Perspectives on joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards for [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors.

Response assessment in the context of immunomodulatory treatments represents a major challenge for the medical imaging community and requires a multidisciplinary approach with involvement of oncologists, radiologists, and nuclear medicine specialists. There is evolving evidence that [18F]FDG PET/CT is a useful diagnostic modality for this purpose. The clinical indications for, and the principal aspects of its standardization in this context have been detailed in the recently published "Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0". These recommendations arose from a fruitful collaboration between international nuclear medicine societies and experts in cancer treatment. In this perspective, the key elements of the initiative are reported, summarizing the core aspects of the guidelines for radiologists and nuclear medicine physicians. Beyond the previous guidelines, this perspective adds further commentary on how this technology can advance development of novel therapeutic approaches and guide management of individual patients.

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients.

OBJECTIVE: Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET). MATERIALS AND METHODS: The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients' representatives and patients' self-help groups addressing the patients' willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation. RESULTS: (i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio. CONCLUSION: The dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.

The sodium iodide symporter (NIS): novel applications for radionuclide imaging and treatment.

Cloning of the sodium iodide symporter (NIS) 25 years ago has opened an exciting chapter in molecular thyroidology with the characterization of NIS as one of the most powerful theranostic genes and the development of a promising gene therapy strategy based on image-guided selective NIS gene transfer in non-thyroidal tumors followed by application of 131I or alternative radionuclides, such as 188Re and 211At. Over the past two decades, significant progress has been made in the development of the NIS gene therapy concept, from local NIS gene delivery towards promising new applications in disseminated disease, in particular through the use of oncolytic viruses, non-viral polyplexes, and genetically engineered MSCs as highly effective, highly selective and flexible gene delivery vehicles. In addition to allowing the robust therapeutic application of radioiodine in non-thyroid cancer settings, these studies have also been able to take advantage of NIS as a sensitive reporter gene that allows temporal and spatial monitoring of vector biodistribution, replication, and elimination - critically important issues for preclinical development and clinical translation.

Correction to: 18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors.

The article 18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors written by Laure Michaud, B. J. Beattie, T. Akhurst, M. Dunphy, P. Zanzonico, R. Finn, A. Mauguen, H. Schöder, W. A. Weber, A. B. Lassman, R. Blasberg.

18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors.

PURPOSE: The aim of our study was to investigate the efficacy of 18F-Fluciclovine brain PET imaging in recurrent gliomas, and to compare the utility of these images to that of contrast enhanced magnetic resonance imaging (MRI) and to [11C-methyl]-L-methionine (11C-Methionine) PET imaging. We also sought to gain insight into the factors affecting the uptake of 18F-FACBC in both tumors and normal brain, and specifically to evaluate how the uptake in these tissues varied over an extended period of time post injection. METHODS: Twenty-seven patients with recurrent or progressive primary brain tumor (based on clinical and MRI/CT data) were studied using dynamic 18F-Fluciclovine brain imaging for up to 4 h. Of these, 16 patients also had 11C-Methionine brain scans. Visual findings, semi-quantitative analyses and pharmacokinetic modeling of a subset of the 18F-Fluciclovine images was conducted. The information derived from these analyses were compared to data from 11C-Methionine and to contrast-enhanced MRI. RESULTS: 18F-Fluciclovine was positive for all 27 patients, whereas contrast MRI was indeterminate for three patients. Tumor 18F-Fluciclovine SUVmax ranged from 1.5 to 10.5 (average: 4.5 ± 2.3), while 11C-Methionine's tumor SUVmax ranged from 2.2 to 10.2 (average: 5.0 ± 2.2). Image contrast was higher with 18F-Fluciclovine compared to 11C-Methionine (p < 0.0001). This was due to 18F-Fluciclovine's lower background in normal brain tissue (0.5 ± 0.2 compared to 1.3 ± 0.4 for 11C-Methionine). 18F-Fluciclovine uptake in both normal brain and tumors was well described by a simple one-compartment (three-parameter: Vb,k1,k2) model. Normal brain was found to approach transient equilibrium with a half-time that varied greatly, ranging from 1.5 to 8.3 h (mean 2.7 ± 2.3 h), and achieving a consistent final distribution volume averaging 1.4 ± 0.2 ml/cc. Tumors equilibrated more rapidly (t1/2ranging from 4 to 148 min, average 57 ± 51 min), with an average distribution volume of 3.2 ± 1.1 ml/cc. A qualitative comparison showed that the rate of normal brain uptake of 11C-Methionine was much faster than that of 18F-Fluciclovine. CONCLUSION: Tumor uptake of 18F-Fluciclovine correlated well with the established brain tumor imaging agent 11C-Methionine but provided significantly higher image contrast. 18F-Fluciclovine may be particularly useful when the contrast MRI is non-diagnostic. Based on the data gathered, we were unable to determine whether Fluciclovine uptake was due solely to recurrent tumor or if inflammation or other processes also contributed.

The EANM practice guidelines for bone scintigraphy.

PURPOSE: The radionuclide bone scan is the cornerstone of skeletal nuclear medicine imaging. Bone scintigraphy is a highly sensitive diagnostic nuclear medicine imaging technique that uses a radiotracer to evaluate the distribution of active bone formation in the skeleton related to malignant and benign disease, as well as physiological processes. METHODS: The European Association of Nuclear Medicine (EANM) has written and approved these guidelines to promote the use of nuclear medicine procedures of high quality. CONCLUSION: The present guidelines offer assistance to nuclear medicine practitioners in optimizing the diagnostic procedure and interpreting bone scintigraphy. These guidelines describe the protocols that are currently accepted and used routinely, but do not include all existing procedures. They should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary.

What is the clinical value of PET/CT in the diagnosis of pulmonary nodules?

The noninvasive diagnostic workup of solitary pulmonary nodules (SPNs) continues to be a challenge for radiologists and nuclear medicine physicians. Morphological evaluation is useful to differentiate between benign and malignant SPNs, but there is a considerable overlap between the benign and the malignant features, resulting in a large fraction of morphologically indeterminate SPNs. Integrated PET/CT with the glucose analogue 18F-fluorodeoxyglucose (FDG PET/CT) can simultaneously evaluate morphological characteristics, anatomic location and metabolic status of SPNs. FDG PET/CT has been shown to result in an overall improved accuracy for the detection of malignant SPNs. In addition, it is the most accurate technique for the staging of malignant SPNs. On the other hand, there are many causes for false positive or false negative FDG PET/CTs. Therefore, FDG PET/CT cannot replace histological evaluation of SPNs, but can be clinically helpful in specific subgroups of patients with SPNs. The goal of this review is to provide an overview of the literature on PET/CT imaging in SPNs and to describe several clinical scenarios for the use of FDG PET/CT in SPNs.

Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity.

BACKGROUND: Stereotactic ablative body radiotherapy (SBRT, SABR) is being increasingly applied because of its high local efficacy, e.g., for small lung tumors. However, the optimum dosage is still under discussion. Here, we report data on 45 lung lesions [non-small cell lung cancer (NSCLC) or metastases] in 39 patients treated between 2009 and 2010 by SABR. PATIENTS AND METHODS: SABR was performed with total doses of 35 Gy (5 fractions) or 37.5 Gy (3 fractions) prescribed to the 60% isodose line encompassing the planning target volume. Three-monthly follow-up CT scans were supplemented by FDG-PET/CT if clinically indicated. RESULTS: The median follow-up was 17 months. Local progression-free survival rates were 90.5% (all patients), 95.0% (NSCLC), and 81.8% (metastases) at 1 year. At 2 years, the respective local progression-free survival rates were 80.5%, 95.0%, and 59.7%. Overall survival rates were 71.1% (all patients), 65.4% (NSCLC), and 83.3% (metastases) at 1 year. Overall survival rates at 2 years were 52.7%, 45.9%, and 66.7%, respectively. Acute side effects were mild. CONCLUSION: With the moderate dose schedule used, well-tolerated SABR led to favorable local tumor control as in other published series. Standardization in reporting the dose prescription for SABR is needed to allow comparison of different series in order to determine optimum dosage.

PET and SPECT for radiation treatment planning.

Positron emission tomography (PET) and single photon computed emission tomography (SPECT) have been evaluated in several studies for radiation treatment planning in patients with primary brain tumors. PET with the glucose analogue fluorodeoxyglucose has been found to be of limited use for radiation treatment planning because the high physiologic glucose use of normal gray matter makes delineation of tumors challenging. In contrast, there is considerable evidence that PET or SPECT with radiolabeled amino acid or amino acid analogues provides valuable information for the delineation of gliomas. Increased amino acid uptake has been found to be a more specific marker for viable tumor tissue than signal abnormalities on MRI. In addition, increased amino acid uptake is frequently observed in tumor areas that have not caused a disruption of the blood brain barrier. Therefore, PET and SPECT with radiolabeled amino acids provide a unique opportunity to visualize the infiltrative growth of gliomas and use this information for radiation treatment planning.

[German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids]. / PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren.

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.

[Graves' ophthalmopathy from the internist's perspective]. / Endokrine Orbitopathie aus internistischer Sicht.

Graves' orbitopathy (GO) is the most frequently observed extrathyroidal manifestation of Graves' disease occurring in up to 40% of patients. Most patients with Graves' orbitopathy are tested positive for TSH receptor autoantibodies (TRAb), which are pathognomonic for Graves' disease and also play a central pathogenetic role in the development of GO. For the diagnosis of Graves' disease, symptoms of hyperthyroidism, low TSH and high fT3 and/or fT4 levels and positive TRAbs are typical. All patients with Graves' disease must be regularly examined for extrathyroidal manifestations, especially for Graves' orbitopathy. For hyperthyroidism, treatment with antithyroidal drugs, such as thiamazole or propylthiouracil is initiated to quickly restore euthyroidism, which also frequently leads to improvement of Graves' orbitopathy. Smoking cessation is also heavily mandated. In cases of relapse or ineffective antithyroidal treatment, radioiodine therapy or thyroid surgery is a further definitive therapeutic option to treat hyperthyroidism. The management of Graves' orbitopathy remains clinically challenging and demands involvement of a multidisciplinary team including endocrinologists, ophthalmologists, surgeons, radiotherapists and nuclear medicine specialists.

[Molecular imaging in cancer therapy]. / Molekulare Bildgebung in der Tumortherapie.

Targeted drugs that modulate the function of specific molecules in diseased tissues hold great promise for the treatment of many diseases, including malignant tumors. However, there are several challenges for the efficient evaluation of these drugs in clinical trials as well as for the use in clinical practice. These include (i) the selection of patients likely to benefit from treatment with a specific targeted drug, (ii) finding the right dose and dose schedule, (iii) monitoring target inhibition, and (iv) assessing tumor response to therapy. Standard anatomic imaging continues to play an important role for addressing these challenges, but molecular imaging provides several new opportunities to make the use of targeted drugs more efficient. Using molecular imaging, the expression of drug targets can be assessed noninvasively, the concentration of drugs can be measured in the tumor tissue, target inhibition can be monitored, and tumor response to therapy can be evaluated earlier than with anatomic imaging techniques. Therefore, it is expected that molecular imaging will play an increasing role for guiding molecularly defined therapeutic interventions.

[Demonstration of angiogenesis and the effect on an antiangiogenetic therapy with 99mTc labeled erythrocytes]. / Darstellung der Angiogenese und der Effekte einer antiangiogenetischen Therapie mit 99mTc-markierten Erythrozyten.

AIM: To evaluate, whether scintigraphic studies with radiolabeled erythrocytes may be used to demonstrate the formation of new vessels during angiogenesis and if an effect on antiangiogenetic therapy could be detected. METHODS: As an angiogenesis model we used the ingrowth of blood vessels in matrigel, subcutaneously injected into mice. In order to measure the relative blood volume in the matrigel non-invasively, mouse erythrocytes were labeled with Technetium-99m DTPA. The amount of activity in the matrigel was measured 30 minutes after injection of the radiolabeled erythrocytes with a gammacamera (in-vivo) and a gammacounter (ex-vivo). These results were correlated with the concentration of hemoglobin in the matrigel and the immunhistochemically evaluated density of blood vessels. The influence of the angiogenesis stimulating growth factor (bFGF) and the antiangiogenetic effect of the cyclooxigenase type 2 inhibitor (COX-2) NS398 were tested. RESULTS: There was a close correlation between the activity concentration in the matrigel and the hemoglobin content. Treatment with bFGF significantly increased the activity concentration from 1.74% +/- ID/g to 4.06% +/- 0.36 (p < 0.01), whereas treatment with NS398 significantly inhibited tracer uptake from 2.83% ID/g +/- 0.33 to 0.87% ID/g +/- 0.12 (p < 0.01). CONCLUSION: These results demonstrate the feasibility of using (99m)Tc labelled erythrocytes for scintigraphic imaging to assess the effects of angiogenesis stimulating and inhibiting interventions non-invasively.

Visualisation of metastatic oesophageal and gastric cancer and prediction of clinical response to palliative chemotherapy using 18FDG PET.

AIM: This study assessed the value of (18)F-deoxyglucose positron emission tomography (FDG-PET) for visualisation and early metabolic response assessment in metastatic gastro-oesophageal cancer. PATIENTS, METHODS: Twenty-six patients who were treated for metastatic disease (20 adenocarcinomas, 6 squamous cell cancers) underwent FDG-PET before and two weeks after the onset of palliative chemotherapy with either oxaliplatin + 5-FU/LV or with docetaxel + capecitabine. PET results were validated according to clinical response based on RECIST criteria. RESULTS: Twenty-four tumours (92%) could be visualised by FDG-PET and were also assessable by a second PET scan at 2 weeks. The 2 tumours that were not detectable by PET were both gastric cancers belonging to the non-intestinal subtype according to Lauren. Median time to progression and overall survival were not significantly different for metabolic responders and non-responders (6.3 vs 5.3 months and 14.1 vs 12.5 months, respectively). CONCLUSION: In this heterogeneous study population, FDG-PET had a limited accuracy in predicting clinical response. However, the metabolic response prediction was particularly good in the subgroup of patients with oesophageal squamous cell cancer. Therefore, FDG-PET and assessment of cancer therapy clearly merits further investigation in circumscribed patient populations with metastatic disease.

11C-Methionine positron emission tomography for preoperative evaluation of suggestive low-grade gliomas.

OBJECTIVE: The treatment regimen for cerebral gliomas is different, depending on the histological grade of the lesion. The therapeutic strategy for anaplastic gliomas and glioblastomas is more aggressive, including microsurgical removal, radiation and chemotherapy. The management for low-grade gliomas is still under discussion, operation or "wait and see" tactics are possible options. Therefore the diagnostic imaging procedures are crucial for further treatment planning. Although most of the low-grade gliomas appear as hypointense lesions without contrast medium (CM) enhancement on magnetic resonance images, in some cases lesions without CM enhancement can be anaplastic tumours as well. 11C-Methionine positron emission tomography (MET-PET) was performed for preoperative evaluation of non or low CM enhancing intracerebral lesions, so-called suggestive low-grade gliomas. METHOD: 20 patients harbouring suggestive low-grade gliomas were included. Seventeen patients were found to be candidates for open surgery and 3 patients were planned for stereotactic biopsy due to the localisation of the lesions. MET-PET studies were performed a few days prior to surgery. On the day of surgery MRI sequences for neuronavigation planning were carried out (MPRAGE and FLAIR sequences). All image data were fused for operation with neuronavigation-guided microsurgery or stereotactic biopsy (BrainLAB Neuronavigation system, VectorVision 6.1). Biopsies were taken from the MET uptake areas as well as from areas without MET uptake. RESULTS: 2/20 patients showed sparse CM enhancement on MRI T (1) images, 18/20 patients had lesions without CM enhancement. MET uptake was found in 16/20 cases (T/N ratio 1.5 or more) and no MET uptake was documented in 4/20 cases (T/N ratio <1.5). Histologically the 2 patients with sparse CM enhancement and MET uptake were glioblastoma multiforme, 10/14 patients with MET uptake and without CM enhancement had an anaplastic astrocytoma WHO III, 3/14 with MET uptake and no CM enhancement had an anaplastic oligoastrocytoma WHO III, and 1/14 had an oligoastrocytoma grade II. The lesions of the 4 patients without MET uptake and without CM enhancement were classified as astrocytoma grade II in 2 cases, as astrocytoma grade I in 1 case and as astrocytoma III in one case. CONCLUSION: According to the results of this study, we find MET-PET to be a helpful tool for pretreatment evaluation of non-CM enhancing, suggestive low-grade intracerebral lesions. MET-PET adds valuable information for the decision-making for surgery or stereotactic biopsy.

FDG PET and CT in locally advanced adenocarcinomas of the distal oesophagus. Clinical relevance of a discordant PET finding.

AIM: The incidence of adenocarcinomas of the distal oesophagus (ADE) has dramatically increased in Western countries. The clinical importance of a FDG PET finding discordant with CT was determined in patients with locally advanced ADE. In addition, tumour standardized uptake values (SUV) were correlated with patient survival. PATIENTS, METHODS: 40 consecutive patients were analyzed retrospectively. All patients underwent an attenuation corrected FDG PET scan (neck, chest, abdomen) and contrast enhanced helical CT of the chest and abdomen. PET and CT scans were reviewed independently and concomitantly with respect to metastases in predefined lymph node sites and organs. Any discordance between PET and CT was assessed for clinical relevance. Clinical relevance was defined as a change in the overall therapeutic concept (curative vs. palliative). Follow-up imaging and histological evaluation served as the gold standard. Mean tumour SUVs were determined by 1.5 cm regions of interest placed over the tumour's maximum. RESULTS: When read independently from the CT scan FDG PET indicated a clinically relevant change in tumour stage in 9/40 patients (23%) and a non-relevant change in 11/40 patients (28%). PET was correct in 5/9 patients (56%) with clinically relevant discordances. In 4/9 patients PET was incorrect (3 false positive due to suspicion of M1-lymph nodes or lung metastases, 1 false negative in disseminated liver metastases). With concomitant reading, PET indicated a clinically relevant change in tumour stage in 6/40 patients (15%) and a non-relevant change in 5/40 patients (13%). PET was correct in 5/6 patients (83%) with clinically relevant discordances. The patient with disseminated liver disease remained the single false negative. Overall, the benefit from PET was based on its higher diagnostic accuracy at organ sites. Tumour SUV did not correlate with patient survival. CONCLUSION: About half of discordances between FDG PET and CT are clinically relevant. Concomitant reading of PET and CT is advisable as it reduces the overall rate of discordances and enhances the accuracy of PET in clinical relevant discordances (from 56% to 83%).

Comparison of different SUV-based methods for monitoring cytotoxic therapy with FDG PET.

PURPOSE: Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is a promising tool for monitoring cytotoxic therapy in tumours. Due to the limited data available, a standard imaging protocol for the prediction of tumour response has not yet been approved. The aim of this study was to compare commonly applied imaging protocols and calculations of the standardised uptake value (SUV) for the early prediction of histopathological response to chemotherapy. METHODS: Serial FDG PET scans of 43 patients with gastric carcinomas were retrospectively analysed. All patients received two consecutive scans (one bed position at 40 min p.i. and four bed positions at 90 min p.i.) at baseline and during the first cycle of cisplatinum-based chemotherapy. Reconstruction of the images was performed by filtered back-projection (FBP) and using an iterative algorithm (OSEM). SUVs were calculated with and without correction for the blood glucose level using normalisation by body weight, body surface area and lean body mass. Relative percentage changes between SUVs at baseline and follow-up were calculated and analysed for their potential to predict histopathological response to chemotherapy (ROC analysis). Response was defined as less than 10% viable tumour cells in the tumour specimen obtained by surgery 3-4 weeks after the completion of chemotherapy. RESULTS: Eight of 43 patients were histopathological responders to chemotherapy. The percentage changes in SUV(body weight) for responders and non-responders were -52.2 (+/-13.2) and -25.2 (+/-15.2), -54.7 (+/-18.2) and -24.5 (+/-16.1), -53.9 (+/-24.2) and -22.7 (+/-21.3), and -56.7 (+/-21.6) and -26.1 (+/-18.9) for serial scans at 40-min FBP, 40-min OSEM, 90-min FBP and 90-min OSEM, respectively (responders versus non-responders: p<0.01 in each case). According to ROC analysis, neither the scan protocol nor correction for blood glucose significantly influenced the accuracy (approx. 80%) or the cut-off value (approx. -40% change in tumour SUV) for the prediction of response. Normalisation of SUVs by body surface area or lean body mass instead of body weight yielded essentially identical results. CONCLUSION: In gastric carcinomas the prediction of response to chemotherapy on the basis of relative tumour SUV changes is not essentially influenced by any of the methodological variations investigated (time delay after FDG administration, acquisition protocol, reconstruction algorithm, normalisation of SUV). This demonstrates the robustness of FDG PET for therapeutic monitoring and facilitates the comparability of studies obtained at different institutions and with different protocols. However, whichever method is used for therapy monitoring with FDG PET, a highly standardised protocol must be observed to take the dynamics of tumour FDG uptake into account.

Targeting of gelatinase activity with a radiolabeled cyclic HWGF peptide.

Matrix metalloproteinases (MMPs) are a family of proteinases that play an important role in cancer as well as in numerous diseases. In this article, we describe the labeling of a phage display selected cyclic decapeptide containing the HWGF (histidine-tryptophane-glycine-phenylalanine) sequence to target MMP-2 and MMP-9. To evaluate the ability of this labeled peptide to monitor non invasively MMP-2 and MMP-9 activity, in vitro studies, biodistribution, competition studies and plasma metabolites analyses in Lewis Lung cancer tumor bearing mice were performed.

[PET with (18)F-fluorodeoxyglucose for staging of non-small cell lung cancer]. / PET mit (18)F-Fluordeoxyglukose in der Diagnostik des nicht kleinzelligen Bronchialkarzinoms: evidenzbasierte Empfehlungen und Kosten/Nutzenabwägungen.

AIMS: To evaluate studies on the use of positron emission tomography with the glucose analog (18)F-fluoro-deoxyglucose (FDG-PET) for the preoperative staging of patients with non-small cell lung cancer (NSCLC) according to the criteria of evidence based medicine and to discuss the cost-effectiveness of the technique. METHODS: Clinical studies published between 1995 and 2002 on the preoperative staging of non-small cell lung cancer were used for this analysis. Studies that did not meet the criteria published by the European Agency for the Evaluation of Medicinal Products (EMEA) were excluded. The validity of the studies was evaluated by a standardized rating system developed by the Agency for Health Care Policy and Research (AHCPR). RESULTS: For the detection of mediastinal lymph node metastases the mean sensitivity and specificity of FDG-PET on a patient basis is 85% and 87% (16 studies, 1355 patients). In studies that compared FDG-PET and computed tomography (CT) the mean sensitivity of CT was 66% at a specificity of 71%. In the detection of distant metastases FDG-PET correctly changed the tumor stage in 18% of the patients when compared to CT based staging (10 studies, 1073 patients). Five cost effectiveness analyses from the USA, Japan, and Germany concluded that FDG-PET improves the outcome of treatment at reduced or only slightly increased overall costs. Improvement of patient outcome was also demonstrated in a randomized trial, which found that the risk of a futile thoracotomy was reduced by 51% (p=0.003) when FDG-PET was added to the preoperative staging. CONCLUSION: According to the criteria of the AHCPR the use of FDG-PET for detection of mediastinal lymph node and distant metastases is documented at a level of evidence Ia and Ib, respectively. Since systematic analyses also indicate a favorable cost-effectiveness ratio FDG-PET has to be considered as "strictly indicated" for the preoperative staging of non-small cell lung cancer.