Imaging proliferation in vivo with [F-18]FLT and positron emission tomography.

Positron emission tomography (PET) is now regularly used in the diagnosis and staging of cancer. These uses and its ability to monitor treatment response would be aided by the development of imaging agents that can be used to measure tissue and tumor proliferation. We have developed and tested [F-18]FLT (3'-deoxy-3'-fluorothymidine); it is resistant to degradation, is retained in proliferating tissues by the action of thymidine kinase 1 (TK), and produces high-contrast images of normal marrow and tumors in canine and human subjects.

[18F]-FDG-PET in clinical stage I/II non-seminomatous germ cell tumours: results of the German multicentre trial.

PURPOSE: The aim of this study was to determine the predictive values of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in primary staging in patients with newly diagnosed non-seminomatous germ cell tumour (NSGCT) clinical stage I/II. PATIENTS AND METHODS: The hypothesis was that FDG-PET would improve the negative predictive value (NPV) from 70% to 90%, thus requiring a total of 169 patients. All scans underwent visual analysis by a reference team of nuclear medicine physicians. Results were validated by histology following retroperitoneal lymph node dissection. RESULTS: Only 72 of the planned 169 patients were included, due to poor accrual. The prevalence of nodal involvement was 26%. Correct nodal staging by FDG-PET was achieved in 83% compared with correct computed tomography (CT) staging in 71%. CT had a sensitivity and specificity of 41% and 95%, respectively. Positive predictive value (PPV) and NPV were 87% and 67%, respectively. FDG-PET had a sensitivity and specificity of 66% and 98%, respectively. PPV was 95%. The primary end point was not reached, with an NPV of 78%. CONCLUSION: FDG-PET as a primary staging tool for NSGCT yielded only slightly better results than CT. Both methods had a high specificity while false-negative findings were more frequent with CT. FDG-PET is mostly useful as a diagnostic tool in case of questionable CT scan.

[11C]Vinblastine syntheses and preliminary imaging in cancer patients.

PURPOSE: The primary aim of this work was to establish a radiolabeling procedure of vinblastine, a vinca alkaloid widely used in chemotherapy, with the positron-emitter carbon-11 for application in positron-emission-tomography (PET) studies in cancer patients. The optimized reaction conditions were transferred to an automated radiosynthesizer system for the preparation of [11C]vinblastine under GMP conditions for human use. We report about the whole body activity distribution after injection of [11C]vinblastine as well as the pharmacokinetic behavior in selected organs and the tumor in two patients that were investigated with [11C]vinblastine PET before chemotherapy. METHODS: For carbon-11 labeling of vinblastine the reaction conditions were determined with respect to the two possible labeling precursors (i.e. [11C]methyl iodide and [11C]diazomethane), solvent, reaction temperature and reaction time. Both, [11C]diazomethane and [11C]methyl iodide were tested as labeling precursors with the corresponding demethyl compound of vinblastine, i.e. the vinblastine acid and the potassium salt of vinblastine acid. Two patients with renal carcinoma underwent [11C]vinblastine PET before chemotherapy. One patient underwent a second scan during infusion of unlabeled vinblastine at a therapeutic dose. RESULTS: Best results for the labeling procedure were found when methylation was carried out at 100 degrees C within 20 min using 2 mg/mL of the potassium salt of vinblastine acid in DMSO and [11C]methyl iodide as labeling precursor. Based on [11C]methyl iodide starting activity a radiochemical yield of up 53 % [11C]vinblastine was achieved. In addition, the synthesis was transferred to a remotely controlled module for routine GMP conform production for human use. In large scale production runs up to 1 GBq of [11C]vinblastine was obtained ready for injection within 45 min after EOB. In one patient, whole body PET scans 40 min after injection of 112 MBq [11C]vinblastine showed a focally increased [11C]vinblastine uptake and [11C]vinblastine metabolite uptake, respectively in the known metastases, along with a slow but continuous washout during the measurement interval (0-60 min p.i.). Another patient showed no focally increased [11C]vinblastine uptake and [11C]vinblastine metabolite uptake in the tumor, where radioactivity concentration was comparable to that in the blood. In this patient, a second PET scan during infusion of unlabeled vinblastine revealed similar kinetics with a trend towards delayed hepatic metabolism and higher blood and tumor concentrations. Whereas this patient showed a partial response to chemotherapy, the first patient did not, hypothetically due to the observed vinblastine washout from the tumor. CONCLUSIONS: The carbon-11 labeling of vinblastine using [11C]methyl iodide is superior to the method using [11C]diazomethane. A well working automated radiosynthesis was established for the production of [11C]vinblastine for PET-investigations in cancer patients. The individual pharmacokinetic behavior of the chemo-therapeutic agent to the tumor can be assessed with PET, thus, can be considered to be a realistic approach for individualized chemotherapy.

Predictive impact of 2-18fluoro-2-deoxy-D-glucose positron emission tomography for residual postchemotherapy masses in patients with bulky seminoma.

PURPOSE: To establish the predictive potential of 2-18fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) for detecting viable tumor tissue in residual postchemotherapy masses of seminoma patients. PATIENTS AND METHODS: In this prospective multicenter trial, results of FDG PET studies in seminoma patients with postchemotherapy masses > or = 1 cm were correlated with either the histology of the resected lesion or the clinical outcome on follow-up without resection. Negative PET scans of residual lesions that were devoid of viable tumor tissue on resection or disappeared, shrunk, or remained stable in size for at least 2 years were rated as true-negative (TN). Positive scans without histologic or clinical evidence of tumor tissue were classified as false-positive. In patients with histologically positive or progressive lesions, positive PET scans were defined as true-positive (TP) and negative scans, false-negative (FN). RESULTS: Thirty-seven PET scans of 33 patients were assessable at a median follow-up time of 23 months (range, 2 to 46 months). Histologic data were available from nine patients who had undergone resection. Twenty-eight patients were followed-up clinically and radiologically. Twenty-eight scans were TN, eight were TP, and one was FN. All 14 residual lesions more than 3 cm and 22 (96%) of the 23 < or = 3 cm were correctly predicted by FDG PET. The specificity (100%; 95% confidence interval [CI], 87.7% to 100%), sensitivity (89%; 95% CI, 51.7% to 99.7%), positive predictive value (100%), and the negative predictive value (97%) of FDG PET were superior to data obtained by assessing residual tumor size (< or = or > 3 cm). CONCLUSION: FDG PET is a clinically useful predictor of viable tumor in postchemotherapy residuals of pure seminoma, especially those greater than 3 cm.

Rhenium-188 for inhibition of human aortic smooth muscle cell proliferation.

PURPOSE: To evaluate dose-dependent growth-modulating effects of the beta-gamma emitter Rhenium-188 on cultured human aortic smooth muscle cells (haSMC). METHODS AND MATERIALS: HaSMC were plated in 25 cm(2) flasks. Two days after plating, cells were incubated with the Re-188 (beta E(max) 2.12 MeV, tissue range(max) < 10 mm, T(1/2) 17 h) for five days. The doses administered were 0.2 Gy, 1, 4, 6, 8, 16, and 32 Gy. After five days, the radionuclide was removed. Cell growth, cell cycle distribution, and clonogenic activity were analyzed for the following 25 days. RESULTS: The 0.2 and 1 Gy groups did not show relevant growth-inhibiting effects compared to the control groups. The 4 to 32 Gy groups presented dose-dependent growth inhibition, with a complete growth arrest of the 16 and 32 Gy groups. Clonogenic activity of the smooth muscle cell was strongly inhibited from doses > or =8 Gy. Flow cytometry showed a lasting dose-dependent G2/M phase block. CONCLUSION: Smooth muscle cell (SMC) growth can be controlled effectively with Re-188 for at least 25 days after radiation in vitro. As the first four weeks after arterial angioplasty are crucial concerning neointimal formation, Re-188 may be a valuable radionuclide to inhibit restenosis after arterial angioplasty.

Comparison of 18FDG-PET with CT scans in the evaluation of patients with residual and recurrent Hodgkin's lymphoma.

The reliable assessment of residual masses after treatment as well as of new lesions suspected for relapse remains a diagnostic problem in patients with Hodgkin's disease (HD). The current study compares the results obtained by CT scan to FDG-PET imaging in a blind analysis with respect to the viability of residual masses and in case of suspected relapse. Between 1/94 and 10/99, 47 comparisons of PET and corresponding CT scans - 26 comparisons in 24 patients with residual tumors and 21 comparisons in 20 patients with suspected relapse of HD - were evaluated by independent reviewers blinded to he results of each other. Patients with primary diagnosis had been treated within trials of the German HD Trial study group. Relapsed patients received intensified salvage chemotherapy regimens. PET was assessed visually and by quantifying glucose uptake (SUV). Changes in size of tumor lesions as well as contrast medium enhancement served as criteria for assessment by CT scans. Results were validated either by histologic examination of a resected mass or biopsy (n=17) or by a clinical follow-up over 6 months following treatment (n=30). In 26 cases with residual lesions FDG-PET showed an increased tracer uptake in 8, 7 of which were true positive (TP) and 1 false positive (FP). Eighteen cases were classified as being negative (no viable HD), 17 true negative (TN) and 1 FN. In the blinded reading of the corresponding CT scans, 10 cases with residual lesions were considered to contain vital lymphoma (2 TP, 8 FP). Sixteen CT scans were classified as negative (10 TP, 6 FN). The resulting sensitivity and specificity of PET were 87.5% and 94.4% in contrast to only 25% and 56% for CT scans. The positive and negative predictive values of PET and CT scans were 87.5% and 94.4% and 20% and 62.5%, respectively. In patients with suspected relapse, sensitivity and positive predictive value for the diagnosis of the relapse were 100% and 86%, respectively, yielding the same results for both methods. FDG-PET performed in HD patients with residual masses appears to offer important additional information regarding the presence of viable HD in these residual lesions. In patients with suspected relapse of HD, FDG-PET seems not to offer any information over CT scans. Using SUVs is not superior to visual assessment of PET alone.

Value of positron emission tomography for lung cancer staging.

OBJECTIVE: The therapeutic strategy in non-small-cell lung cancer (NSCLC) requires exact staging of tumour invasion (T) as well as differentiation between ipsi- and contralateral lymph node invasion (N1/2 vs N3). [18F]FDG-positron emission tomography (FDG-PET) has been shown to detect invaded N with high accuracy while correct determination of T appears to be unclear. The purpose of this prospective study was to evaluate benefit and necessity of 18FDG-PET as an additive to conventional staging modalities. METHODS: Forty patients with suspected non-small-cell lung cancer (NSCLC) were staged by means of computed tomography (CT), bronchoscopy, mediastinoscopy and bone scintigraphy. Additionally, attenuation corrected FDG-PET of the thorax was performed pre-operatively for analysis of T and N topography. After surgical resection with radical lymphadenectomy T and N staging results of CT and PET were compared with the pathological diagnoses. Specificity, sensitivity, positive predictive value and accuracy of CT and PET were calculated. RESULTS: Twenty three squamous cell carcinomas, 14 adenocarcinomas, and three non-malignant tumours were found. Accuracy of CT-T was 0.75 and of PET-T 0.78; accuracy of CT-N was 0.78 and of PET-N 0.80. By combination of CT-T and PET-T accuracy was 0.88. Combination of CT-N and PET-N yielded an accuracy of 0.90. In two out of three cases, PET correctly determined T0. In two cases non-malignant inflammatory lymph nodes were falsely staged as malignant by PET. CONCLUSIONS: Adequate pre-operative T- and N-staging is possible with both CT and FDG-PET. Accuracy can be improved by combination of CT and FDG-PET. FDG-PET is superior to CT in order to differentiate between malignant and benign tumours. However, acute inflammation can mimic malignant lymph node invasion. FDG-PET is justified as a supporting staging measure in cases presenting unclear differentiation between N2 and N3 after conventional staging and is helpful in cases with unclear cell type of the primary tumour.

A patient with five primary tumours of the aerodigestive tract and the kidney. The Interdisciplinary Tumour Board, Tübingen.

We report the case of a 65-year-old male who developed an oropharyngeal carcinoma, an oesophageal carcinoma and two primary bronchial carcinomas in combination with a renal cell carcinoma as an additional primary entity. By means of an aggressive diagnostic regimen including radiological and nuclear imaging techniques all carcinomas were detected early and could be treated with curative intention.

[Early prediction of treatment response to high-dose chemotherapy in patients with relapsed germ cell tumors using [18F]FDG-PET, CT or MRI, and tumor marker]. / [ ¹8F]FDG-PET, CT/MRT und Tumormarker als prädiktive Indikatoren für das Ansprechen unter Hochdosis-Chemotherapie bei Patienten mit metastasierten Keimzelltumoren.

PURPOSE: To assess the ability of [(18)F]FDG-PET, CT/MRI and serum tumor marker (TM) for the early prediction of response in patients with metastatic germ cell tumors (GCT) undergoing salvage high-dose chemotherapy (HD-CTX). MATERIALS AND METHODS: Before commencement of HD-CTX, 19 patients with metastases from GCT were evaluated with [(18)F]FDG-PET, CT or MRI and TM after 2-3 cycles of induction chemotherapy and the results compared with those of the baseline examinations. PET was analyzed visually and quantitatively by calculating the standard uptake value (SUV). CT or MRI was evaluated for changes in tumor size (progressive disease/stable disease PD/SD = viable lesion; partial remission/complete remission PR/CR = nonviable lesion), density or signal intensity, homogeneity and contrast enhancement. For the prognosis, the worse case, i.e., the most vital lesion detected in a patient, was considered. The reference standard was the result of the histology after resection of any residual masses (N = 10) and/or the clinical-radiological follow-up for at least 6 months after completion of the treatment (N = 9). RESULTS: Six of nineteen patients (32 %) remained progression-free for over 6 months following treatment, whereas 13 (68 %) progressed. The outcome of HD-CTX was correctly predicted by PET, CT and TM in 89 %, 67 % and 88 %, respectively. In 5 of 6 patients with successful HD-CTX, PET was negative (mean SUV = 1.8), with CT or MRI showing a partial regression of the tumor in 4 of 5 patients. Of the 13 patients not cured by HD-CTX, the PET data were positive in all (mean SUV = 2.7), and the CT/MRI results were true positive (PD or SD) in 8 and false negative (PR) in 5 patients. The combined assessment of CT and TM corrected 3 false negative prognoses and 1 false positive CT prognosis. Two patients with unfavorable outcome despite a favorable response by CT and TM criteria were exclusively identified by PET. The resultant sensitivities and specificities for the prediction of therapy response are as follows: PET 100% and 67%; CT/MRI 62% and 80%; TM 83% and 100%; CT+TM 85% and 83%. CONCLUSION: FDG-PET has a high prognostic value for predicting the response to chemotherapy in patients with metastatic GCT early in the course of treatment and may improve patient selection for subsequent HD-CTX protocols. Especially in patients with response to induction chemotherapy according to CT or TM evaluation, PET offers additional information to detect patients with an overall unfavorable outcome.

[Dose-dependent effects of the combined beta/gamma emitter 186-Rhenium on the growth of human vessel wall cells]. / Dosisabhängige Auswirkungen des kombinierten beta/gamma Emitters Rhenium186 auf das Wachstum humaner Gefässwandzellen.

PURPOSE: The aim of this study was to evaluate the capability of human aortic smooth musc e cells (HaSMC) and endothelial cells (EC) to recover after incubation with the combined beta/gamma emitter 186rhenium. MATERIALS AND METHODS: Two days after plating, HaSMC and EC were incubated for five days with 186Re (total doses applied 4 Gy-32 Gy). Cell counts were performed for a period of 30 days (haSMC) and 22 days (EC). To detect possible growth recovery, colony formation assays were plated for both cell types on day 5, 10, and 20 (and lay 30 for haSMC). RESULTS: Both cell types presented a dose-dependent growth inhibition which was maximum at a dose of 32 Gy. Human endothelial cells presented with total growth recovery at 4 and 8 Gy, and a partial growth recovery at 16 Gy. Smooth muscle cells only presented partial growth recovery at 4 and 8 Gy. At 16 Gy and more no recovery was detected. CONCLUSION: HaSMC as well as EC growth can be modulated effectively with 186Re over a period of 30 days in vitro. Compared to smooth muscle cells human endothelial cellls seem to possess a higher potential to recover at doses of 8 to 16 Gy. 186Re may be a valuable radionuclide to prevent restenosis.

[MRI and oncoscintigraphy with 99m-Tc-MIBI in the follow up of thyroid cancer]. / KST und Onkoszintigraphie mit 99mTc-MIBI in der Nachsorge des Schilddrüsenkarzinoms.

Magnetic resonance imaging (MRI) and 99mTc-MIBI oncoscintigraphy are new procedures for the detection of recurrent differentiated thyroid cancer. We evaluated the utility of both techniques compared to ultrasonography, radioiodine scanning, and measurement of serum thyroglobulin in patients with (n = 21) or without suspicion (n = 34) of tumor relapse. Although MRI was most effective in detecting local recurrencies (sensitivity: 100%), additional diagnostic information was only obtained in patients with mediastinal lesions. On the other hand, oncoscintigraphy was less sensitive (67%) but highly specific in differentiating reactive lymph node enlargement from metastatic disease (specificity: 93.5%). Oncoscintigraphy may be used instead of radioiodine scanning in patients with doubtful lymph node findings and spare them withdrawal of TSH-suppressive hormone medication. Routine estimation of serum thyroglobulin proved to be highly efficient in screening for tumor relapse using a cut-off level of 3 ng/ml (accuracy: 100%).

[Determination of factors affecting the therapeutic outcome of radioiodine therapy in patients with Graves' disease]. / Bestimmung von Einflussgrössen für den Therapieerfolg der Radioiodtherapie bei Patienten mit Morbus Basedow.

AIM: Of this study was to determine whether success of radioiodine therapy (RIT) in Graves' disease depends on thyroid volume, function, thyroideal receptor antibodies (TRAK), thyreostasis, therapeutic dosage, 131I uptake, or effective half-life. METHOD: 78 patients received an average of 626 +/- 251 MBq of iodine-131 orally for thyroid ablation. 60 were assessed for successful therapy 3 months after RIT. RESULTS: In patients showing hyperthyreosis or a TRAK value > 11 U/l at the beginning of RIT, a significantly lower therapeutic dosage and effective iodine half-life were found than in non-hyperthyreotic patients or patients with TRAK < or = 11 U/l. Patients with a thyroid volume < or = 25 ml showed a significantly lower 131I uptake, but a significantly higher relative uptake (131I uptake/ volume) than patients with a thyroid volume > 25 ml. All failures were treated thyreostatically during RIT and showed a significantly lower therapeutic iodine dosage and relative uptake, as well as a significantly higher thyroid volume than patients with a successful therapy. RIT caused a thyroid volume reduction of 44%, with therapy failures showing a significantly lower volume reduction. Patients who received a therapeutic dosage of < or = 250 Gy showed significantly worse results than did those who had received > 250 Gy. Only one case of therapy failure received a dosage > 250 Gy, while 50% of failures received dosages > 200 Gy but < 250 Gy. Multivariate analyses (MANOVA, factor analyses) showed thyreostasis as the decisive negative factor for a successful course of therapy. CONCLUSIONS: Since most treatment failures occurred in patients under thyreostatic medication we recommend raising the target dosage to 250 Gy for these cases.

[Chemiluminescence of alveolar macrophages in pneumonia]. / Chemilumineszenz von Alveolarmakrophagen bei Pneumonie.

Chemiluminescence of alveolar macrophages was examined in 45 patients with and without immunodeficiency. Some of these patients were suffering from pneumonia. Chemiluminescence was reduced in patients with immunosuppression compared to those with normal immunofunction. Although this parameter of macrophage function was on the whole increased in pneumonia, the patients with a weak immunodefense presented with a markedly reduced increase in chemiluminescence. This explains why opportunistic infections occur in such numbers if there is an immunodeficiency.

[Bone marrow recovery after irradiation of the spine]. / Knochenmarkregeneration nach Bestrahlung der Wirbelsäule.

BACKGROUND: Imaging of bone marrow by radio labeled antibodies against NCA-95 antigen of human granulocytes offers the possibility to visualize granulopoietic activity. After radiotherapy, a reduced uptake delineates the radiation field. Aim of our investigation was the study of strength and duration of this effect. PATIENTS AND METHODS: We analyzed 80 cases of patients irradiated for different primary or metastatic malignancies including parts of the spine who received a bone marrow scan for re-staging or during follow-up. Activity uptake of vertebrae inside and outside the irradiation portal was evaluated by ROI and the ratio was taken as measure of bone marrow suppression. RESULTS: A depression of granulopoietic bone marrow activity was seen even after a few fractions of 1.8 or 2 Gy (Figure 1). Depending on time since irradiation (Figure 2), we found a bone marrow recovery. In patients without bone metastasis, regeneration could be complete, whereas in patients treated for metastases, it was incomplete in all cases (Figure 3). CONCLUSIONS: For a certain time after irradiation, radioimmunoimaging delineates the irradiation portal by showing depression of granulopoiesis. Later on, it also shows bone marrow regeneration after radiotherapy. This may be helpful in reconstruction of radiation portals or in toxicity estimation during multimodal cancer therapy.

[Results of positron emission tomography with fluorine-18 labeled fluorodeoxyglucose in differential diagnosis and staging of pancreatic carcinoma]. / Ergebnisse der Positronenemissionstomographie mit Fluor-18-markierter Fluordesoxyglukose bei Differentialdiagnose und Staging des Pankreaskarzinoms.

Although the detection of pancreatic carcinoma has been considerably improved by recently developed imaging procedures, differential diagnosis between cancer and benign tumor masses, as well as lymph node staging, is still difficult. In vivo evaluation of regional glucose metabolism by means of positron emission tomography (PET) and fluorine-18-labelled fluorode-oxyglucose (FDG) is a new approach utilizing metabolic instead of morphological tumor properties for diagnosis. PATIENTS AND METHODS. A total of 85 patients with suspected pancreatic carcinoma were investigated by FDG-PET prior to surgery. Static PET scans were evaluated visually as well as quantitatively, taking increased FDG uptake as a sign of malignancy. PET results were correlated with intraoperative findings and histopathology of surgical specimens. RESULTS. Forty-seven out of 55 (85%) malignant tumors and 23 out of 30 (77%) benign lesions were correctly classified by PET. Lymph node metastases were present in 31 patients, 19 of them (61%) positive in PET. In 7 our of 13 (54%) patients with liver metastases, PET detected hypermetabolic lesions. False-negative findings were mainly due to disturbance of glucose metabolism in diabetic patients, while most false-positive results could be attributed to acute inflammatory lesions in chronic pancreatitis. CONCLUSIONS. Our results indicate that classification of pancreatic masses can be improved by use of FDG-PET, which might lead to a reduction of unnecessary laparotomies in patients with benign or incurable disease.

Non-invasive assessment of distribution volume ratios and binding potential: tissue heterogeneity and interindividually averaged time-activity curves.

Due to the stochastic nature of radioactive decay, any measurement of radioactivity concentration requires spatial averaging. In pharmacokinetic analysis of time-activity curves (TAC), such averaging over heterogeneous tissues may introduce a systematic error (heterogeneity error) but may also improve the accuracy and precision of parameter estimation. In addition to spatial averaging (inevitable due to limited scanner resolution and intended in ROI analysis), interindividual averaging may theoretically be beneficial, too. The aim of this study was to investigate the effect of such averaging on the binding potential ( BP) calculated with Logan's non-invasive graphical analysis and the "simplified reference tissue method" (SRTM) proposed by Lammertsma and Hume, on the basis of simulated and measured positron emission tomography data [[(11)C] d- threo-methylphenidate (dMP) and [(11)C]raclopride (RAC) PET]. dMP was not quantified with SRTM since the low k(2) (washout rate constant from the first tissue compartment) introduced a high noise sensitivity. Even for considerably different shapes of TAC (dMP PET in parkinsonian patients and healthy controls, [(11)C]raclopride in patients with and without haloperidol medication) and a high variance in the rate constants (e.g. simulated standard deviation of K(1)=25%), the BP obtained from average TAC was close to the mean BP (error <5%). However, unfavourably distributed parameters, especially a correlated large variance in two or more parameters, may lead to larger errors. In Monte Carlo simulations, interindividual averaging before quantification reduced the variance from the SRTM (beyond a critical signal to noise ratio) and the bias in Logan's method. Interindividual averaging may further increase accuracy when there is an error term in the reference tissue assumption E= DV(2)- DV' ( DV(2) = distribution volume of the first tissue compartment, DV' = distribution volume of the reference tissue). This can be explained by the fact that the distribution volume ratio ( DVR= DV/DV') obtained from averaged TAC is an approximation for Sigma DV/Sigma DV' rather than for Sigma DVR/ n. We conclude that Logan's non-invasive method and SRTM are suitable for heterogeneous tissues and that discussion of group differences in PET studies generally should include qualitative and quantitative assessment of interindividually averaged TAC.

Early prediction of treatment response to high-dose salvage chemotherapy in patients with relapsed germ cell cancer using [(18)F]FDG PET.

To assess the ability of [(18)F]fluorodeoxyglucose positron emission tomography for the early prediction of response in patients with relapsed metastatic germ cell tumours undergoing salvage high-dose chemotherapy. The role of positron emission tomography was compared with established means of tumour response assessment such as CT scans/MRI and serum tumour marker changes. In addition, positron emission tomography was compared with a current prognostic score which differentiates three prognostic groups with failure-free survival rates ranging from 5-50%. [(18)F]fluorodeoxyglucose uptake of metastases from germ cell tumours as well as CT scans and serum tumour marker were acquired after 2-3 cycles of induction chemotherapy but before the start of high-dose chemotherapy and CT scans/serum tumour marker were compared with the baseline examinations in 23 patients with relapsed germ cell tumours. To evaluate the validity of early response prediction by positron emission tomography, radiological monitoring and serum tumour marker decline, histopathologic response after resection of residual masses and/or the clinical course over 6 months after the end of treatment (relapse vs freedom of progression) were used. Overall, 10 patients (43%) achieved a marker-negative partial remission, three (13%) a marker-positive partial remission, five (22%) a disease stabilization and five (22%) progressed during treatment. Nine patients (39%) remained progression-free over 6 months following treatment, whereas 14 (61%) progressed. The outcome of high-dose chemotherapy was correctly predicted by positron emission tomography/CT scan/serum tumour marker in 91/59/48%. Eight patients with a favourably predicted outcome by CT scans plus serum tumour marker but a positive positron emission tomography prior to high-dose chemotherapy, failed treatment. This results in the following sensitivities/specificities for the prediction of failure of high-dose chemotherapy: positron emission tomography 100/78%; radiological monitoring 43/78%; serum tumour marker 15/100%. The positive and negative predictive values of positron emission tomography were 88 and 100%, respectively. As compared with the prognostic score, positron emission tomography was correctly positive in all patients of the three risk groups who failed treatment. In addition, a negative positron emission tomography correctly predicted a favourable outcome in the good and intermediate group. [(18)F]fluorodeoxyglucose positron emission tomography imaging can be used to assess response to chemotherapy in patients with relapsed germ cell tumours early in the course of treatment and may help to identify patients most likely to achieve a favourable response to subsequent high-dose chemotherapy. In patients with response to induction chemotherapy according to CT scans or serum tumour marker evaluation, positron emission tomography seems to add information to detect patients with an overall unfavourable outcome. It may also be a valuable addition to the prognostic model particularly in the good and intermediate group for further selection of patients who will profit from high-dose chemotherapy.

FDG PET for staging of advanced non-small cell lung cancer prior to neoadjuvant radio-chemotherapy.

The aim of this study was to evaluate positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) for the staging of non-small cell lung cancer (NSCLC) before combined neoadjuvant, i.e. preoperative, radio-chemotherapy (RCT). From November 1998 until September 2001, 101 patients with NSCLC were investigated prospectively. The inclusion criterion was a histologically proven NSCLC of stage IIIA or B according to conventional staging including biopsy. The results of PET were compared with those obtained by mediastinoscopy, computed tomography (CT), bone scan and abdominal ultrasonography. Validation of discrepant findings was achieved by biopsy or repeated CT. PET proved to be highly accurate for the detection of lymph node metastases (sensitivity 96%, specificity 73%, positive predictive value 88%, negative predictive value 89%, accuracy 88%) as well as distant metastases (in 25/101 patients, all previously unknown). PET findings changed further treatment in 29/101 patients (29%). Twenty-five were excluded from RCT due to the presence of previously unknown distant metastases. One patient was free of metastases and therefore was operated on without pre-treatment. Two patients did not receive any further treatment because a malignant tumour could be excluded after PET. In the final patient PET demonstrated a tumour pattern not typical for NSCLC which could be attributed to a seminoma after repeated biopsy. FDG PET is the most accurate non-invasive diagnostic procedure for the staging of advanced NSCLC. Therefore use of FDG PET is highly recommended in order to select patients for neoadjuvant or other stage-dependent treatment modalities.