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PET with L-1-C-11-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 (SUVBW); and SUVs corrected for body surface area (SUVBSA), for lean body mass (SUVLBM), and for the Quetelet index (SUVQI). Correlations between PSR values and SUVs were calculated. Results: The PSR of all tumors was significantly higher (P

[F-18]-fluorodeoxyglucose ([F-18]-FDG) uptake is enhanced in most malignant tumours which in turn can be measured using positron emission tomography (PET). A number of small clinical trials have indicated that quantification of the change in tumour [F-18]-FDG uptake may provide an early, sensitive, pharmacodynamic marker of the tumoricidal effect of anticancer drugs. This may allow for the introduction of subclinical response for anticancer drug evaluation in early clinical trials and improvements in patient management. For comparison of results from smaller clinical trials and larger-scale multicentre trials a consensus is desirable for: (i) common measurement criteria; and (ii) reporting of alterations in [F-18]-FDG uptake with treatment. This paper summarises the current status of the technique and recommendations on the measurement of [F-18]-FDG uptake for tumour response monitoring from a consensus meeting of the European Organization for Research and Treatment of Cancer (EORTC) PET study group held in Brussels in February 1998 and confirmed at a subsequent meeting in March 1999. (C) 1999 Elsevier Science Ltd. All rights reserved.

PET with L-[1-C-11]-tyrosine (TYR) was investigated in patients undergoing hyperthermic isolated limb perfusion (HILP) with recombinant tumor necrosis factor alpha (rTNF-alpha) and melphalan for locally advanced soft-tissue sarcoma and skin cancer of the lower limb. Methods: Seventeen patients (5 women, 12 men; age range 24-75 y; mean age 52 y) were studied. TYR PET studies were performed before HILP and 2 and 8 wk afterwards. The protein synthesis rates (PSRs) in nanomoles per milliliter per minute were calculated. After final PET studies, tumors were resected and pathologically examined. Patients with pathologically complete responses (pCR) showed no viable tumors after treatment. Those with pathologically partial responses (pPR) showed various amounts of viable tumors in the resected tumor specimens, Results: Six patients (35%) showed a pcR and 11 patients (65%) showed a pPR. All tumors were depicted as hot spots on PET studies before HILP. The PSR in the pCR group at 2 and 8 wk after perfusion had decreased significantly (P 0.91 for having viable tumor after HILP was 100%, whereas the predictive value of a PSR less than or equal to 0.91 for having nonviable tumor tissue after HILP was 75%, The 2 patients in the pPR groups with a PSR

In the majority of patients with early stage squamous cell cancer (SCC) of the vulva, an inguinofemoral lymphadenectomy is performed (in retrospect) for diagnostic reasons: exclusion of inguinofemoral lymph node metastases. The morbidity of this procedure, however, is significant. The aim of the present study was to evaluate noninvasive detection of inguinofemoral lymph node metastases by positron emission tomography (PET) using L-[1-C-11]-tyrosine (TYR) as tracer. In patients with SCC of the vulva, scheduled for resection of the primary tumor and uni- or bilateral inguinofemoral lymphadenectomy, results of preoperative palpation of the groins and TYR-PET imaging were compared with histopathology. PET imaging was performed using two different methods. In a first group (n = 16), nonattenuation corrected 'whole body' scans were performed, and in a second group (n = 9), attenuation corrected static emission scans. Sensitivity, specificity, accuracy, and positive and negative predictive value for palpation were 62%, 89%, 82%, 67%, and 87% per groin. Sensitivity, specificity, accuracy, and positive and negative predictive value for TYR-PET were calculated for the two methodologies separately and overall. There were no significant differences. Overall values were 53%, 95%, 94%, 33%, and 98% per lymph node and 75%, 62%, 65%, 41% and 88% per groin. Detection of inguinofemoral lymph node metastases by TYR-PET is not superior to palpation. Neither palpation nor TYR-PET is able to adequately predict or exclude presence of inguinofemoral lymph node metastases in patients with SCC of the vulva.

BACKGROUND. The potential of positron emission tomography (PET) with F-18-fluoro-2-deoxy-D-glucose (FDG) to detect primary tumors after unsuccessful conventional diagnostic workup was assessed in patients with metastatic disease from an unknown primary tumor. METHODS. Twenty-nine patients with various histologic types of metastases from an unknown primary site were studied after unsuccessful conventional diagnostic workup. The patients received 370 megabecquerels (MBq) (10 millicuries) FDG intravenously and whole body scans were made after 30 minutes after injection onward. RESULTS, All but one known metastatic tumor sites were visualized. Additional metastases were discovered in five patients. With FDG-PET the primary tumor was identified in 7 patients (24%): in 2 patients with carcinoma of the nasopharynx, in I patient with plasmacytoma of the base of the tongue, in 1 patient with carcinoma of the lung, in 1 patient with carcinoma of the colon, and in 2 patients with breast carcinoma. FDG-PET did not identify a primary tumor in the remaining 22 patients (76%). Despite a negative PET study, the primary lesion was identified in a later phase in 3 of these patients (14%). Survival was not altered by discovery of the primary tumor. CONCLUSIONS. A previously unknown primary turner was able to be identified with FDG-PET in 7 of 29 patients after an unsuccessful conventional diagnostic workup. However, the clinical relevance of PET information in this setting is limited. (C) 1998 American Cancer Society.

To validate the protein synthesis rate (PSR) measured in human brain tumors using L-[1-C-11]tyrosine (TYR) PET, the PSR was compared to histopathological parameters that reflect proliferation and protein synthesis. Methods: We studied 20 patients who had a brain biopsy and who also underwent a PET study with TYR. Paraffin sections were stained with the monoclonal antibody MIB 1, targeted against the core antigen Ki-67, and nucleolar organizer regions (NORs) were measured as argyrophilic NORs (AgNORs). The TYR uptake was measured by PET, and with a kinetic model, the PSR was determined. Results: PSR (nmol/ml/min) ranged from 0.44 to 1.99 (mean, 0.97), Ki-67 labeling indices (%) ranged from 0.9 to 33.5 (mean, 9.5) and AgNOR area (mm(2)/cm(2)) ranged from 0.13 to 0.85. No relationship was found between PSR and Ki-67 labeling index or AgNOR area. Conclusion: It seems that the PSR and proliferation, as measured by Ki-67, are independent processes. The role of the PSR is uncertain, but it is likely that it can be seen as a marker for the homeostasis of the cell.

The aims of the study were to compare the value of L-[1-C-11]tyrosine (TYR) and [F-18]fluoro-2-deoxy-D-glucose (FDG) as tumor tracers in patients with breast cancer, to investigate the correlation between quantitative values and standardized uptake values (SUVs) and to estimate the value of SUVs for the evaluation of therapy. Methods: Eleven patients with one or more malignant breast lesions and two patients with one or more benign breast tumors were studied with TYR and FDG. Doses of 300 MBq of TYR and 230 MBq of FDG were given intravenously. All PET sessions were performed using a Siemens ECAT 951/31 camera. Of 10 malignant tumors and the 3 benign lesions, glucose consumption and protein synthesis rate were quantified. All lesions were studied using SUVs based on body weight, body surface area and lean body mass, with and without correction for plasma glucose or tyrosine levels. Results: All malignant tumors were visualized with both FDG and TYR, but the visual contrast was better with FDG, Increased uptake of the tracers was seen in patients with fibrocystic tissue and complicated the visual assessment and the outlining of tumor tissue. Uptake in fibrocystic disease was more prominent with FDG than with TYR. No difference in tumor/nontumor ratio between the two tracers could be established. FDG showed a false-positive result in one benign lesion. No major differences between the SUVs as defined above were found, although the best correlation between glucose consumption and the SUV was observed when the SUV was based on body surface area and corrected for plasma glucose level (r = 0.85-0.87). The SUV based on lean body mass was found to correlate best with protein synthesis rate (r = 0.83-0.94). Conclusion: in this group of patients, TYR appears to be a better tracer than FDG for breast cancer imaging, because of lower uptake in fibrocystic disease, SUVs correlate well with quantitative values, but future studies must determine whether treatment evaluation is also reliable with SUVs.

We studied the potential of PET with L-[1-C-11]-tyrosine (TYR) to visualize tumors outside the central nervous system and to quantify their protein synthesis rates (PSRs). Methods: Twenty-two patients suspected of having a malignant tumor underwent a PET study with TYR before biopsy, The PSR in nanomoles per milliliter tumor tissue per minute as well as the PSR in contralateral normal tissue, standardized uptake values (SUVs) and tumor-to-nontumor-ratios (T/N ratios) were calculated. Results: Fifteen of the 16 malignancies (94%) were correctly visualized as a hot spot. A chondrosarcoma of the sacrum was not visualized. Of the six patients with benign lesions, cold spots were correctly identified in four (67%), A benign schwannoma and an intramuscular hemangioma of the forearm were visualized as hot spots. PSR in tumor tissue was higher than in the corresponding contralateral normal tissues. PSR and SUV in malignant tumors were higher than in benign tumors. Conclusion: TYR appears to be a good tracer for imaging malignancies. The PSR, which was higher in malignant tumors than in normal tissue and the studied benign lesions, could be quantified and correlated with the SUV.

After acute cerebral stroke, the (peri-) infarct tissue is characterized by calcium (Ca)-mediated neuronal damage and inflammatory processes. Monitoring Ca-mediated damage using the isotope cobalt-55 (Go) as a Ga-tracer may enable PET-imaging of this tissue. Since the fate of (peri-) infarct tissue determines clinical outcome, Go-PET may have prognostic value in stroke. Six stroke patients were examined with Go-PET, MRI and a middle cerebral artery (mca) stroke scale (Orgogozo). In every patient? specific Go-accumulation in the appropriate brain region was seen, irrespective of the integrity of the blood-brain barrier. This pilot study suggests Go-PET as a diagnostic tool in stroke, which may provide additional information on the clinical outcome. Validation of method in larger patient series is necessary. (C) 1997 Elsevier Science B.V.

Background: It is often difficult to detect a local recurrence of soft-tissue sarcomas due to disturbance of the normal anatomy by previous surgery and radiotherapy. The aim of this study was to assess the value of positron emission tomography (PET) with [F-18]fluoro3-deoxy-D-glucose (FDG) for detecting local recurrences. Methods: In the period 1992-1995, 17 patients with proven or suspected local recurrence of soft-tissue sarcoma were examined using FDG-PET. Fifteen of these patients were ultimately proven to have a recurrence. Results: Recurrence was visualized in 14 patients (93%). Small tumors (maximum diameter 0.5 cm) were as easily visible as large lesions (maximum diameter 20 cm). In one patient the PET scan was positive, but the recurrence could not be proven histologically. Recurrence was proven 1 year later. A recurrent low-grade liposarcoma was not visualized. The two patients with benign lesions had a negative PET scan. The mean glucose metabolic rate was calculated to be 13.2 mu mol/100 g/min (range 1.9-28.4). A correlation was found between the histological malignancy grade and the metabolic rate (p

The uptake of L-1-[C-11]-tyrosine (TYR) in cervical lymph nodes of eleven patients with squamous-cell carcinoma (SCC) of the oral cavity was studied with PET to detect lymphogenic metastases. Methods: The TYR-PET results were compared with clinical, MRI, CT, histopathologic findings and historical data of patients studied with FDG. Sensitivity, specificity, accuracy and the positive and negative predictive values were calculated. Results: TYR-PET had sensitivity of 83% and a specificity of 95%, In contrast, the sensitivity and specificity for MRI were 33% and 96%, respectively. The sensitivity and specificity for CT were 55% and 91%, respectively, TYR-PET results compared favorably with FDG. Conclusion: With NR-PET, SCC metastases of the oral cavity can be visualized with high sensitivity and specificity, TYR-PET can be an additional tool for further evaluation of neck malignancies.

We investigated FDG-PET in patients undergoing hyperthermic isolated limb perfusion (HILP) with rTNF-alpha, rIFN-gamma and melphalan for locally advanced soft-tissue sarcoma of the extremities. Methods: Twenty patients (11 women, 9 men; aged 18-80 yr, mean age 49 yr) were studied, FDG-PET studies were performed before, 2 and 8 wk after HILP. After the final PET study, the tumor was resected and pathologically graded, Patients with pathologically complete response (pCR) showed no viable tumor after treatment, Those with pathologically partial response (pPR) showed various amounts of viable tumor in the resected specimens. Results Seven patients showed a pCR (35%) and 12 patients showed a pPR (60%). In one patient, pathological examination was not performed (5%). The pre-perfusion glucose consumption in the pCR group was significantly higher than in the pPR group (p

PET with F-18-fluoro-2-deoxy-D-glucose (FDG) was used to study soft-tissue lesions, The goals of the study were to establish FDG uptake in soft-tissue sarcoma, to determine the sensitivity of this technique, to investigate the correlation between histologic grade and glucose consumption and to determine whether FDG-PET can discriminate between benign and malignant lesions, Methods: PET imaging was performed in 18 patients with soft-tissue sarcoma and 4 patients with a benign soft-tissue lesion. Glucose consumption in the tumors was calculated using Patlak's graphical analysis with an assumption made for the lumped constant. Standardized uptake values also were calculated. Results: All soft-tissue sarcomas were clearly depicted, The median glucose consumption was 13.0 mu mole/100 g/min (range 2.9-41.8 mu mole/100 g/min). A correlation was found between glucose metabolism and the histopathologic malignancy grade, Such a correlation was not demonstrated for the standardized uptake values, One benign lesion was also visualized. Benign lesions were not visualized in two patients and in the remaining patient an equivocal scan was obtained, Benign lesions could be distinguished from high-grade malignant lesions but not consistently from lesions with low or intermediate malignancy grades, Conclusion: PET with FDG is an effective technique to visualize soft-tissue sarcomas. We found a sensitivity of 100%, There is a correlation between glucose metabolic rate and tumor malignancy grade. FDG appears to be unsuitable for discriminating benign lesions from soft-tissue sarcomas with low or intermediate malignancy grades.

The posterolateral defect is a common artifact seen when static N-13-ammonia imaging with PET is used to assess myocardial perfusion. The aim of this study was to compare dynamic and static N-13-ammonia PET and to obtain more insight into the cause of the posterolateral defect. Methods: Dynamic N-13-ammonia PET was performed in 19 healthy nonsmoking volunteers at rest. Perfusion was assessed in the early phase of the study using a curve fit method over the first 90 sec. Nitrogen-13 accumulation (static PET) was assessed 4 to 8 min after injection. Each study was normalized to a mean of 100. The average distribution of normalized perfusion and activity was calculated in 24 segments. Heterogeneity of both activity and perfusion distribution were assessed and the activity distribution was compared with perfusion distribution. Results: Perfusion distribution was homogeneous, with the exception of the inferior and apical regions. Activity distribution was inhomogeneous, with a lower activity in the posterolateral and apical regions. In the whole left ventricle, significant differences in distribution were found between static and dynamic imaging. Conclusion: Perfusion distribution was significantly different on dynamic images compared to static images. The posterolateral defect was not found on dynamic images. The posterolateral defect and other inhomogeneities in activity distribution are caused by tracer-dependent features, probably a redistribution of metabolites of N-13-ammonia.

We describe two similar patients with a clinical diagnosis of corticobasal ganglionic degeneration (CBGD). After a period of increased action tremor, both patients developed a fixed posture in the right arm with a slow rhythmic myoclonus, which appeared to be caused by trains of highly synchronized and stimulus sensitive myoclonic discharges. Resetting of the spontaneous myoclonic discharges by peripheral and central stimulation and a jerk-locked cortical potential were demonstrated in one case. The somatosensory evoked potentials (SEPs) showed abnormal parietal curves with small N20-P25 amplitudes and without giant SEP characteristics. The latencies of the cortical event and of the late responses, and the duration and distribution of the discharges compare best with those of the cortical reflex type of myoclonus. Localized parietal cortical damage, as indicated by clinical evidence and imaging techniques, may well explain the absence of a giant SEP in these patients with CBGD.

The uptake of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) in neck lymph nodes of twelve patients with a squamous-cell carcinoma of the oral cavity was studied with PET in order to detect and locate lymphogenic metastases. Methods: The results of FDG-PET imaging were compared with clinical, MRI and histopathologic findings. Standardized uptake values (SUV) were also calculated. Results: A sensitivity of 91% and a specificity of 88% were calculated for FDG-PET. In contrast, a sensitivity of 36% and a specificity of 94% were calculated for MRI. Calculated SUVs for reactive lymph nodes, metastatic lymph nodes and the primary tumor were undifferentiated. Conclusion: Using FDG-PET, lymph node metastases of squamous-cell carcinomas of the oral cavity can be visualized with a high sensitivity and specificity. FDG-PET can be an improvement in the evaluation of the neck.

Methods: The treatment of a patient with soft-tissue sarcoma was evaluated with FDG-PET. A limb-saving complete remission of a locally advanced liposarcoma of the left thigh was achieved with isolated regional perfusion of the limb with tumor necrosis factor alpha, interferon gamma and melphalan. Results: PET with F-18-FDG before perfusion showed high glucose consumption in the tumor. After perfusion, glucose metabolism in the tumor was absent. Subsequent excision confirmed complete necrosis of the tumor. Conclusion: FDG-PET may be useful in evaluating the results of isolateral regional limb perfusion for soft-tissue sarcomas.

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-C-11]-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 C-11-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 C-11-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 C-11-TYR PET to quantify activity before treatment.