96%; specificity, 100%) or a T/N of greater than 1.3 (sensitivity, 96%; specificity, 86%). The high diagnostic accuracy of (18)F-FDOPA PET at these thresholds was confirmed with the additional 51 patients (a total of 81 patients: sensitivity, 98%; specificity, 86%; positive predictive value, 95%; negative predictive value, 95%). No significant difference in tumor uptake on (18)F-FDOPA scans was seen between low-grade and high-grade tumors (P = 0.40) or between contrast-enhancing and nonenhancing tumors (P = 0.97). Radiation necrosis was generally distinguishable from tumors on (18)F-FDOPA scans (P < 0.00001). CONCLUSION: (18)F-FDOPA PET was more accurate than (18)F-FDG PET for imaging of low-grade tumors and evaluating recurrent tumors. (18)F-FDOPA PET may prove especially useful for imaging of recurrent low-grade tumors and for distinguishing tumor recurrence from radiation necrosis.

Adult↗
PubMed2006

Impact of animal handling on the results of 18F-FDG PET studies in mice.

UNLABELLED: Small-animal PET scanning with (18)F-FDG is increasingly used in murine models of human diseases. However, the impact of dietary conditions, mode of anesthesia, and ambient temperature on the biodistribution of (18)F-FDG in mice has not been systematically studied so far. The aim of this study was to determine how these factors affect assessment of tumor glucose use by (18)F-FDG PET and to develop an imaging protocol that optimizes visualization of tumor xenografts. METHODS: Groups of severe combined immunodeficient (SCID) mice were first imaged by microPET with free access to food, at room temperature (20 degrees C), and no anesthesia during the uptake period (reference condition). Subsequently, the impact of (a) fasting for 8-12 h, (b) warming the animals with a heating pad (30 degrees C), and (c) general anesthesia using isoflurane or ketamine/xylazine on the (18)F-FDG biodistribution was evaluated. Subcutaneously implanted human A431 epidermoid carcinoma and U251 glioblastoma cells served as tumor models. RESULTS: Depending on the study conditions, (18)F-FDG uptake by normal tissues varied 3-fold for skeletal muscle, 13-fold for brown adipose tissue, and 15-fold for myocardium. Warming and fasting significantly reduced the intense (18)F-FDG uptake by brown adipose tissue observed under the reference condition and markedly improved visualization of tumor xenografts. Although tumor (18)F-FDG uptake was not above background activity under the reference condition, tumors demonstrated marked focal (18)F-FDG uptake in warmed and fasted animals. Quantitatively, tumor (18)F-FDG uptake increased 4-fold and tumor-to-organ ratios were increased up to 17-fold. Ketamine/xylazine anesthesia caused marked hyperglycemia and was not further evaluated. Isoflurane anesthesia only mildly increased blood glucose levels and had no significant effect on tumor (18)F-FDG uptake. Isoflurane markedly reduced (18)F-FDG uptake by brown adipose tissue and skeletal muscle but increased the activity concentration in liver, myocardium, and kidney. CONCLUSION: Animal handling has a dramatic effect on (18)F-FDG biodistribution and significantly influences the results of microPET studies in tumor-bearing mice. To improve tumor visualization mice should be fasted and warmed before (18)F-FDG injection and during the uptake period. Isoflurane appears well suited for anesthesia of tumor-bearing mice, whereas ketamine/xylazine should be used with caution, as it may induce marked hyperglycemia.

Animal Husbandry↗
PubMed2006

Semiautomated analysis of small-animal PET data.

UNLABELLED: The objective of the work reported here was to develop and test automated methods to calculate biodistribution of PET tracers using small-animal PET images. METHODS: After developing software that uses visually distinguishable organs and other landmarks on a scan to semiautomatically coregister a digital mouse phantom with a small-animal PET scan, we elastically transformed the phantom to conform to those landmarks in 9 simulated scans and in 18 actual PET scans acquired of 9 mice. Tracer concentrations were automatically calculated in 22 regions of interest (ROIs) reflecting the whole body and 21 individual organs. To assess the accuracy of this approach, we compared the software-measured activities in the ROIs of simulated PET scans with the known activities, and we compared the software-measured activities in the ROIs of real PET scans both with manually established ROI activities in original scan data and with actual radioactivity content in immediately harvested tissues of imaged animals. RESULTS: PET/atlas coregistrations were successfully generated with minimal end-user input, allowing rapid quantification of 22 separate tissue ROIs. The simulated scan analysis found the method to be robust with respect to the overall size and shape of individual animal scans, with average activity values for all organs tested falling within the range of 98% +/- 3% of the organ activity measured in the unstretched phantom scan. Standardized uptake values (SUVs) measured from actual PET scans using this semiautomated method correlated reasonably well with radioactivity content measured in harvested organs (median r = 0.94) and compared favorably with conventional SUV correlations with harvested organ data (median r = 0.825). CONCLUSION: A semiautomated analytic approach involving coregistration of scan-derived images with atlas-type images can be used in small-animal whole-body radiotracer studies to estimate radioactivity concentrations in organs. This approach is rapid and less labor intensive than are traditional methods, without diminishing overall accuracy. Such techniques have the possibility of saving time, effort, and the number of animals needed for such assessments.

Algorithms↗
PubMed2006

Predicting chemotherapy response to paclitaxel with 18F-Fluoropaclitaxel and PET.

UNLABELLED: Paclitaxel is used as a chemotherapy drug for the treatment of various malignancies, including breast, ovarian, and lung cancers. To evaluate the potential of a noninvasive prognostic tool for specifically predicting the resistance of tumors to paclitaxel therapy, we examined the tumoral uptake of (18)F-fluoropaclitaxel ((18)F-FPAC) in mice bearing human breast cancer xenografts by using small-animal-dedicated PET and compared (18)F-FPAC uptake with the tumor response to paclitaxel treatment. METHODS: PET data were acquired after tail vein injection of approximately 9 MBq of (18)F-FPAC in anesthetized nude mice bearing breast cancer xenografts. Tracer uptake in reconstructed images was quantified by region-of-interest analyses and compared with the tumor response, as measured by changes in tumor volume, after treatment with paclitaxel. RESULTS: Mice with tumors that progressed demonstrated lower tumoral uptake of (18)F-FPAC than mice with tumors that did not progress or that regressed (r = 0.55, P < 0.02; n = 19), indicating that low (18)F-FPAC uptake was a significant predictor of chemoresistance. Conversely, high (18)F-FPAC uptake predicted tumor regression. This relationship was found for mice bearing xenografts from cell lines selected to be either sensitive or intrinsically resistant to paclitaxel in vitro. CONCLUSION: PET data acquired with (18)F-FPAC suggest that this tracer holds promise for the noninvasive quantification of its distribution in vivo in a straightforward manner. In combination with approaches for examining other aspects of resistance, such quantification could prove useful in helping to predict subsequent resistance to paclitaxel chemotherapy of breast cancer.

Animals↗
PubMed2005

Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer.

Inhibitors of the kinase mammalian target of rapamycin (mTOR) have shown sporadic activity in cancer trials, leading to confusion about the appropriate clinical setting for their use. Here we show that loss of the Von Hippel-Lindau tumor suppressor gene (VHL) sensitizes kidney cancer cells to the mTOR inhibitor CCI-779 in vitro and in mouse models. Growth arrest caused by CCI-779 correlates with a block in translation of mRNA encoding hypoxia-inducible factor (HIF1A), and is rescued by expression of a VHL-resistant HIF1A cDNA lacking the 5' untranslated region. VHL-deficient tumors show increased uptake of the positron emission tomography (PET) tracer fluorodeoxyglucose (FDG) in an mTOR-dependent manner. Our findings provide preclinical rationale for prospective, biomarker-driven clinical studies of mTOR inhibitors in kidney cancer and suggest that FDG-PET scans may have use as a pharmacodynamic marker in this setting.

5' Untranslated Regions↗
PubMed2005

Myocardial perfusion reserve in adults with cyanotic congenital heart disease.

In patients with cyanotic congenital heart disease (CCHD), a right-to-left shunt results in systemic hypoxemia. Systemic hypoxemia incites a compensatory erythrocytosis, which increases whole blood viscosity. We considered that these changes might adversely influence myocardial perfusion in CCHD patients. Basal and hyperemic (intravenous dipyridamole) perfusion measurements were obtained with [13N]ammonia positron emission tomographic imaging in left (LV) and right (RV) ventricular and septal myocardium in 14 adults with CCHD [age: 34.1 yr (SD 6.5)]; hematocrit: 62.2% (SD 4.8)] and 10 healthy controls [age: 34.1 yr (SD 6.5)]. In patients, basal perfusion measurements were higher in LV [0.77 (SD 0.24) vs. 0.55 ml x min(-1) x g(-1) (SD 0.09), P < 0.02], septum [0.71 (SD 0.16) vs. 0.49 ml x min(-1) x g(-1) (SD 0.09), P < 0.001], and RV [0.77 (SD 0.30) vs. 0.38 ml x min(-1) x g(-1) (SD 0.09), P < 0.001]. However, basal measurements normalized for the rate-pressure product were similar to those of controls. Calculated oxygen delivery relative to rate-pressure product was higher in the patients [2.2 (SD 0.8) vs. 1.6 (SD 0.4) x 10(-5) ml O2 x min(-1) x g tissue(-1) x (beats x mmHg)(-1) in the LV, P < 0.05, and 2.0 (SD 0.7) vs. 1.4 (SD 0.3) x 10(-5) ml O2 x min(-1) x g tissue(-1) x (beats x mmHg)(-1) in the septum, P < 0.01]. Hyperemic perfusion measurements in CCHD patients did not differ from controls [LV, 1.67 (SD 0.60) vs. 1.95 ml x min(-1) x g(-1) (SD 0.46); septum, 1.44 (SD 0.56) vs. 1.98 ml x min(-1) x g(-1) (SD 0.69); RV, 1.56 (SD 0.56) vs. 1.65 ml x min(-1) x g(-1) (SD 0.64), P = not significant], and coronary vascular resistances were comparable [LV, 55 (SD 25) vs. 48 mmHg x ml(-1) x g x min (SD 16); septum, 67 (SD 35) vs. 50 mmHg x ml(-1) x g x min (SD 21); RV, 59 (SD 26) vs. 61 mmHg x ml(-1) x g x min (SD 27), P = not significant]. These findings suggest that adult CCHD patients have remodeling of the coronary circulation to compensate for the rheologic changes attending chronic hypoxemia.

Adult↗
PubMed2005

Presurgical staging of non-small cell lung cancer: positron emission tomography, integrated positron emission tomography/CT, and software image fusion.

PURPOSES: To compare the diagnostic accuracy of positron emission tomography (PET) and integrated PET/CT and to evaluate the performance of software fusion for staging of non-small cell lung cancer (NSCLC). METHODS: Thirty-six patients (17 men and 19 women) with NSCLC underwent staging with integrated PET/CT followed by mediastinal lymph node dissection and tumor resection. Twenty-five of the 36 patients (69%) underwent separate CT studies for software fusion of images. Two blinded reviewers analyzed in consensus all PET images, and an experienced radiologist was added to assess integrated and software-fused PET/CT images. Histopathologic findings served as "gold standard" for determining the diagnostic accuracy of all modalities. RESULTS: Reviewers examining PET and integrated PET/CT classified T stage accurately in 67% (20 of 30 patients) and 97% (29 of 30 patients), respectively (p < 0.05). Overall, interpretations based on PET staged 57% (17 of 30 patients) correctly, over-staged 6 patients (20%), and under-staged 7 patients (23%). Interpretations based on integrated PET/CT correctly staged 83% (25 of 30 patients), over-staged 3 patients (10%), and under-staged 2 patients (7%). The overall staging accuracy of integrated PET/CT was significantly higher than that of PET (p < 0.05). Automatic software fusion of separately obtained PET and CT studies was successful in 68% of the patients but failed in 32%. In successful software fusion cases, the results of software fusion with regards to T stage and N stage were not different from integrated PET/CT. CONCLUSIONS: Integrated PET/CT compared with PET alone was associated with 26% points-greater overall diagnostic accuracy (p = 0.01). The software fusion method failed to provide acceptable co-registration in > 30% of the patients.

Aged↗
PubMed2005

Monitoring antiproliferative responses to kinase inhibitor therapy in mice with 3'-deoxy-3'-18F-fluorothymidine PET.

UNLABELLED: The aim of this study was to evaluate, whether PET with (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) may be used to monitor noninvasively the antiproliferative effects of tyrosine kinase inhibitors. METHODS: Using a high-resolution small animal scanner, we measured the effect of the ErbB-selective kinase inhibitor PKI-166 on the (18)F-FDG and (18)F-FLT uptake of ErbB1-overexpressing A431 xenograft tumors. RESULTS: Treatment with PKI-166 markedly lowered tumor (18)F-FLT uptake within 48 h of drug exposure; within 1 wk (18)F-FLT uptake decreased by 79%. (18)F-FLT uptake by the xenografts significantly correlated with the tumor proliferation index as determined by proliferating cell nuclear antigen staining (r = 0.71). Changes in (18)F-FLT uptake did not reflect inhibition of ErbB kinase activity itself but, rather, the effects of kinase inhibition on tumor cell proliferation. Tumor (18)F-FDG uptake generally paralleled the changes seen for (18)F-FLT. However, the baseline signal was significantly lower than that for (18)F-FLT. CONCLUSION: These results indicate that (18)F-FLT PET provides noninvasive, quantitative, and repeatable measurements of tumor cell proliferation during treatment with ErbB kinase inhibitors and provide a rationale for the use this technology in clinical trials of kinase inhibitors.

Animals↗
PubMed2005

Comparison between 18F-FDG PET, in-line PET/CT, and software fusion for restaging of recurrent colorectal cancer.

UNLABELLED: The aim of this study was to compare PET with (18)F-FDG PET, in-line PET/CT, and software fusion of independently acquired CT and PET scans for staging of recurrent colorectal cancer (CRC). METHODS: Fifty-one patients with suspected recurrent CRC were studied with in-line PET/CT. Thirty-four of these patients underwent an additional CT scan of the chest or abdomen within 4 wk of PET/CT. Software fusion of PET and CT was performed using a fully automated, intensity-based algorithm. The accuracy of the coregistration of PET and CT scans was evaluated by measuring the distance between landmarks visible in the PET and CT images. Histologic evaluation and follow-up for 6 mo served as the gold standard for the presence or absence of recurrent CRC. RESULTS: On a patient basis, the accuracy of staging was significantly higher for in-line PET/CT than for PET (88% vs. 71%, P = 0.01). Software fusion of the independently acquired PET and CT images was unsuccessful in 8 patients (24%). In the remaining patients, the mean distance between 62 landmarks visible in PET and CT was 12.9 +/- 7.9 mm, whereas it was only 7.7 +/- 4.7 mm for in-line PET/CT (P < 0.001). CONCLUSION: In patients with suspected recurrent CRC, in-line PET/CT significantly improves staging compared with PET alone. Due to its high failure rate, software fusion of independently acquired PET and CT studies cannot be considered to represent an alternative to in-line PET/CT.

Algorithms↗
PubMed2005

Optimizing imaging protocols for overweight and obese patients: a lutetium orthosilicate PET/CT study.

UNLABELLED: High photon attenuation and scatter in obese patients affect image quality. The purpose of the current study was to optimize lutetium orthosilicate (LSO) PET image acquisition protocols in patients weighing > or =91 kg (200 lb). METHODS: Twenty-five consecutive patients (16 male and 9 female) weighing > or =91 kg (200 lb; range, 91-168 kg [200-370 lb]) were studied with LSO PET/CT. After intravenous injection of 7.77 MBq (0.21 mCi) of 18F-FDG per kilogram of body weight, PET emission scans were acquired for 7 min/bed position. Single-minute frames were extracted from the 7 min/bed position scans to reconstruct 1-7 min/bed position scans for each patient. Three reviewers independently analyzed all 7 reconstructed whole-body images of each patient. A consensus reading followed in cases of disagreement. Thus, 175 whole-body scans (7 per patient) were analyzed for number of hypermetabolic lesions. A region-of-interest approach was used to obtain a quantitative estimate of image quality. RESULTS: Fifty-nine hypermetabolic lesions identified on 7 min/bed position scans served as the reference standard. Interobserver concordance increased from 64% for 1 min/bed position scans to 70% for 3 min/bed position scans and 78% for 4 min/bed position scans. Concordance rates did not change for longer imaging durations. Region-of-interest analysis revealed that image noise decreased from 21% for 1 min/bed position scans to 14%, 13%, and 11% for, respectively, 4, 5, and 7 min/bed position scans. When compared with the reference standard, 14 lesions (24%) were missed on 1 min/bed position scans but only 2 (3%) on 4 min/bed position scans. Five minute/bed position scans were sufficient to detect all lesions identified on the 7 min/bed position scans. CONCLUSION: Lesion detectability and reader concordance peaked for 5 min/bed position scans, with no further diagnostic gain achieved by lengthening the duration of PET emission scanning. Thus, 5 min/bed position scans are sufficient for optimal lesion detection with LSO PET/CT in obese patients.

Female↗
PubMed2005

Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG.

UNLABELLED: 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a recently developed PET tracer to image tumor cell proliferation. We characterized (18)F-FLT PET of brain gliomas and compared (18)F-FLT with (18)F-FDG PET in side-by-side studies of the same patients. METHODS: Twenty-five patients with newly diagnosed or previously treated glioma underwent PET with (18)F-FLT and (18)F-FDG on consecutive days. Three stable patients in long-term remission were included as negative control subjects. Tracer kinetics in normal brain and tumor were measured. Uptake of (18)F-FLT and (18)F-FDG was quantified by the standardized uptake value (SUV) and the tumor-to-normal tissue (T/N) ratio. The accuracy of (18)F-FLT and (18)F-FDG PET in evaluating newly diagnosed and recurrent gliomas was compared. More than half of the patients underwent resection after the PET study and correlations between PET uptake and the Ki-67 proliferation index were examined. Patients were monitored for a mean of 15.4 mo (range, 12-20 mo). The predictive power of PET for tumor progression and survival was analyzed using Kaplan-Meier statistics. RESULTS: (18)F-FLT uptake in tumors was rapid, peaking at 5-10 min after injection and remaining stable up to 75 min. Hence, a 30-min scan beginning at 5 min after injection was sufficient for imaging. (18)F-FLT visualized all high-grade (grade III or IV) tumors. Grade II tumor did not show appreciable (18)F-FLT uptake and neither did the stable lesions. The absolute uptake of (18)F-FLT was low (maximum-pixel SUV [SUV(max)], 1.33) but image contrast was better than with (18)F-FDG (T/N ratio, 3.85 vs. 1.49). (18)F-FDG PET studies were negative in 5 patients with recurrent high-grade glioma who subsequently suffered tumor progression within 1-3 mo. (18)F-FLT SUV(max) correlated more strongly with Ki-67 index (r = 0.84; P < 0.0001) than (18)F-FDG SUV(max) (r = 0.51; P = 0.07). (18)F-FLT uptake also had more significant predictive power with respect to tumor progression and survival (P = 0.0005 and P = 0.001, respectively). CONCLUSION: Thirty-minute (18)F-FLT PET 5 min after injection was more sensitive than (18)F-FDG to image recurrent high-grade tumors, correlated better with Ki-67 values, and was a more powerful predictor of tumor progression and survival. Thus, (18)F-FLT appears to be a promising tracer as a surrogate marker of proliferation in high-grade gliomas.

Adult↗