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Background: The purpose of this study was to test whether nutritional status of patients with head and neck cancer changes during and after treatment., Methods: Nutritional status (including body weight, lean mass, and fat mass) and dietary intake were assessed in 29 patients with head and neck cancer. Patients were assessed 1 week before, and 1 and 4 months after treatment (radiotherapy, either alone or combined with chemotherapy or surgery)., Results: During treatment, body weight (-3.6 ± 5.3 kg; p = .019) and lean mass (-2.43 ± 2.81 kg; p = .001) significantly declined. Patients with sufficient intake (≥35 kcal and ≥1.5 grams protein/kg body weight) lost less body weight and lean mass than patients with insufficient intake (mean difference, -4.0 ± 1.9 kg; p = 0.048 and -2.1 ± 1.0 kg; p = .054, respectively). After treatment, only patients with sufficient intake gained body weight (2.3 ± 2.3 kg) and lean mass (1.2 ± 1.3 kg)., Conclusion: Patients with head and neck cancer fail to maintain or improve nutritional status during treatment, despite sufficient intake., (Copyright © 2010 Wiley Periodicals, Inc.)

Purpose: (18)F-Fluorodeoxyglucose positron emission tomography (FDG PET) has been used to assess metabolic response several months after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer. However, whether a metabolic response can be observed already during treatment and thus can be used to predict treatment outcome is undetermined., Methods: Ten medically inoperable patients with FDG PET-positive lung tumours were included. SBRT consisted of three fractions of 20 Gy delivered at the 80% isodose at days 1, 6 and 11. FDG PET was performed before, on day 6 immediately prior to administration of the second fraction of SBRT and 12 weeks after completion of SBRT. Tumour metabolism was assessed semi-quantitatively using the maximum standardized uptake value (SUV(max)) and SUV(70%)., Results: After the first fraction, median SUV(max) increased from 6.7 to 8.1 (p = 0.07) and median SUV(70%) increased from 5.7 to 7.1 (p = 0.05). At 12 weeks, both median SUV(max) and median SUV(70%) decreased by 63% to 3.1 (p = 0.008) and to 2.5 (p = 0.008), respectively., Conclusion: SUV increased during treatment, possibly due to radiation-induced inflammation. Therefore, it is unlikely that (18)F-FDG PET during SBRT will predict treatment success.

Introduction: Positron emission tomography (PET) using amino acid tracers is able to establish biochemical tumour characterization in vivo. The use of PET in the follow-up of non-functioning pituitary adenomas (NFA) and growth hormone producing pituitary adenomas (GHA) after surgery and radiation treatment is not yet clear., Methods: To determine the value of PET before and after transsphenoidal neurosurgery in NFA and GHA, we investigated 12 patients with pituitary adenoma (9 NFA and 3 GHA) before and 4 months after surgery with magnetic resonance imaging (MRI) and tyrosine PET (TYR-PET). Three years after radiation therapy TYR-PET was used to document residual activity in 6 of these patients (4 NFA- and 2 GHA). Tumour size was quantified by computerized MRI measurements. In TYR-PET, tumour activity was assessed by computerized measurements of the hot spot and by determination of protein synthesis rate (PSR)., Results: In response to surgery, MRI showed a median tumour volume reduction of 58% (P<0.01). TYR-PET demonstrated 62% volume reduction (P<0.02), but no change in PSR (P>0.30). After radiation therapy the MRI-volumes of the residual pituitary adenomas did not change but the volume of the hot spot on TYR-PET-imaging was reduced by 58% (P=0.02), and PSR decreased in 5 of 6 patients (P=0.12)., Conclusion: Amino acid PET tumour activity is reduced parallel with MRI volume changes after surgery. The decrease in TYR-PET activity after radiation therapy, despite unaltered MRI tumour volume, supports the concept that it is possible to follow biological tumour activity with this technique. The diagnostic merit of this tracer technique, predicting pituitary adenoma re-growth, needs to be validated in a large prospective study., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: [F-18]-Fluorodeoxyglucose-positron emission tomography (FDG-PET) is used increasingly in the work-up to surgery for patients with potentially resectable colorectal liver metastases. This study evaluates the clinical effectiveness, impact on health care resources and cost-effectiveness of adding FDG-PET to the diagnostic algorithm alongside a randomized clinical trial from a health care perspective., Methods: In a randomized clinical trial, the net monetary benefit (NMB) of FDG-PET added to conventional diagnostic work-up (CWU) was determined in patients with colorectal liver metastases. Seventy-five patients were included in each arm. Change in clinical management, futile laparotomies, preoperative findings and all relevant health care consumption were prospectively documented during 3 years. To assess health-related quality of life European Quality of Life-5 Dimensions was administered at the time of randomization, 3 and 6 weeks postoperatively, and every 3 months postoperatively for 3 years. Quality-adjusted life years (QALYs) were calculated based on European Quality of Life-5 Dimensions outcomes., Results: In adding FDG-PET, diagnostic performance increased and futile laparotomies were reduced by 38%. Both health-related quality of life and QALYs showed no significant difference between the CWU and PET groups. For CWU and PET groups costs were euro 92,836 and euro 81,776, respectively, accumulated in 3 years after randomization. NMB ranged from euro 1004 to euro 11,060 depending on the monetary value given to a QALY. When costs for chemotherapy were disregarded, costs amounted to euro 15,874 for CWU and euro 18,664 for PET group., Conclusion: Additional costs of FDG-PET in the diagnostic work-up of patients with potentially resectable colorectal liver metastases were compensated by a reduction in futile laparotomies. The NMB analysis showed savings over a relevant range of willingness to pay for a QALY.

Background: A disadvantage of 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET) in head and neck cancer is that (18)F-FDG uptake is not specific to malignant tissue. To provide an alternative, radiolabeled amino acids such as L-1-[(11)C]-tyrosine ((11)C-TYR), were introduced because these are less avidly metabolized by inflammatory cells., Methods: In this prospective study, we compared both (11)C-TYR PET and (18)F-FDG PET performance in detecting cervical metastases in 27 patients with a squamous cell carcinoma (SCC) of oral cavity or oropharynx., Results: (11)C-TYR PET sensitivity, specificity, and accuracy for detecting nodal metastases were 33%, 100%, and 81%, respectively. With respect to (18)F-FDG PET, these figures were 67%, 97%, and 89%, respectively. Neck metastases not detected by (11)C-TYR PET were camouflaged by high tracer uptake by salivary glands., Conclusions: Because of bilateral accumulation of (11)C-TYR in salivary glands, (11)C-TYR PET is not suitable to replace (18)F-FDG PET in staging SCC of oral cavity and oropharynx.

Purpose: Good observer agreement is mandatory for an effective imaging technique. However, little is known about the observer agreement of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) in head and neck squamous cell carcinoma. The aim of the present study was to evaluate the inter- and intraobserver agreement of interpretations of (18)F-FDG PET in head and neck SCC and to assess the influence of observer experience, tumor localizing, and tumor size on the agreement., Patients and Methods: (18)F-FDG PET scans of 80 patients with oral and oropharyngeal SCC were reassessed twice by 2 experienced nuclear medicine physicians and 2 residents in nuclear medicine. The absolute agreement and Cohen's kappa were calculated by comparing the results of the 4 observers for the primary tumor, cervical metastases, and distant metastases/second primary tumor. To analyze the sensitivity and specificity, the results were compared with the findings from the histologic specimens or the follow-up data., Results: The interobserver agreement of the nuclear medicine physicians revealed an absolute agreement and kappa of 0.91 and 0.58 for detecting the primary tumor, 0.94 and 0.83 for detecting cervical metastases, and 0.85 and 0.53 for detecting distant metastases/second primary tumors, respectively. The intraobserver agreement was greater overall than the interobserver agreement. Compared with the nuclear medicine physicians, the residents scored lower in interobserver agreement. The interobserver agreement decreased when localizing the malignancy more precisely. The agreement and sensitivity increased with tumor size. However, for small metastases, a high observer agreement was found owing to the nondetection of these malignancies., Conclusions: Good inter- and intraobserver agreement in SCC in the oral cavity or oropharynx with (18)F-FDG PET was found. Observer experience had limited influence on observer agreement. However, the agreement level decreased when a more precise anatomic tumor localization was required.

Detection of distant metastases and second primary tumors in patients with head and neck squamous cell carcinoma (HNSCC) is of importance because of the impact on treatment and prognosis. The aim of this study was to assess the value of whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET) in detecting distant metastases and second primary tumors below clavicular level in HNSCC compared to chest CT and chest radiography (CXR). Patient records of 149 consecutive patients with a primary HNSCC in whom a whole-body FDG-PET for initial staging was performed were reviewed. FDG-PET showed a sensitivity and specificity for detecting distant disease of 92% and 93%, respectively. Chest CT (n=82) showed a sensitivity and a specificity of 74% and 61% respectively. CXR (n=106) showed a sensitivity and a specificity of 41% and 91%, respectively. FDG-PET was shown to be able to detect distant metastases and second primary tumors in HNSCC with a high sensitivity and specificity. The higher sensitivity of PET compared to chest CT is mainly due to the detection of extrapulmonary malignancy. Sensitivity of PET and CT were similar in detecting intrapulmonary malignancy, but PET specificity was significantly higher. FDG-PET helps to determine the nature of pulmonary lesions and might be considered as a first diagnostic modality for detecting distant disease in advanced HNSCC.

Background: Whereas haemodialysis (HD) is lifesaving by replacement of renal function, there are data to suggest that the HD procedure itself may contribute to the high cardiac risk in dialysis patients. The HD procedure is associated with an increased risk of sudden death, and there is accumulating evidence that HD can elicit myocardial ischaemia. In this study, we evaluated the effect of HD on global and regional myocardial blood flow (MBF) and left ventricular (LV) function in non-diabetic, non-cardiac compromised patients., Methods: (13)N-NH(3) positron emission tomography (PET) was used to quantify changes in MBF, LV wall motion, cardiac output (CO), LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) in seven non-diabetic patients with uneventful cardiac histories. PET scans were performed before and at 30 and 220 min of HD., Results: In all patients global MBF fell during HD. At 30 min of HD without ultrafiltration (UF), global MBF had fallen 13.5 +/- 11.5% (P < 0.05) while CO, LVEDV and LVESV were 4.6 +/- 5.3% (NS), 5.6 +/- 4.2% (P < 0.05) and 6.9 +/- 7.2% (P < 0.05) lower, respectively. At 220 min of HD, after UF of 2.5 +/- 0.9 l, global MBF had fallen 26.6 +/- 13.9% (P < 0.05) from baseline while CO, LVEDV and LVESV were 21.0 +/- 19.7%, 31.1 +/- 12.7% and 36.4 +/- 17.5% (all P < 0.05) lower, respectively. In two patients, new LV regional wall motion abnormalities (RWMA) developed at 220 min of HD. MBF was reduced to a greater extent in regions that developed LV RWMA compared to those that did not., Conclusions: Haemodialysis induced a pronounced fall in MBF. Since MBF fell already early during HD not only hypovolaemia but also acute dialysis-associated factors seem to play a role. Haemodialysis-associated reductions in MBF may contribute to the high cardiac event rate of dialysis patients.

Introduction: Standard uptake value (SUV) is a quantitative measure for the preferential uptake of a radiopharmaceutical in a tumor compared with the homogeneous distribution in the body. SUV can be based on the maximal value of one pixel (SUVmax) or on the mean value in a region outlined by isodensity contours. The prognostic value of different SUVs in non-small cell lung cancer (NSCLC) is not established. We evaluated this value for SUVmax, SUV70%, and SUV50% among patients with resectable NSCLC., Methods: All consecutive patients with resectable NSCLC who underwent an attenuation-corrected whole-body fluorine-18 fluorodeoxyglucose positron emission tomography scan from two university hospitals were selected. By adjusting the isocontour in the region of interest on the scan, SUVmax, SUV70%, and SUV50% of the primary tumor were calculated., Results: Sixty-six patients (50 male, median age 63 years) were included. Of the tumors, 16 were pathological stage IA, 23 were IB, 4 were IIA, 14 were IIB, and 9 were IIIA. Median (range) values for SUVmax, SUV70%, and SUV50% were 6.4 (1.6-19.1), 5.1 (1.0-15.7), and 4.0 (0.9-13.4), respectively. SUVs were associated with survival. Analysis of residuals of SUVmax as a continuous variable in a Cox's proportional hazard model for survival suggested no cutoff point and no indication of time-dependency. Patients with a SUV higher than the median value had a worse survival than patients with a SUV lower than median (hazard ratios for SUVmax, SUV70%, and SUV50% all were 2.9; p = 0.02)., Conclusions: SUVmax, SUV70%, and SUV50% measured with fluorine-18 fluorodeoxyglucose positron emission tomography have a similar prognostic value, and no "natural" cutoff point for SUVmax in resectable NSCLC was identified.

Unlabelled: The aim of this prospective study was to evaluate the value of (18)F-FDG PET for the assessment of chemotherapy response in patients with non-small cell lung cancer. Furthermore, part of the objective of this study was to compare 2 methods to quantify changes in glucose metabolism., Methods: In 51 patients, dynamic (18)F-FDG PET was performed before and at 5-8 wk into treatment. Simplified methods to measure glucose metabolism (standardized uptake value [SUV]) and quantitative measures (metabolic rate of glucose [MR(Glu)]), derived from Patlak analysis, were evaluated. The overall survival and progression-free survival with respect to MR(Glu) and SUV were calculated using Kaplan-Meier estimates. Fractional changes in tumor glucose use were stratified by the median value and also the predefined EORTC (European Organization for Research and Treatment of Cancer) metabolic response criteria, and criteria applying cutoff levels similar to those of RECIST (Response Evaluation Criteria in Solid Tumors) were evaluated., Results: When stratifying at the median value of DeltaMR(Glu) and DeltaSUV, the difference in overall survival (P = 0.017 for DeltaMR(Glu), P = 0.018 for DeltaSUV) and progression-free survival (P = 0.002 for DeltaMR(Glu), P = 0.0009 for DeltaSUV) was highly significant. When applying the predefined criteria for metabolic response, the cutoff levels as also used for size measurement (RECIST) showed significant differences for DeltaSUV between response categories in progression-free survival (P = 0.0003) as well as overall survival (P = 0.027)., Conclusion: The degree of chemotherapy-induced changes in tumor glucose metabolism as determined by (18)F-FDG PET is highly predictive for patient outcome, stratifying patients into groups with widely differing overall survival and progression-free survival probabilities. The use of (18)F-FDG PET for therapy monitoring seems clinically feasible, because simplified methods to measure tumor glucose use (SUV) are sufficiently reliable and can replace more complex, quantitative measures (MR(Glu)) in this patient population.

Purpose: Standardised uptake values (SUVs) depend on acquisition, reconstruction and region of interest (ROI) parameters. SUV quantification in multi-centre trials therefore requires standardisation of acquisition and analysis protocols. However, standardisation is difficult owing to the use of different scanners, image reconstruction and data analysis software. In this study we evaluated whether SUVs, obtained at three different institutes, may be directly compared after calibration and correction for inter-institute differences., Methods: First, an anthropomorphic thorax phantom containing variously sized spheres and activities, simulating tumours, was scanned and processed in each institute to evaluate differences in scanner calibration. Secondly, effects of image reconstruction and ROI method on recovery coefficients were studied. Next, SUVs were derived for tumours in 23 subjects. Of these 23 patients, four and ten were scanned in two institutes on an HR+ PET scanner and nine were scanned in one institute on an ECAT EXACT PET scanner. All phantom and clinical data were reconstructed using iterative reconstruction with various iterations, with both measured (MAC) and segmented attenuation correction (SAC) and at various image resolutions. Activity concentrations (AC) or SUVs were derived using various ROI isocontours., Results: Phantom data revealed differences in SUV quantification of up to 30%. After application-specific calibration, recovery coefficients obtained in each institute were equal to within 15%. Varying the ROI isocontour value resulted in a predictable change in SUV (or AC) for both phantom and clinical data. Variation of image resolution resulted in a predictable change in SUV quantification for large spheres/tumours (>5 cc) only. For smaller tumours (<2 cc), differences of up to 40% were found between high (7 mm) and low (10 mm) resolution images. Similar differences occurred when data were reconstructed with a small number of iterations. Finally, no significant differences between MAC and SAC reconstructed data were observed, except for tumours near the diaphragm., Conclusion: Standardisation of acquisition, reconstruction and ROI methods is preferred for SUV quantification in multi-centre trials. Small unavoidable differences in methodology can be accommodated by performing a phantom study to assess inter-institute correction factors.

This study was set up to demonstrate whether prognostic classification based on the secondary age-adjusted International Prognostic Index (sAA-IPI) for recurring aggressive non-Hodgkin lymphoma (NHL) or the prognostic score for recurring Hodgkin lymphoma (HL) can be improved by including the midtreatment results of fluorine-18-fluorodeoxy-glucose-positron emission tomography (FDG-PET). Clinical data on patients with recurring lymphoma who were treated with second-line chemotherapy (DHAP-VIM-DHAP) followed by autologous stem cell transplantation (ASCT) were collected and combined with the results of FDG-PET performed before and after 2 cycles of reinduction chemotherapy. PET responses after 2 courses were scored as complete remission (CR), partial remission (PR), or no response (NR). A multivariate analysis was performed to design a predictive model. The number of patients (101 of 117) included those (78 patients with aggressive NHL and 23 patients with HL) that could be analyzed according to protocol. Of these, 80 patients were chemosensitive and 77 received transplants. Both secondary clinical risk score (P<.001) and FDG-PET response (P<.001) were independent predictive factors for the total evaluable group of patients with lymphoma and for patients with NHL alone. The combined use of the clinical risk score and FDG-PET response after 2 chemotherapy courses identified at least 4 categories of patients with a failure-free survival varying between 5% to 100% after transplantation (P<.001). These data indicate that the secondary clinical risk score in conjunction with FDG-PET response provides a more accurate prognostic instrument for the outcome of second-line treatment at least in patients with recurring NHL.

Fever of unknown origin (FUO) frequently complicates the management of pediatric patients with terminal chronic liver failure during the pretransplantation period and may lead to increased morbidity and mortality. Nonhepatic origins of systemic infections may render the patient unsuitable for transplantation whereas infections within the liver may require organ resection for a cure. Therefore, accurate localization of the infection focus is critical for optimal management of children on the waiting list for liver transplantation. Here we report our experience using [18 F]fluordeoxyglucose (FDG)-positron emission tomography (PET) to detect the origin of infection in 11 children with biliary cirrhosis presenting with FUO during the waiting period for liver transplantation. In 5 children, positive intrahepatic FDG-PET signals correlated with bacterial cultures of the excised liver and/or anatomic or histologic signs of infection. Based on the FDG-PET findings, these patients underwent transplantation after continuous antibiotic treatment with ongoing, recurrent episodes of fever. In 6 children, no abnormal hepatic FDG-PET signals were found and no infections could be detected in the liver. Transplantation in these patients was performed only after becoming afebrile. Standard imaging techniques did not reveal abnormalities compatible with infection in any of the children. In conclusion, in children with biliary cirrhosis and FUO on the waiting list for liver transplantation, information obtained by FDG-PET imaging may be useful for decisions on therapy and suitability for liver transplantation., ((c) 2006 AASLD)

Unlabelled: The use of dynamic (18)F-FDG PET to determine changes in tumor metabolism requires tumor and plasma time-activity curves. Because arterial sampling is invasive and laborious, our aim was to validate noninvasive image-derived input functions (IDIFs)., Methods: We obtained 136 dynamic (18)F-FDG PET scans of 76 oncologic patients. IDIFs were determined using volumes of interest over the left ventricle, ascending aorta, and abdominal aorta. The tumor metabolic rate of glucose (MRGlu) was determined with the Patlak analysis, using arterial plasma time-activity curves and IDIFs., Results: MRGlu using all 3 IDIFs showed a high correlation with MRGlu based on arterial sampling. Comparability between the measures was also high, with the intraclass correlation coefficient being 0.98 (95% confidence interval, 0.97-0.99) for the ascending aorta IDIF, 0.94 (0.92-0.96) for the left ventricle IDIF, and 0.96 (0.93-0.98) for the abdominal aorta IDIF., Conclusion: The use of IDIFs is accurate and simple and represents a clinically viable alternative to arterial blood sampling.

Purpose: We investigated whether application of positron emission tomography (PET) immediately after first presentation might simplify staging while maintaining accuracy, as compared with traditional strategy in routine clinical setting., Methods: At first presentation, patients with a provisional diagnosis of lung cancer without overt dissemination were randomly assigned to traditional work-up (TWU) according to international guidelines or early PET followed by histologic/cytologic verification of lesions, or imaging and follow-up. Patients with [18F] fluorodeoxyglucose (18FDG) -avid, noncentral tumors without suspicion of mediastinal or distant metastases on PET proceeded directly to thoracotomy. Follow-up in presumed benign lesions was at least 12 months. In patients treated with surgery or neoadjuvant therapy, the quality of staging was measured by comparing the clinical stage to the final stage (combination of peroperative staging and 6 months of follow-up). To investigate test substitution, we analyzed the number of (non)invasive tests to achieve clinical TNM staging, and its associated costs., Results: Between 1999 and 2001, 465 patients (233 TWU, 232 PET) were enrolled at 22 hospitals. The mean (standard deviation) number of procedures to finalize staging was equal in the TWU arm and the PET arm: 7.9 (2.0) v 7.9 (1.9), P = .90, respectively. Mediastinoscopies occurred significantly less often in the PET arm. Agreement between clinical and final stage was good in both arms (kappa = .85 v .78; P = .07). Costs did not differ significantly., Conclusion: Up-front 18FDG-PET in patients with (suspected) lung cancer does not reduce the overall number of diagnostic test, but it maintains quality of TNM staging with the use of less invasive surgery.

Background and Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) appears to be an excellent tool for evaluating early response to chemotherapy in lymphoma patients. As only chemosensitive patients with relapsed lymphoma may benefit from ablative therapy and autologous stem cell transplantation (ASCT), PET may be used to select patients for ASCT. A prospective study was performed to investigate the optimal time point of pre-transplantation PET, using different PET-parameters., Design and Methods: Three serial whole-body attenuation-corrected FDG-PET scans were performed in 39 consecutive patients with relapsed lymphoma (28 with aggressive non-Hodgkin's lymphoma and 11 with Hodgkin's disease) eligible for second-line chemotherapy followed by ASCT: PET1 before treatment, PET2 after two cycles of induction chemotherapy and PET3 after a third cycle of chemotherapy just before ASCT in cases with an abnormal PET2. Visual analysis and standardized uptake value (SUV) parameters were obtained for each scan. The follow-up lasted a minimum of 6 months after ASCT., Results: PET2 normalized in 43% (17/39) of the patients, and PET3 normalized in 27% (6/22). Persistent abnormal FDG-uptake was observed in 41% of the patients: 15% showed partial remission and 26% stable or even progressive abnormalities. With a median follow-up of 22 months (range 6-55) 54% of all patients relapsed after ASCT. The results demonstrated that those patients who showed a complete response after the second and third cycles of chemotherapy had a 2-year progression-free survival of 71% and 58%, respectively, while those who showed no response, all relapsed shortly after ASCT. Analysis of the SUV parameters did not reveal additional information compared to that yielded by the visual assessment., Interpretation and Conclusions: Two serial PET scans predict outcome after ASCT more precisely than one interim PET in patients with relapsed lymphoma.

Purpose: Prostate cancer is the second leading cause of death from cancer among US men. Positron emission tomography (PET) with [(11)C]choline has been shown to be useful in the staging and detection of prostate cancer. The background of the increased uptake of choline in human prostate cancer is not completely understood. The aim of this study was to prospectively investigate the relationship between the [(11)C]choline uptake and the cell proliferation in human prostate cancer., Methods: Prostate cancer tissue from 18 patients who had undergone a radical prostatectomy for histologically proven disease was studied. An [(11)C]choline PET scan was performed prior to surgery. Post-prostatectomy specimens were prepared and stained with the antibody MIB-1 for Ki-67, which depicts proliferation. Two independent observers counted the amount of stained nuclei per specimen., Results: Prostate cancer showed Ki-67 staining and high uptake of [(11)C]choline. Statistical analysis showed no significant correlation between [(11)C]choline uptake and Ki-67 staining (R=0.23; P=0.34). No significant relationships were found between the uptake of [(11)C]choline (SUV) and either preoperative PSA (R=0.14; P=0.55) or Gleason sum score (R=0.28; P=0.25)., Conclusion: In vivo uptake of [(11)C]choline does not correlate with cell proliferation in human prostate cancer as depicted by Ki-67. Our results suggest that a process other than proliferation is responsible for the uptake of [(11)C]choline in prostate cancer.

Unlabelled: Choosing the optimal treatment for an individual with squamous cell carcinoma of the head and neck is a difficult challenge because of the unpredictable clinical behavior of this malignancy. A reliable method for assessing the clinical behavior and predicting the radiocurability of tumors would assist in the therapy strategy and prognosis. This study evaluated whether quantitative PET using l-[1-(11)C]-tyrosine (TYR) has predictive value for survival and therapy outcome in patients with primary squamous cell carcinoma of the larynx., Methods: Thirty-four patients with histologically confirmed laryngeal carcinomas underwent dynamic (11)C-TYR PET before receiving definitive therapy. Various methods for quantification of tumor activity were used: assessment of protein synthesis rate (PSR), calculation of standardized uptake value, and estimation of tumor-to-nontumor ratio. Treatment consisted of radiotherapy (n = 20) or surgery (n = 14). The median follow-up was 40 mo., Results: All malignancies were identified correctly, with no false-negative results. Cumulative survival was compared between patients with tumor PSR equal to or higher than the median (2.0 nmol/mL/min) and those with tumor PSR lower than the median and was found not to be significantly different (P = 0.07). When the radiotherapy group was evaluated separately, the difference in survival was significant (P = 0.03; 5-y survival, 30% vs. 73%) and high (11)C-TYR uptake correlated with poor prognosis. In multivariate analysis, PSR was an independent predictor for survival. Because differences (P = 0.08) between patients with and patients without recurrence were not significant, no predictive value of PSR for disease recurrence could be demonstrated., Conclusion: Prediction of survival of patients undergoing radiotherapy for laryngeal squamous cell carcinoma is feasible primarily by using (11)C-TYR PET to quantify activity before treatment.

Unlabelled: Prostate cancer is known for its difficulties in preoperative staging of pelvic lymph nodes by conventional imaging techniques. Thus, a histopathologic examination of the pelvic lymphadenectomy specimen is mandatory for patients at risk for metastatic disease. The aim of this study was to evaluate the strength and accuracy of (11)C-choline PET in preoperative noninvasive staging of pelvic lymph nodes in prostate cancer., Methods: In a prospective study we examined 67 consecutive patients with histologically proven prostate cancer with (11)C-choline PET. The results of PET were compared with the results of histology of the pelvic lymph nodes and with the follow-up data. Conventional axial imaging was routinely performed using MRI or CT. The sensitivity, specificity, and accuracy of (11)C-choline PET were calculated., Results: Fifteen patients had histologically proven lymph node metastases. (11)C-Choline PET was true-positive in 12 of 15 patients and false-negative in 3 patients. Fifty-two patients had no lymph node metastases. (11)C-Choline PET was true-negative in 50 of 52 patients and false-positive in 2 patients. We calculated a sensitivity of (11)C-choline PET for staging metastatic lymph node disease of 80%, a specificity of 96%, and an accuracy of 93%. Next, (11)C-choline PET detected solitary extraregional lymph node metastases in 5 of 12 patients with nodal metastases., Conclusion: This study showed that (11)C-choline PET is sensitive and accurate in preoperative staging of pelvic lymph nodes in prostate cancer.

Unlabelled: PET with L-1-(11)C-tyrosine (TYR) can measure and quantify increased protein synthesis in tumor tissue in vivo. For quantification of the protein synthesis rate (PSR), arterial cannulation with repeated blood sampling to obtain the plasma input function and a dynamic TYR PET study to calculate a time-activity curve are necessary. In most PET studies the standardized uptake value (SUV) method is used to quantify tumor activity. The SUV can be calculated without repeated arterial blood sampling and prolonged scanning time, as required for determination of the PSR. The relationship between PSR and SUV is largely unknown and different factors can cause wide variability in the SUV. Therefore, the comparison of the absolute quantification method (PSR) with the SUV method is obligatory to determine the possible use of noninvasive PET in head and neck oncology., Methods: Twenty-four patients with proven squamous cell carcinomas of the larynx (T1-T4) were studied using dynamic TYR PET. The PSRs of tumor and nontumor (background) regions were determined. Four different methods were used to calculate the SUV: uncorrected SUV (SUV(BW)); and SUVs corrected for body surface area (SUV(BSA)), for lean body mass (SUV(LBM)), and for the Quetelet index (SUV(QI)). Correlations between PSR values and SUVs were calculated., Results: The PSR of all tumors was significantly higher (P < 0.001) than the PSR of nontumor tissue. The correlations of SUV(BW), SUV(BSA), SUV(LBM), and SUV(QI) with the quantitative values of the PSR were high (r = 0.84-0.90). The best correlation was observed with the SUV based on the LBM (SUV(LBM))., Conclusion: High correlation between the quantitative values (PSR) and the SUVs offers the possibility to use noninvasive TYR PET for detection and reliable quantification of primary head and neck tumors.

The 5-HT(1A) receptor has been implicated in a variety of physiological processes, psychiatric disorders, and neurodegenerative disorders. [(18)F]MPPF is a useful radioligand for quantitative imaging of 5-HT(1A) receptors in human subjects. Previous studies have shown that the binding of some radioligands is sensitive to changes in neurotransmitter concentration, whereas in other cases, binding is not affected. In the present study we investigated if [(18)F]MPPF binding to the 5-HT(1A) receptor is sensitive to changes in 5-HT. Changes in 5-HT levels were achieved by influencing its synthesis through tryptophan depletion, including a tryptophan-free amino acid drink 4.5 h prior to the PET scan and tryptophan infusion (10 mg/ml, 50 mg/kg, 30 min, starting 60 min prior to the PET scan). Binding of [(18)F]MPPF in the brain of six healthy, male volunteers was compared in these two conditions. Mean binding potentials in the medial temporal cortex, cortical regions, and raphe nucleus did not significantly differ between the two conditions. The results of the study show that, under the experimental conditions used, [(18)F]MPPF binding was not affected. It is hypothesized that the increases in 5-HT levels needed to produce a measurable effect on [(18)F]MPPF binding would be significantly greater than that possible with tryptophan manipulation. Therefore, in pathological conditions, where such large increases in 5-HT levels are not expected, [(18)F]MPPF seems a useful ligand to measure 5-HT(1A) receptor distribution without the interference of endogenous 5-HT., (Copyright 2002 Wiley-Liss, Inc.)

Fluorine-18 fluorodeoxyglucose (FDG), the most widely used radiopharmaceutical in positron emission tomography (PET) for oncological purposes, is unsuitable for imaging of bladder cancer owing to high excretion into the urine. More specific PET radiopharmaceuticals which are not excreted into urine would be welcome. Carbon-11 labelled choline (CHOL) is a new radiopharmaceutical potentially useful for tumour imaging and is not excreted into the urine. We prospectively studied the visualisation of bladder cancer using CHOL PET. Eighteen patients with bladder cancer and five healthy volunteers were included. Bladder cancer was first diagnosed by transurethral resection or by biopsy of the tumour. Next, PET images were performed before surgical treatment by cystectomy. The histopathological findings after cystectomy were used as the gold standard. PET images were performed on either an ECAT 951/31 or an ECAT Exact HR+ system. Attenuation-corrected PET images were obtained after injection of 400 MBq CHOL. PET images were analysed by two independent physicians using visual analysis and calculation of the standardised uptake value (SUV). In the normal bladder wall, the uptake of CHOL was low, and the bladder margin was only outlined by minimal urinary radioactivity, if present. In ten patients the tumour was detected correctly by CHOL PET, with an SUV of 4.7+/-3.6 (mean+/-SD). One false positive CHOL PET scan was seen in a patient with an indwelling catheter for 2 weeks prior to the PET scan. In two patients, lymph node metastases were detected by CHOL PET. A micrometastasis <5 mm was not visualised with CHOL PET. In seven patients, no residual tumour was found after surgery. In six of seven patients CHOL PET imaging was negative. In situ carcinoma, dysplasia and a non-invasive urothelial tumour (pTa) remained undetected in three of these six patients. Minimal to no urinary tract radioactivity was seen in 22/23 subjects. Non-specific uptake of CHOL was observed in the small bowel, rectum and prostate gland. CHOL uptake in bladder cancer was avid, visualising the tumour in the virtual absence of urinary radioactivity. No uptake of CHOL was seen in pre-malignant lesions or in small non-invasive tumours. Our results warrant further research into the value of CHOL PET in the clinical management of patients with bladder cancer.

This study evaluated the potential role of L-(1-(11)C)-tyrosine positron emission tomography (TYR PET) for visualisation and quantification of protein metabolism in lung cancer. Dynamic TYR PET scans of the thorax were performed in 17 patients with lung cancer. Protein synthesis rate (PSR in micromol/min x l) and standardised uptake value (SUV, corrected for body measurements) of tumour tissue and contralateral normal tissue were calculated before and after chemotherapy or radiotherapy. All tumours [11 non-small cell lung carcinomas (NSCLCs), five small cell lung carcinomas (SCLCs), and one pleural mesothelioma] were visualised as a hot spot. The median PSR in tumour tissue was higher than that in corresponding contralateral normal lung tissue before [1.88 micromol/min x l (range 1.10-3.42) vs 0.40 micromol/min x l (range 0.12-0.86); P=0.003] and after treatment [1.33 micromol/min x l (range 0.45-2.21) vs 0.28 micromol/min x l (range 0.18-0.51); P<0.02]. In contrast to PSR of normal lung tissue, PSR of tumour tissue decreased significantly after therapy (P=0.03). Before therapy, no significant difference in PSR between NSCLCs and SCLCs was observed, but after therapy the PSR differed significantly between the subgroups [1.69 micromol/min x l (range 0.63-2.78) for NSCLC vs 0.67 micromol/min x l (range 0.45-0.92) for SCLC; P=0.03], irrespective of the treatment modality. The median SUV of tumour tissue was higher than that in corresponding contralateral normal lung both before and after therapy. Only a weak correlation between PSR and SUV was found when the latter was corrected for body surface area or lean body mass. Carbon-11 labelled tyrosine appears to be a good tracer for visualising lung cancer. PSR of tumour tissue can be used to quantify reduction in the metabolic rate of the tumour. Future studies need to be performed to determine whether TYR PET will supply additional clinical information with treatment implications in patients with lung cancer.

Unlabelled: PET with (18)F-FDG is used for detection and staging of thoracic cancer; however, more specific PET radiopharmaceuticals would be welcome. (11)C-labeled choline (CHOL) is a new radiopharmaceutical potentially useful for tumor imaging, since it is incorporated into cell membranes as phosphatidylcholine. The aim of this study was to investigate whether (11)C-CHOL PET has advantages over (18)F-FDG PET in patients with thoracic cancer., Methods: We evaluated 17 patients with thoracic cancer both with (11)C-CHOL PET and (18)F-FDG PET. After transmission scanning, (11)C-CHOL was injected intravenously, and whole-body scanning was started after 5 min. Immediately thereafter, (18)F-FDG was injected intravenously, followed after 90 min by interleaved attenuation-corrected whole-body scanning. Scans were performed from crown to femur. Visual and quantitative (standardized uptake value) analyses of (11)C-CHOL PET and (18)F-FDG PET were performed and compared with results of traditional staging and follow-up., Results: The most prominent features of normal (11)C-CHOL distribution were high uptake in liver, renal cortex, and salivary glands. Except for some uptake in choroid plexus and pituitary gland, brain uptake was negligible. All primary thoracic tumors were detected with (11)C-CHOL PET and (18)F-FDG PET. Both (11)C-CHOL PET and (18)F-FDG PET correctly identified all 16 patients with lymph node involvement. However, in a lesion-to-lesion analysis, (11)C-CHOL PET detected only 29 of 43 metastatic lymph nodes, whereas (18)F-FDG PET detected 41 of 43. (11)C-CHOL PET detected fewer intrapulmonary and pleural metastases than (18)F-FDG PET (27/47 vs. 46/47). More brain metastases were detected with (11)C-CHOL PET (23/23) than with (18)F-FDG PET (3/23). For primary tumors, the median (range) standard uptake values of (11)C-CHOL and (18)F-FDG were 1.68 (0.98-3.22) and 4.22 (1.40-8.26), respectively (P = 0.001)., Conclusion: (11)C-CHOL PET can be used to visualize thoracic cancers. Although detection of lymph node metastases with (11)C-CHOL PET was inferior compared with (18)F-FDG PET, the detection of brain metastases was superior.