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Introduction [177Lu]Lu-DOTATATE is an effective systemic targeted radionuclide therapy for somatostatin receptor (SSTR) positive metastatic or inoperable neuroendocrine tumours (NET). However, for a given injected activity, tumour responses are variable. Our aim was to investigate whether SSTR expression/functionality and known characteristics of intrinsic radiosensitivity, namely proliferation rate, glucose metabolism, cell cycle phase, DNA repair and antioxidant defences were predictors of sensitivity to [177Lu]Lu-DOTATATE in SSTR expressing human cancer cell lines. Methods In six human cancer cell lines and under basal condition, SSTR expression was assessed by qRT-PCR and immunocytochemistry. Its functionality was evaluated by binding/uptake assays with [68Ga]Ga- and [177Lu]Lu-DOTATATE. The radiosensitivity parameters were evaluated as follows: proliferation rate (cell counting), glucose metabolism ([18F]FDG uptake), antioxidant defences (qRT-PCR, colorimetric assay, flow cytometry), DNA repair (qRT-PCR) and cell cycle (flow cytometry). Effect of [177Lu]Lu-DOTATATE on cell viability was assessed 3, 7 and 10 days after 4 h incubation with [177Lu]Lu-DOTATATE using crystal violet. Results Based on cell survival at day 10, cell lines were classified into two groups of sensitivity to [177Lu]Lu-DOTATATE. One group with 20% of survival decrease (−22 to −33%) compared to the untreated control cell lines. The latter had significantly lower total antioxidant capacity, glutathione (GSH) levels and glucose metabolism (p 0.22), combined catalase and GSH peroxidase expression (p = 0.42) and superoxide dismutase (SOD) activity (p = 0.41) were not significantly different between the two groups. Conclusion Antioxidant defences may be major determinants in [177Lu]Lu-DOTATATE radiosensitivity.

BACKGROUND Early prediction of nonresponse is essential in order to avoid inefficient treatments. PURPOSE To evaluate if parametrical response mapping (PRM)-derived biomarkers could predict early morphological response (EMR) and pathological complete response (pCR) 24-72 hours after initiation of chemotherapy treatment and whether concentric analysis of nonresponding PRM regions could better predict response. STUDY TYPE This was a retrospective analysis of prospectively acquired cohort, nonrandomized, monocentric, diagnostic study. POPULATION Sixty patients were initially recruited, with 39 women participating in the final cohort. FIELD STRENGTH/SEQUENCE A 1.5T scanner was used for MRI examinations. ASSESSMENT Dynamic contrast-enhanced (DCE)-MR images were acquired at baseline (timepoint 1, TP1), 24-72 hours after the first chemotherapy (TP2), and after the end of anthracycline treatment (TP3). PRM was performed after fusion of T1 subtraction images from TP1 and TP2 using an affine registration algorithm. Pixels with an increase of more than 10% of their value (PRMdce+) were corresponding nonresponding regions of the tumor. Patients with a decrease of maximum diameter (%dDmax) between TP1 and TP3 of more than 30% were defined as EMR responders. pCR patients achieved a residual cancer burden score of 0. STATISTICAL TESTS T-test, receiver operating characteristic (ROC) curves, and logistic regression were used for the analysis. RESULTS PRM showed a statistical difference between pCR response groups (P < 0.01) and AUC of 0.88 for the prediction of non-pCR. Logistic regression analysis demonstrated that PRMdce+ and Grade II were significant (P < 0.01) for non-pCR prediction (AUC = 0.94). Peripheral tumor region demonstrated higher performance for the prediction of non-pCR (AUC = 0.85) than intermediate and central zones; however, statistical comparison showed no significant difference. DATA CONCLUSION PRM could be predictive of non-pCR 24-72 hours after initiation of chemotherapy treatment. Moreover, the peripheral region showed increased AUC for non-pCR prediction and increased signal intensity during treatment for non-pCR tumors, information that could be used for optimal tissue sampling. LEVEL OF EVIDENCE 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;51:1403-1411.

Background and Objectives: Selection for surgery in patients with colorectal liver metastases (CRLM) remains inaccurate. We evaluated if CRLM baseline metabolic characteristics, assessed by [18]F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT), could predict postoperative outcomes. Methods: In a retrospective series of patients undergoing surgery for CRLM, we defined two groups: the long-term survival (LTS) and early relapse (ER) groups, where the postoperative recurrence-free survivals were ≥5 years or 4.3, defining low- and high-risk mCRS by scores of 0 to 2 and 3 to 6, respectively. Results: From a series of 450 patients operated for CRLM (mean follow-up of 58 months), we included for analysis 23 and 30 patients in the LTS and ER groups, respectively. Clinicopathologic parameters and CRS were similar in the LTS and ER groups. Median SUVmax/SUVmean(liver) ratios were higher in ER vs LTS patients (4.2 and 2.8, P =.008, respectively). mCRS was increased in ER patients (P =.024); 61% of LTS patients had low-risk mCRS and 73% of the ER patients had high-risk mCRS (P =.023). Conclusions: 18FDG-PET/CT characteristics combined with traditional CRS may represent a new tool to improve selection for surgery in patients with CRLM., SCOPUS: ar.j, info:eu-repo/semantics/published

Background and Objectives The histological growth pattern (HGP) represents a strong prognostic factor in patients undergoing surgery for colorectal liver metastases (CRLM). We evaluated whether the combination of HGP with clinico-metabolic parameters could improve its prognostic value. Methods In a series of 108 patients undergoing resection of CRLM, the HGP of CRLM was scored according to international guidelines. Baseline clinico-metabolic clinical status was evaluated using a metabolic-Clinical Risk Score (mCRS), combining traditional Memorial Sloan Kettering-CRS parameters with the tumor-to-liver glucose uptake ratio as measured with (18)Fluorodeoxyglucose/positron emission tomography. Results In patients with desmoplastic HGP (DHGP) CRLM (20% of all patients), 5- and 10-years overall survival (OS) and disease free survival (DFS) were 66% and 43% and 37% and 24.5%, as compared with 35% and 21% and 11% and 11% in the non-DHGP group (p = 0.07 and 0.054). Among DHGP patients, those with a low-risk mCRS had improved postoperative outcomes, 5- and 10-years OS and DFS reaching 83.3% and 62.5% and 50% and 33%, as compared with 18% and 0% and 0% and 0% in high-risk mCRS patients (p = 0.007 and 0.003). In contrast, mCRS did not influence postoperative survivals in non-DHGP patients. Conclusions Combining the clinico-metabolic characteristics with the HGP may improve prognostication in patients undergoing surgery for CRLM.

Objective To assess the impact of a novel molecular imaging technique, 68Ga-(HBED-CC)-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT), in the clinical management of patients with prostate cancer with rising prostate-specific antigen (PSA) after treatment with curative intent. Patients and Methods In all, 131 consecutive patients were referred to our centre for a 68Ga-PSMA PET/CT in the setting of recurring prostate cancer. Of these patients, 11/131(8%) presented with persistent PSA after radical prostatectomy, while 120/131 (92%) were referred for biochemical recurrence after surgery, radiotherapy or both. The images where taken 1 h after injection of 2 MBq/kg of the 68Ga-(HBED-CC)-PSMA ligand. All examinations were interpreted by two experienced nuclear medicine specialists. Using the results of the examination, a multidisciplinary oncology committee (MOC) reported on the treatment strategy. A positive impact on clinical management was considered if the examination determined a modification in the treatment strategy compared to the MOC decision before PSMA imaging. Results All patients completed the examination with no adverse reactions. The median (interquartile range) PSA level at the time of the examination was 2.2 (0.72–6.7) ng/mL. Overall, 68Ga-PSMA PET/CT detected at least one lesion suspicious for prostate cancer in 98/131 (75%) patients. There was an impact on subsequent management in 99/131 patients (76%). The main modifications included continuing surveillance (withholding hormonal therapy), hormonal manipulations, stereotaxic radiotherapy, salvage radiotherapy, salvage node dissection or salvage local treatment (prostatectomy, high-intensity focussed ultrasound). Conclusion Our preliminary experience suggests that performing 68Ga-PSMA PET/CT in patients with prostate cancer with rising PSA after treatment with curative intent can be clinically useful as it changes the treatment strategy in a significant proportion of patients. However, larger prospective trials are needed to validate our present findings.

Molecular imaging of metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer reveals marked intra- and interpatient heterogeneity in HER2 mapping, which correlates with clinical outcome under T-DM1 therapy.Only human epidermal growth factor receptor (HER)2 status determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) has been validated to predict efficacy of HER2-targeting antibody-drug-conjugate trastuzumab emtansine (T-DM1). We propose molecular imaging to explore intra-/interpatient heterogeneity in HER2 mapping of metastatic disease and to identify patients unlikely to benefit from T-DM1.HER2-positive mBC patients with IHC3+ or FISH a parts per thousand yen2.2 scheduled for T-DM1 underwent a pretreatment HER2-positron emission tomography (PET)/computed tomography (CT) with Zr-89-trastuzumab. [F-18]2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT was performed at baseline and before T-DM1 cycle 2. Patients were grouped into four HER2-PET/CT patterns according to the proportion of FDG-avid tumor load showing relevant Zr-89-trastuzumab uptake (> blood pool activity): patterns A and B were considered positive (> 50% or all of the tumor load 'positive'); patterns C and D were considered negative (> 50% or all of the tumor load 'negative'). Early FDG-PET/CT was defined as nonresponding when > 50% of the tumor load showed no significant reduction of FDG uptake (In the 56 patients analyzed, 29% had negative HER2-PET/CT while intrapatient heterogeneity (patterns B and C) was found in 46% of patients. Compared with RECIST1.1, respective NPV/PPV for HER2-PET/CT were 88%/72% and 83%/96% for early FDG-PET/CT. Combining HER2-PET/CT and FDG-PET/CT accurately predicted morphological response (PPV and NPV: 100%) and discriminated patients with a median TTF of only 2.8 months [n = 12, 95% confidence interval (CI) 1.4-7.6] from those with a TTF of 15 months (n = 25, 95% CI 9.7-not calculable).Pretreatment imaging of HER2 targeting, combined with early metabolic response assessment holds great promise for improving the understanding of tumor heterogeneity in mBC and for selecting patients who will/will not benefit from T-DM1.NCT01565200.

Background The purpose of this study was to assess the efficacy and safety of sorafenib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) and to explore the predictive value of early metabolic responses. Methods Sorafenib was administered orally at 400 mg bid on a continuous basis. The primary endpoint was the response rate. Correlation of early 18fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT response to time-to-event outcomes was a secondary objective. Results Twenty-three patients were included in this study. Grade 3 to 4 toxicities included fatigue (22%), hand-foot syndrome (9%), lymphopenia (17%), hyponatremia (39%), and hypophosphatemia (48%). One patient (5%) had a partial response (PR) and 12 patients (55%) had stable disease. Early metabolic response rate was 38%. Median progression-free survival (PFS) was 2.2 months in early metabolic nonresponders (13 of 21 patients) in comparison to 7.4 months in the 8 patients with class I early metabolic response (p = .006). Conclusion Sorafenib showed a modest antitumor activity. Data suggest a possible role of 18FDG PET metabolic response as an early predictor of a prolonged PFS. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

To compare various computed tomography (CT) parameters to the positron emission tomography with computed tomography (PET-CT) response, with or without PET guidance for the response assessment of colorectal cancer (CRC) metastases treated by Y90 radioembolization.Thirty-six CRC metastases were retrospectively evaluated on 18F-Fluoro-Deoxy-Glucose PET-CT and contrast-enhanced computed tomography (CECT) performed at baseline and 2-3 months after Y90 radioembolization.Median SUVmax values decreased from 11.39 to 6.71 after radioembolization (P.001), and 23/36 (64%) metastases were categorized metabolic responses according to European Organisation for Research and Treatment of Cancer criteria. Only a decrease of the mean attenuation in the structural (P.001) and metabolic active volume (P.001) was observed. The change in these criteria was correlated with the change of SUVmax.

Purpose: To compare using immuno-PET/CT the distribution of 89Zr-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with 90Y-labelled rituximab in CD20+ B-cell lymphoma. Methods: Five patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline 89Zr-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m2) of unlabelled rituximab followed by injection of 89Zr-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by 90Y-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed. Results: With a cold rituximab preload, the calculated whole-body dose of 90Y-rituximab was similar (mean 0.87 mSv/MBq, range 0.82–0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59 % and 87 % was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion. Conclusion: Administration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the “prerituximab era”. Clinical Trial Application: CTA 2011-005474-38 Trial Registry: EudraCT, SCOPUS: ar.j, info:eu-repo/semantics/published

INTRODUCTION Leiomyoma is the most common benign tumor of the esophagus (67–80%), it represents 0.4–1% of all esophageal tumors. PRESENTATION OF CASE An incidentally discovered gastro-esophageal submucosal tumor was found to have increased fluorine-18-fluorodeoxyglucose (FDG) uptake on positron emission computed tomography (PET/CT). After laparoscopic surgical exploration and local enucleation the tumor turned out to be a benign esophageal leiomyoma. DISCUSSION There are few reports of esophageal leiomyomas with a positive uptake on (PET/CT) and even fewer adopting our combination of a minimally invasive approach and frozen section examination as a management plan. Our approach avoided excessive morbid surgical resections and underestimation of a malignant disease. CONCLUSION We report this case hoping to expand the existing literature on the topic and to highlight the limitations of PET/CT in guiding the diagnosis and subsequently the management of esophageal submucosal tumors.

OBJECTIVES: The aim of the study was to evaluate prospectively the usefulness of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in investigation of fever of unknown origin (FUO) in HIV-positive patients and to determine whether HIV viraemia impacts on FDG-PET/CT performance. METHODS: The FDG-PET/CT results of 20 HIV-infected patients with FUO were analysed and compared with the FDG-PET/CT results of 10 HIV-infected viraemic patients without FUO. The performance of FDG-PET/CT for identifying the aetiology of FUO was assessed. Final diagnosis for FUO was based on histopathology, microbiological assays, or clinical and imaging follow-up. RESULTS: FDG-PET/CT contributed to the diagnosis or exclusion of a focal aetiology of the febrile state in 80% of patients with FUO. The presence of increased FDG uptake in the central lymph node has 100% specificity for focal aetiology of fever, even in viraemic patients. The absence of hypermetabolic central lymph nodes in FUO patients has 100% negative predictive value for focal disease. Lymph node biopsy in central hypermetabolic areas allowed, in 100% of cases, identification of underlying disease in patients with FUO. Biopsy of peripheral lymph nodes should be performed in lymph nodes with maximum standardized uptake value (SUVmax) ≥ 6-8 (sensitivity 62.5%; specificity 75%) and avoided in lymph nodes with SUVmax = 0-4 (specificity 0%). High HIV viraemia does not prevent correct interpretation of FDG-PET/CT. CONCLUSIONS: As in HIV-negative patients, we confirm the usefulness of FDG-PET/CT in investigation of FUO in HIV-positive patients even if they are viraemic.

Intraarterial administration of (90)Y microspheres to the spleen in patients with malignant lymphoma was mentioned once in the literature in 1973. This case study illustrates the potential indication of selective internal radiotherapy in a heavily pretreated patient with highly refractory disease with a marginal zone lymphoma in leukemic phase and symptomatic splenomegaly. We describe the clinical course of disease; the biological and clinical response to the treatment after radioembolization; and simulation and dosimetry by multimodal imaging via single-photon emission computed tomography and computed tomography. The advantages of radioembolization for the management of lymphomatous splenomegaly are discussed.

Resume Introduction Peu de donnees sont disponibles concernant la valeur predictive de la TEP-TDM dans l’evaluation de la reponse a la chimiotherapie des CBNPC a un stade avance et son impact sur la survie ulterieure. Methodes Etude retrospective de patients atteints de CBNPC ayant eu une TEP-TDM avant et apres trois premieres cures de chimiotherapie. Les evaluations morphologique et metabolique ont ete realisees respectivement selon les criteres RECIST/OMS et EORTC. La relation entre reponse et survie ulterieure a ete evaluee via un modele de regression de Cox. Resultats Inclusion de 59 patients (stades III A /III B /IV : 9/11/39). La survie mediane estimee etait de 40 semaines (44 deces). Aucune difference significative de survie n’a ete observee entre les patients en reponse objective et ceux en maladie stable, que ce soit par l’evaluation morphologique, metabolique ou combinee. Seulement en cas de maladie progressive, la survie est significativement plus courte. La valeur predictive negative de la reponse metabolique pour la reponse morphologique est de 0,90, celle de la progression metabolique pour la progression morphologique est de 0,98. Conclusion Seules les maladies progressives se distinguent significativement des autres categories de reponses avec une detection plus sensible et plus precoce par la TEP-TDM.

PET coupled with computed tomography (CT) is indicated for the management of patients undergoing selective internal radiation therapy (SIRT), both as an aid to treatment planning as well as for post-SIRT dosimetry and the assessment of the metabolic response. PET-CT plays an important role in not only identifying the target tumor volume, but also for the prognostic stratification of patients and the exclusion of those with significant metabolic activity in extrahepatic lesions that cannot be controlled with radiotherapy and/or systemic chemotherapy.

Functional imaging including single photon emission computed tomography, PET and MRI techniques in head and neck squamous cell cancer allows disease characterization beyond structure and morphology.In patients without clinical signs of lymph node involvement, sensitivity of fluoro-2-deoxy-D-glucose PET is only 50%. This has led to the use of sentinel lymph node scintigraphy that seems to be a valid alternative to elective stage dissection. Additionally, the use of single-photon emission computed tomography-computed tomography imaging enables a more accurate localization of the sentinel lymph node scintigraphy. The fluoro-2-deoxy-D-glucose uptake intensity of the head and neck squamous cell carcinoma sites is related to locoregional control and overall survival. In case of suspicion for residual or recurrent head and neck squamous cell carcinoma after surgery or (chemo)radiotherapy, fluoro-2-deoxy-D-glucose-PET has a high sensitivity and seems to be cost-effective in selecting patients for direct laryngoscopy. Diffusion-weighted MRI in combination with size and morphological criteria is a strong predictor of presence of malignant lymph nodes. Initial reports indicate the use of diffusion-weighted imaging for response assessment as early as 1 week after beginning of radiochemotherapy. Perfusion MRI is studied for the measurement of drug effects on tumour (micro)vascularity and capillary permeability.Functional imaging improves the initial staging and the detection of residual or recurrent disease following therapy.

Selective internal radiotherapy (SIRT) using Yttrium-90 labeled resin microspheres is increasingly used for the radioembolization of unresectable liver metastases of colorectal cancer (CRC). The treatment can be simulated by scintigraphy with Tc(99m)-labeled macroaggregates of albumin (MAA). The aim of the study was to develop a predictive dosimetric model for SIRT and to validate it by correlating results with the metabolic treatment response. The simulation of the dosimetry was performed by mathematically converting all liver voxel MAA-SPECT uptake values to the absolute Y(90) activity. The voxel values were then converted to a simulated absorbed dose (Gy) using simple MIRD formalism. The metabolic response was defined as the change in total lesion glycolysis (TLG) on FDG-PET. A total of 39 metastatic liver lesions were studied in eight evaluable patients. The mean administered Y(90) activity was 1.69 GBq (range: 1.33-2.04 GBq). The median (95% CI) simulated absorbed dose (Gy) was 29 Gy (1–98 Gy) and 66 Gy(32–159 Gy) in the poor (50% TLG change) and the good responders (TLG change50%),respectively [DOSAGE ERROR CORRECTED].Using a simple cut-off value of 1 for the MAA-tumor-to-normal uptake ratio, a significant metabolic response was predicted with a sensitivity of 89% (17/19), a specificity of 65% (13/20), a positive predictive value of 71% (17/24) and a negative predictive value of 87% (13/15). Integrated multimodality imaging allows prediction of metabolic response post radioembolization using Y(90)-resin microspheres, and should be used for patient selection.

The utility of positron emission tomography-computed tomography has increasingly been studied during the last years. Positron emission tomography-computed tomography offers a holistic approach of cancer diagnosis as it can integrate structural, functional, metabolic, and molecular information of tumour. The technique offers three-dimensional, high-resolution, whole body, and quantitative imaging. 18F-Fluoro-2-deoxy-D-glucose still remains the only tracer widely available. Other tracers have been designed for assessment of proliferation, amino acid uptake, and hypoxia.18F-Fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography seems the most appropriate technique for the assessment of locoregional lymph node involvement in head and neck cancer. False negativity of positron emission tomography-computed tomography in case of micrometastatic lymph node disease should be compensated by the implementation of the sentinel node scintigraphy guided biopsy. 18F-Fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography has a very high sensitivity and negative predictive value in detecting residual disease after radiotherapy or early recurrent disease. Radiotherapy planning can use the 18F-fluoro-2-deoxy-D-glucose uptake distribution for increasing the accuracy of delineation of the target volumes in conformal radiotherapy. Positron emission tomography-computed tomography with other tracers such as deoxy-18F-fluorothymidine for proliferation mapping and [F-18] fluoromisonidazole for hypoxia mapping are currently being studied.Major studies have now confirmed the utility of positron emission tomography-computed tomography in the different phases of diagnostic and therapeutic phases of the management of patients with head and neck cancer.

Purpose: To investigate and compare the quantitative accuracy of 90Y imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres. Methods: A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of 90Y solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. Results: Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current generation scanners from GE, Philips and Siemens could reconstruct background concentration measures to within 10 % of true values over the evaluated range, with greater deviations on the Philips systems at low count rates, and demonstrated typical partial volume effects on hot sphere recovery, which dominated spheres of diameter 20 mm in diameter, activity concentrations were consistently underestimated by about 20 %. Non-ToF scanners from GE Healthcare and Siemens were capable of producing accurate measures, but with inferior quantitative recovery compared with ToF systems. Conclusion: Current generation ToF scanners can consistently reconstruct 90Y activity concentrations, but they underestimate activity concentrations in small structures (≤37 mm diameter) within a warm background due to partial volume effects and constraints of the reconstruction algorithm. At the highest count rates investigated, measures of background concentration (about 300 kBq/ml) could be estimated on average to within 1 %, 5 % and 2 % for GE Healthcare (all-pass filter, RR + ToF), Philips (4i8s ToF) and Siemens (2i21s all-pass filter, RR + ToF) ToF systems, respectively. Over the range of activities investigated, comparable performance between GE Healthcare and Siemens ToF systems suggests suitability for quantitative analysis in a scenario analogous to that of postradioembolization imaging for treatment of liver cancer., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein that is a well-characterized and clinically validated marker of prostate cancer (PCa) Gallium 68 (68Ga)–labeled PSMA PET/CT uses the affinity of the 68Ga-labeled PSMA ligand to PSMA expressing cells. Promising results were reported for an accurate staging in patients presenting with biochemical recurrence (BCR) after primary treatment even at low PSA levels. We present the case of a 56 years old patient presenting with a BCR (PSA=21 ng/ml) several years after external radiation beam therapy. Abdominopelvic CT scan and bone scan were negative. A suspicious lesion on PSMA-ligand PET imaging was detected in the prostate with no evidence of regional or distant hypermetabolic lesions

Background Lhermitte-Duclos disease is a cerebellar lesion, characterized by an overgrowth of cerebellar ganglion cells, which replace granular cells and Purkinje cells. Lhermitte-Duclos disease may be a manifestation of Cowden syndrome (multiple hamartoma-neoplasia syndrome). The nature of LDD, whether neoplastic, dysplastic, or hamartomatous, is still not exactly understood. Metabolic imaging of the amino acid metabolism using PET could be useful for noninvasive characterization of these lesions. Methods To define the Meth-PET imaging characteristics of these lesions, we undertook a Meth-PET study in 4 patients with LDD after obtaining informed consent. All 4 patients had clinical signs of Cowden syndrome. In 2, the diagnosis was made with MRI; in 2, it was confirmed histologically. Results Using Meth-PET, the cerebellar lesions had a high methionine uptake, except in the subtotally resected lesion. The uptake of the lesions was markedly higher than that of the contralateral normal regions. The mean L/C ratio was 2.07. Conclusion 11C-methionine positron emission tomography visualizes the lesion of Lhermitte-Duclos disease as a high uptake area. This amino acid hypermetabolism may be related to the slow growth of the lesions, and is an argument to suggest that patients with LDD should be followed up carefully to detect progression of the cerebellar lesion.

The presence of lymph node involvement (N) and distant metastasis (M) in patients with invasive bladder carcinoma is a major determinant of survival and, therefore, a pivotal element in the therapeutic management. The aim of this prospective study was to evaluate the use of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in this indication. Whole-body FDG-PET and computed tomography (CT) were performed in 55 patients with non-metastatic invasive bladder cancer for preoperative staging. Correlative imaging of PET with CT was performed, leading to a PET(CT) result. The imaging results were compared with the gold standard, consisting of histopathology (lymphadenectomy, guided biopsy) or clinical follow-up for 12 months, and related to overall survival using the Kaplan-Meier method. The gold standard was available in 40 patients and indicated NM-positive disease in 15 patients (12 N lesions, 8 M lesions), and NM-negative disease in 25 patients. For the diagnosis of NM-positive disease, the sensitivity, specificity and accuracy of PET(CT) were 60%, 88% and 78%, respectively. Diagnostic discordances between PET(CT) and CT alone were found in 9/40 patients, among whom PET was correct in six (15%): three with true-positive and one with true-negative distant metastases, and two with true-negative lymph nodes. Median survival time of patients in whom PET(CT) indicated NM-positive disease was 13.5 months, compared with 32.0 months in the patients with a NM-negative PET(CT) (p=0.003). Addition of metabolism-based information provided by FDG-PET to CT in the preoperative staging of invasive bladder carcinoma yields a high diagnostic and prognostic accuracy.

Purpose of review Positron emission tomography using the positron emitting glucose analogue 18F-fluorodeoxyglucose has recently emerged as a promising metabolism-based whole-body imaging tool for cancer diagnosis and follow-up. Several reports have recently appeared indicating the potential and limitations of this technique. The review limits its scope to the recent advances of 18F-fluorodeoxyglucose positron emission tomography in the clinical management of gastric and esophageal cancer. Recent findings New studies have been reported on the use of 18F-fluorodeoxyglucose positron emission tomography to assess the early and late metabolic response of a gastroesophageal tumor to chemo(radiation) therapy. The metabolic response as measured by serial 18F-fluorodeoxyglucose positron emission tomography, performed before and during treatment or some weeks thereafter, can be used to predict the clinical and histopathologic response. Moreover, the metabolic positron emission tomography response seems to be related to overall and disease-free survival. Summary Gastroesophageal 18F-fluorodeoxyglucose positron emission tomography could add significant diagnostic information to the different phases of patient management. At initial diagnosis of esophageal cancer, positron emission tomography detects more distant lymph node and organ metastases compared with conventional diagnostics, allowing a more accurate selection of the most appropriate treatment. Serial 18F-fluorodeoxyglucose positron emission tomography performed before and during chemotherapy allows early identification of nonresponding tumors. 18F-fluorodeoxyglucose positron emission tomography performed after a treatment allows accurate assessment of the residual tumor load. 18F-fluorodeoxyglucose positron emission tomography allows accurate detection and restaging of recurrent disease.

� Treatment of malignant glioma is difficult and discouraging. Even after resection and maximal adjuvant therapy, the prognosis remains poor. The authors sought a novel form of treatment, such as stimulating the patient’s own immune response against the tumor, and developed a protocol of tumor vaccination in which autologous dendritic cells (DCs) were used in patients with recurrent malignant glioma. A 4-year-old girl was treated by means of biopsy sampling and radiotherapy for a rolandic low-grade glioma. Ten years later, a Grade III recurrence was discovered and treated with subtotal resection, interstitial radiation, six courses of oral temozolomide, and 12 courses of oral VP16. At the end of the chemotherapy cycle, a new rapidly growing recurrence was diagnosed. A macroscopically complete resection was performed. Afterward, the girl was vaccinated with autologous DCs that had been pulsed ex vivo with the homogenate of the resection specimen. She received six vaccines in total. The efficacy of immunization was checked by a positive delayed-type hypersensitivity skin reaction after the second injection. After the fifth vaccine, a transient contrast enhancement without mass effect was visualized on magnetic resonance imaging. Simultaneously, positron emission tomography imaging revealed a transient increase of metabolic activity around the resection cavity, but the metabolic uptake ratio remained below 1.8. The patient’s disease is still in complete remission 24 months after the last surgery. She is clinically well with minor and stable left hemiparesis. This case report illustrates the potential of vaccination with DCs loaded with crude tumor homogenate as adjuvant therapy to induce prolonged tumor control of malignant glioma and the objective noninvasively monitored immune response against infiltrating tumor cells.

Oesophageal clearance of acid and bile: a combined radionuclide, pH, and Bilitec study.Koek GH, Vos R, Flamen P, Sifrim D, Lammert F, Vanbilloen B, Janssens J, Tack J.Centre for Gastroenterological Research, University Hospital Gasthuisberg, KU Leuven, Belgium.BACKGROUND: Studies combining pH and Bilitec monitoring found a high prevalence of both acid and duodeno-gastro-oesophageal reflux in severe reflux disease. Clearance of refluxed material is a major defence mechanism against reflux. Several studies have been devoted to oesophageal acid clearance but oesophageal clearance of refluxed duodenal contents (DC) has rarely been addressed. Aim: To compare oesophageal acid and DC clearance. METHODS: Ten healthy volunteers (five women, mean age 23 (1) years) were studied. Firstly, a balloon tip catheter, positioned in the duodenum under fluoroscopy, was used to aspirate DC after stimulation by a high caloric liquid meal (200 ml, 300 kcal). During the second session, pH and Bilitec probes were positioned 5 cm above the lower oesophageal sphincter and a small infusion catheter was introduced into the proximal oesophagus. The subject was placed supine under a gamma camera. One of two different solutions (DC mixed with 0.2 mCi Tc99m pertechnetate or citric acid (pH 2) mixed with 0.2 mCi Tc99m pertechnetate) was infused into the proximal oesophagus and the subject was instructed to swallow at 20 second intervals. Clearance was assessed using scintigraphy (dynamic acquisition, one frame per second in the anterior view; calculation of time to clear peak counts to background level), pH (time to pH0.14) monitoring, with or without continuous saliva aspiration. Each condition was studied twice in a randomised design; measurement time was four minutes, interrupted by water flushing, with a two minute rest period. Results are given as mean (SEM) and were compared by Student's t test and Pearson correlation. RESULTS: Scintigraphic evaluation showed a volume clearance time of 29 (3) seconds for acid and 28 (9) seconds for DC (NS). Saliva aspiration had no significant influence on volume clearance of acid or DC (28 (4) and 30 (13) seconds, respectively; NS). pH monitoring showed an acid clearance time of 217 (15) seconds, which was significantly prolonged to 324 (30) seconds during saliva aspiration (p

Positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) is increasingly used in the diagnostic management of colorectal cancer patients. It provides a highly sensitive and specific diagnosis which is entirely based upon alterations of the glucose metabolism found in malignant tissues. The information provided by FDG-PET is independent of the underlying structural characteristics of the lesions and, therefore, it is essentially complementary to the available structural imaging modalities such as CT, MRI and (endoscopic) ultrasound. Several studies have now been performed on the use of FDG-PET in colorectal adenocarcinoma for primary pre-operative staging, for diagnosis and (re)staging of recurrent disease, for localization and staging of occult recurrent disease, and for the assessment of the metabolic effects of chemotherapy and radiotherapy. This chapter aims to clarify some fundamental issues of both detection device and radiotracer, the proven indications for FDG-PET, the strength and limitations of the technique, and how its implementation would affect patient management.

The aim of the study was to evaluate the use of positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) in patients with unexplained rising carcinoembryonic antigen (CEA) in the postoperative surveillance of colorectal cancer. 50 consecutive patients with elevated CEA levels and a completely normal (n=31) or equivocal (n=19) conventional diagnostic work-up (CDW) were retrospectively selected. All PET images were reviewed with full knowledge of the CDW. The gold standard consisted of histology, or clinical follow-up of more than 1 year. Recurrent disease was established in 56 lesions in 43 patients. On a patient-based analysis, the sensitivity of FDG-PET was 34/43 (79%), and the positive predictive value 34/38 (89%). In 14/50 patients (28%), the FDG-PET findings led to a surgical resection with curative intent. On a lesion-based analysis, FDG-PET detected 42/56 lesions (sensitivity: 75%), the positive predictive value was 79% (42/53). These results demonstrate that FDG-PET can have a clear impact on patient management in patients with an unexplained elevation in CEA levels.

Salivary gland scintigraphy (SGS) is used to depict salivary gland dysfunction after radiotherapy (RT). The aim of this study was to investigate the utility of SGS combined with single photon emission computed tomography (SPECT). Twenty-one patients with a carcinoma of head and neck underwent SGS before and 1 month after RT. After injection of 370 MBq 99Tcm-pertechnetate, a biplanar dynamic acquisition (12 x 1 min) was started, followed by a SPECT acquisition during 4 min. Carbachol was then injected and a second dynamic study (16 x 1 min) was performed, again followed by a SPECT acquisition. The salivary excretion fraction (SEF) was calculated both from the geometric mean planar image for each parotid and from the SPECT data for each transverse plane through the parotids. The RT-induced changes in the SEF (dSEF) were correlated with the mean radiation dose calculated using tomography-based dosimetry. The mean radiation dose to the parotids was 44 Gy (range 4.4-68.1 Gy). The mean range of the variation in radiation dose to the transverse slices within the parotids of a patient was 24 Gy (range 6.2-51.9 Gy). Considering all transverse planes through the parotids in all patients, a linear correlation was found between the dSEF calculated using SGS-SPECT and the radiation dose (r=0.45, P=0.0001). Thirteen patients had a variation in radiation dose within the parotids of more than 20 Gy. In nine of these a significant intra-individual correlation between radiation dose and the dSEF of the transverse parotid slices was found (r range 0.55-0.97; P value range 0.037-0.0001). In conclusion, SGS-SPECT can be used for monitoring radiation-induced parotid gland dysfunction. It offers the unique possibility for the assessment of intra-individual dose-dysfunction curves in patients with large variations in the radiation dose within the parotids.

OBJECTIVESThe aim of this study was to investigate the prognostic value of carbon-11–acetate (acetate) positron emission tomography (PET) after successful reperfusion of myocardial infarction (MI).BACKGROUNDAcetate PET allows the measurement of both myocardial flow and oxidative metabolism. The prognostic value of acetate measurements performed early (within 24 h) after Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 reperfused MI is unknown.METHODSIn 18 patients with TIMI flow grade 3 reperfusion of their first MI, a dynamic acetate study was performed within 24 h of the acute event. At five days, nitrogen-13–NH3(NH3) and fluorine-18–labeled fluorodeoxyglucose (FDG) PET studies were performed. Infarct-related areas were classified as “PET viable” or “PET nonviable,” as assessed with NH3and FDG, according to previously established criteria. At five days and three months, radionuclide angiography was performed for evaluation of left ventricular (LV) function.RESULTSIn infarct-related regions, myocardial blood flow, FDG uptake and oxygen consumption were decreased, compared with remote regions. However, oxygen consumption values, as measured with acetate in both PET-viable and PET-nonviable areas, as assessed with NH3and FDG, were not significantly different (p = NS). A significant linear correlation was observed between global LV ejection fraction at three months and oxidative metabolism in the infarct-related area (r = 0.8, p < 0.0001). Multivariate analysis revealed that oxidative metabolism measurements in reperfused myocardium was the only significant predictor for recovery of LV function at three months (p < 0.05).CONCLUSIONSMeasurement of oxidative metabolism early after TIMI flow grade 3 reperfusion of MI offers important prognostic value concerning LV function at follow-up.

5-HT2A receptors have been implicated in the pathophysiology of mood disorders and in the therapeutic effect of the so-called atypical antipsychotics. Recently, a new radioiodinated ligand with high affinity and selectivity for serotonin 5-HT2A receptors, 123iodinated 4-amino-N-1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl] 5-iodo-2-methoxybenzamide (123I-5-I-R91150), has been developed and has been shown to be suitable for single-photon emission tomography (SPET) imaging. In this study the influence of age and gender on the ligand binding was investigated in normal volunteers. One hundred and fifty MBq of 123I-5-I-R91150 was administered to 26 normal volunteers (13 females and 13 males) with an age range of 23-60 years. SPET imaging was performed with a triple-headed gamma camera. For semi-quantitative analysis, ratios of ligand binding in different regions of interest to the binding in the cerebellum were calculated. Mean ratios of 1.7 were obtained. No gender difference was demonstrated. 5-HT2A binding was shown to decline with age. Over an age range of 40 years a reduction in ligand binding of 42% +/- 7% was found. These results are in agreement w in vitro and positron emission tomography findings of a decline in 5-HT2A receptor binding with age. The findings confirm the suitability of 123I-5-I-R91150 for SPET imaging of 5-HT2A receptors, and highlight the necessity for age-matched controls in clinical studies.

The uptake of iodine-123 alpha-methyl-l-tyrosine (IMT) in the primary tumours and metastatic lymph nodes of squamous cell carcinoma of the head and neck was examined with single-photon emission tomography (SPET). Eleven patients with biopsy-proven carcinomas were studied prior to any therapeutic action. The evaluation of cervical lymph node involvement was based on the findings of physical examination, computed tomography and magnetic resonance imaging, and in six patients on the histological data relating to tissue samples obtained by fine-needle lymph node aspiration or surgical intervention. SPET imaging was performed 10 min after the injection of 130-170 MBq IMT using a triple-head gamma camera equipped with medium-energy collimators. High-quality IMT SPET depicted the primary tumour in 10 of 11 patients (sensitivity: 91%). Tumours located in the larynx were visualized more clearly than those located in the mouth or oropharynx. The mean tumour-to-background ratio was 2.35 (range: 1.6-3.1) for laryngeal tumours and 1.67 (range: 1.2-2.2) for mouth and oropharyngeal tumours. Metastatic cervical lymph nodes were involved to various degrees in 8 of the 11 patients. Among these eight patients there were 16 sites, nine of which were detected by IMT SPET (sensitivity: 56%). If the IMT SPET findings were recorded per side of the neck, the sensitivity was 64%. Five of the seven missed metastatic lymph nodes were smaller than 15 mm. The mean tumour-to-background ratio of the scintigraphically visualized lymph nodes was 1.81+/-0.51 (range: 1.39-2.77). Asymmetric physiological submandibular salivary gland IMT uptake led to false-positive lymph node assessment in three patients. This study indicates the potential use of IMT SPET as a metabolic imaging modality in patients with head and neck squamous cell carcinoma.

Dermatofibrosarcoma protuberans is a soft-tissue tumor that may recur locally and rarely causes metastases to vital organs. Dermatofibrosarcoma protuberans has specific chromosomal abnormalities involving the platelet-derived growth factor beta-chain locus that may render these tumors responsive to targeted therapy with the tyrosine kinase inhibitor imatinib mesylate. A patient with locally recurrent and metastatic dermatofibrosarcoma protuberans who had already undergone surgery 22 times was initially treated with imatinib mesylate 400 mg/day. The treatment dose was increased after 7 days to 400 mg twice daily. The patient was followed up for response and toxicity by physical examination and imaging studies, comprising computed tomography and fluorodeoxyglucose positron emission tomography. Clinical response could be demonstrated after the first month of treatment, and subsequent computed tomography and positron emission tomography documented a response to imatinib mesylate therapy. Our patient is now in sustained remission with minimal toxicity. We conclude that antitumor activity of metastatic dermatofibrosarcoma protuberans can be obtained with imatinib mesylate treatment with minimal side-effects.

Purpose: To compare the performance of eight metabolic indices for the early assessment of tumour response in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. Methods: Forty patients with advanced mCRC underwent two FDG PET/CT scans, at baseline and on day 14 after chemotherapy initiation. For each lesion, eight metabolic indices were calculated: four standardized uptake values (SUV) without correction for the partial volume effect (PVE), two SUV with correction for PVE, a metabolic volume (MV) and a total lesion glycolysis (TLG). The relative change in each index between the two scans was calculated for each lesion. Lesions were also classified as responding and nonresponding lesions using the Response Evaluation Criteria In Solid Tumours (RECIST) 1.0 measured by contrast-enhanced CT at baseline and 6-8 weeks after starting therapy. Bland-Altman analyses were performed to compare the various indices. Based on the RECIST classification, ROC analyses were used to determine how accurately the indices predicted lesion response to therapy later seen with RECIST. Results: RECIST showed 27 responding and 74 nonresponding lesions. Bland-Altman analyses showed that the four SUV indices uncorrected for PVE could not be used interchangeably, nor could the two SUV corrected for PVE. The areas under the ROC curves (AUC) were not significantly different between the SUV indices not corrected for PVE. The mean SUV change in a lesion better predicted lesion response without than with PVE correction. The AUC was significantly higher for SUV uncorrected for PVE than for the MV, but change in MV provided some information regarding the lesion response to therapy (AUC >0.5). Conclusion: In these mCRC patients, all SUV uncorrected for PVE accurately predicted the tumour response on day 14 after starting therapy as assessed 4 to 6 weeks later (i.e. 6 to 8 weeks after therapy initiation) using the RECIST criteria. Neither correcting SUV for PVE nor measuring TLG improved the assessment of tumour response compared to SUV uncorrected for PVE. The change in MV was the least accurate index for predicting tumour response. © 2012 The Author(s)., SCOPUS: ar.j, info:eu-repo/semantics/published

Purpose of the study: Fever of unknown origin (FUO) is a challenging clinical entity in HIV patients. FDG-PET/CT is well validated in the work-up of FUO in HIV-negative patients but in HIV viremic patients, metabolism of HIV reactive lymph nodes could decrease its specificity. We prospectively evaluated the usefulness of FDG-PET/CT in FUO in HIV-positive patients and in particular whether HIV viremia impacts on FDG-PET/CT performance. Methods: FDG-PET/CT was performed in 20 HIV patients with FUO and compared with FDG-PET/CT in 10 HIV viremic patients without FUO. Final diagnosis for FUO was based on histopathology, microbiology, or clinical and imaging follow-up. Mode of diagnosis, accordance of FDG-PET/CT with final diagnosis, localization of invasive diagnosis procedures was recorded in order to assess usefulness of FDG-PET/CT. Results : FDG-PET/CT showed a different pattern in FUO and asymptomatic viremic patients. Reactive HIV lymph nodes in asymptomatic viremic patients were mostly peripheral with mean SUVmax of 6.5. In patients with FUO and underlying focal pathologies, hypermetabolic lymph nodes were central with mean SUVmax of 11.6. Presence of central lymph nodes with high FDG uptake in had a 100% specificity for focal pathology, even in viremic patients and absence of these had 100% negative predictive value. Lymph node biopsy in central hypermetabolic areas allowed identifying underlying disease in all FUO patients. For peripheral lymph nodes, a ROC curve was built in order to define the best cut-off of SUVmax for biopsy: SUVmax of 6-8 showed a sensitivity of 62.5% and specificity of 75%. Lymph nodes with SUVmax

Purpose of review (18)F-fluoro-2-deoxy-D-glucose PET-computed tomography (CT) has a major clinical impact in oncology not only for diagnostics but also for staging, response assessment, and relapse detection. However, several other PET tracers are needed for a more complete molecular characterization of cancers which has great importance in the era of individualized targeted therapies. PET-CT is an exquisite tool for molecular imaging because it allows detection of nanomolar quantities of tracer molecules targeting different hallmarks of cancer. Recent findings This article reviews the most recent findings (published in 2010-2011) on the use of molecular imaging for assessing tumour proliferation, apoptosis, growth receptor expression, bone metabolism, and hypoxia. Summary Molecular imaging using PET-CT constitutes a major opportunity in translational research bringing fundamental molecular insights to the clinical area. Such information results invaluable for patient selection and prediction of response to therapy and serves as a crucial diagnostic tool in the era of personalized medicine.

Medical oncology needs early identification of patients that are not responding to systemic therapy. (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) performed before and early during treatment has been proposed for this purpose. However, the best way to assess the change in FDG uptake between two scans has not been identified. We studied cutoff thresholds to identify responding tumours as a function of the method used to measure tumour uptake., Evaluation Studies, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Adequate patient selection and treatment planning is crucial for a safe and cost-effective administration of selective internal radiotherapy (SIRT) of malignant liver disease using 90Y-labelled microspheres. It requires the implementation of multimodality imaging, integrating metabolic, functional and structural characteristics. A multidisciplinary approach is a prerequisite for SIRT, bringing together the knowhow and expertise of radiologists, nuclear medicine physicians, medical physicists, imaging engineers, and radiotherapists. This review discusses the available radiologic (CT/MRI) and nuclear (SPECT/PET) imaging modalities and their specific utility in the different diagnostic phases related to SIRT: whole body and intrahepatic pre-treatment disease staging, CT and MRI-based angiography, liver-lung shunt assessment, treatment simulation, predictive dosimetry, post-treatment imaging, and SIRT response assessment.

A 51-year-old man presented with generalised bone pain. Initial evaluation revealed a low serum phosphorus level and elevated urinary phosphorus excretion. Aminoaciduria was normal. Standard imaging showed only minimal changes. The patient was treated with daily oral supplementation with phosphate (1 g/day) and 1,25-dihydroxy vitamin D3 (1 μg/day) to maintain euphosphataemia. In spite of the fact that this treatment was maintained for 3 years, there was no modification of renal phosphate clearance. A diagnosis of hypophosphataemic osteomalacia with renal phosphate wasting was proposed. Therefore, tumour-induced osteomalacia was suspected, triggering a diagnostic workup to find the primary tumour. These tumours are known to express somatostatin receptors, so whole body positron emission tomography (CT) imaging was performed after intravenous administration of 68Ga-DOTA-TOC ( 68Ga-DOTA-D-Phe1-Tyr3-pentreotide). A solitary intense hot spot was detected in soft tissue near the right femoral internal condyle. Based on this result, curative resection of the tumour was performed., SCOPUS: ar.j, info:eu-repo/semantics/published

Evidence is accumulating that radiotherapy of non-small cell lung cancer patients can be optimized by escalating the tumour dose until the normal tissue tolerances are met. To further improve the therapeutic ratio between tumour control probability and the risk of normal tissue complications, we firstly need to exploit inter patient variation. This variation arises, e.g. from differences in tumour shape and size, lung function and genetic factors. Secondly improvement is achieved by taking into account intra-tumour and intra-organ heterogeneity derived from molecular and functional imaging. Additional radiation dose must be delivered to those parts of the tumour that need it the most, e.g. because of increased radio-resistance or reduced therapeutic drug uptake, and away from regions inside the lung that are most prone to complication. As the delivery of these treatments plans is very sensitive for geometrical uncertainties, probabilistic treatment planning is needed to generate robust treatment plans. The administration of these complicated dose distributions requires a quality assurance procedure that can evaluate the treatment delivery and, if necessary, adapt the treatment plan during radiotherapy.

Positron emission tomography using F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is increasingly used in breast cancer. The new generation cameras integrate PET and CT within the same camera, allowing the simultaneous assessment of the structural and metabolic aspects of disease. There is presently a controversy on the clinical significance of osteoblastic bone metastases in breast cancer which are not detected on FDG-PET. It has been suggested that these radiologically dense lesions represent the result of successful treatment of initially osteolytic lesions. We report a case of a 65-year-old woman with a suspicion of recurrent breast cancer based on an increasing serum tumor marker. Serial PET/CT showed progressive blastic bone metastases on the CT without FDG uptake. These lesions were confirmed by bone single photon emission computed tomography. This case report shows: first, that progressive osteoblastic lesions can lack FDG-avidity, leading to a false-negative PET; and secondly, that bone scintigraphy should not be replaced by FDG-PET/CT for the detection of bone metastases in breast cancer.

Thyroid carcinomas are fairly uncommon and include a broad range of disease types: 94% are differentiated thyroid carcinoma (DTC), 5% are medullary thyroid carcinoma (MTC), and the remaining 1% are anaplastic thyroid carcinoma (ATC). DTCs are derived from the follicular epithelial cells and are either papillary thyroid carcinoma or follicular thyroid carcinoma. MTC is a calcitonin and carcinoembryonic antigen (CEA) secreting neuroendocrine tumor of the parafollicular C-cells of the thyroid. ATC is a very aggressive tumor with poor prognosis characterized by extended local invasion and high frequency of distant metastases at the time of initial diagnosis. Positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (FDG) as the radiotracer depicts cancer sites based on their increased glucose metabolism. The normal thyroid shows low avidity for FDG. The enhanced ability of thyroid cancers to transport and accumulate glucose is the basis for the use of FDG-PET to identify malignant tumors and metastases. More precisely, the increased FDG accumulation is based on an increased expression of glucose transporters (GLUT), together with an increase of hexokinase activity and a decreased activity of phosphatase seen in most types of tumors. The technique is increasingly used in cancer care because the molecular and metabolic mechanisms underlying the FDG uptake are completely independent of associated structural characteristics, resulting in a superior diagnostic specificity, and because metabolic changes precede structural changes, increasing its sensitivity for early disease stages and its potential for early assessment of the post-therapeutic effects. © 2008 Elsevier Inc.

Merkel cell carcinoma (MCC) is a rare and highly malignant skin cancer with neuroendocrine differentiation. We studied the potential value of 18FDG PET in the management of MCC. Eleven patients with MCC were examined by 18FDG PET and PET-CT for staging purpose (n=4) or for detection of recurrence (n=7). Qualitative and quantitative interpretation of PET studies was performed routinely. 18FDG PET observations were compared to clinical and radiological findings. In 6 patients, PET findings were also compared to histology. In 7 patients, the 18FDG tumor uptake was compared to the MCC proliferative activity expressed by the Ki-67 index. 18FDG PET was contributive in 10/11 MCC patients. In 7 patients, 18FDG PET detected focal lesions or a disseminated stage of the disease including dermal, nodal and visceral metastases. In 3 patients, a normal 18FDG PET confirmed complete remission of disease. Most MCC patients exhibited highly 18FDG-avid sites suggestive of increased glucose metabolism. This imaging pattern was related to a high proliferative activity (Ki-67 index >50%). In 1 patient with a weakly proliferative nodal MCC (Ki-67

Positron emission tomography (PET) is the most sensitive and specific technique for in vivo imaging of metabolic pathways and receptor–ligand interactions in the tissues of man (Jones 1996). PET uses positron emitting short living radioisotopes of natural elements, such as oxygen-15, carbon-11, nitrogen-13, and fluorine-18. These radioisotopes allow the synthesis of numerous positron-emitting radiopharmaceuticals targeting specific functional or metabolic expressions (phenotypes) of the disease. Depending on the selected radiopharmaceutical, PET imaging can provide quantitative information regarding blood flow (H2 15O), hypoxia (18F-misonidazole), DNA metabolism (11C-thymidine; 18F-fluorothymidine), glucose metabolism (18F-2-fluoro-2-deoxy-D-glucose), protein synthesis rate (11C-tyrosine), amino acid metabolism (11C-methionine), and receptor status. A major advance in PET has been the advent of a new generation of imaging tools combining a PET and a CT module in one camera. This allows the simultaneous acquisition of a whole body CT and PET during one single imaging session. The resulting coregistered whole-body PET-CT images allow a perfect integration of the metabolism with the structural and morphologic characteristics of the disease. This new modality has been used increasingly for clinical oncologic imaging since 2001.

The clinical added-value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG PET) in the management of oncology patients is increasingly documented. In the present review, we discuss both the benefits and the limitations of 18FDG PET in different cancers. Considering the literature data and our own experience, we also indicate the best clinical approach to optimize the use of metabolic imaging in oncology.

Background: The presence of bone-seeking radiopharmaceutical uptake in extraskeletal tissues of the lower or upper extremities may indirectly reflect the presence of active inflammatory lesions in patients in whom systemic disease is suspected. Materials and Methods: The authors present the case of a 26-year-old woman who had mixed signs of scleroderma and cosinophilic fasciitis, in whom misleading findings on planar bone scintigraphy suggested diffuse muscular tracer uptake in the lower extremities. Results: However, using additional SPECT imaging of the pelvis and thighs, it was shown that the soft tissue radioactivity was clearly restricted to the fascia overlying the muscles. The fascial localization of the inflammation was confirmed by biopsy. Conclusion: SPECT imaging was proven useful in indicating the exact localization of an active inflammatory process in the muscle fascia.

Purpose of review Positron emission tomography using 1 8 F-fluoro-2-deoxy-D-glucose ( 1 8 FDG-PET) is well established in clinical routine as a metabolism-based whole-body imaging tool for cancer diagnosis and follow-up. Several reports have appeared indicating the potential and limitations of this technique in head and neck cancer (HNC). This review limits its scope to the recent advances using 1 8 FDG-PET in the clinical management of HNC. Recent findings The combination of 1 8 FDG-PET and sentinel node biopsy has been explored for the surgical treatment planning of oral and oropharyngeal cancer. Recent reports indicate that multimodality imaging combining PET with high-end CT scanning increases the diagnostic accuracy. 1 8 FDG-PET has a potential for use in radiation treatment planning and for the prediction of response and early evaluation of treatment efficacy. Increasingly 1 8 FDG-PET is used as a clinical imaging modality in the different stages of the management of HNC. In particular, its clinical value in initial staging of neck lymph nodes and in the evaluation of recurrent or residual idsease is well established. In these settings 1 8 FDG-PET has been shown to be more accurate than conventional imaging. Recent studies indicate that 1 8 FDG-PET could be of additional value in staging the NO neck, in radiation treatment planning, and in prediction of treatment efficacy.

In a famous article published in the 1991 April issue of The Journal of Nuclear Medicine, Henry N. Wagner announced: “Clinical PET; its time has come” [1]. During the 1990s, the added value of F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) in the assessment of various kinds of cancers was firmly established [2]. In recent years, an increasing number of reports have also indicated the potential of metabolic imaging in patients with systemic inflammatory diseases [3]. Both clinical entities (i.e. cancer and inflammation) may have some neurotropism [4, 5]. In daily practice, however, no clear guidelines exist with regard to the limits of PETacquisition. As a rule, areas located outside the brain are systematically scanned in routine whole-body PET, while the incorporation of the brain varies considerably from one centre to another. In the present paper, we address some of the clinical reasons that may warrant the elective inclusion of the brain in routine whole-body FDG PET. We also suggest technical procedures that may help in implementing the acquisition of whole-body plus brain PET. Cancer

This study aimed to evaluate tumour hypoxia by comparing [(18)F]Fluoromisonidazole uptake measured using positron emission tomography ([(18)F]FMISO-PET) with immunohistochemical (IHC) staining techniques. Syngeneic rhabdomyosarcoma (R1) tumour pieces were transplanted subcutaneously in the flanks of WAG/Rij rats. Tumours were analysed at volumes between 0.9 and 7.3 cm(3). Hypoxic volumes were defined using a 3D region of interest on 2 h postinjection [(18)F]FMISO-PET images, applying different thresholds (1.2-3.0). Monoclonal antibodies to pimonidazole (PIMO) and carbonic anhydrase IX (CA IX), exogenous and endogenous markers of hypoxia, respectively, were used for IHC staining. Marker-positive fractions were microscopically measured for each tumour, and hypoxic volumes were calculated. A heterogeneous distribution of hypoxia was observed both with histology and [(18)F]FMISO autoradiography. A statistically significant correlation (P, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

To determine the salivary function, after parotid-sparing radiotherapy (RT), of different regions within the parotid gland and to evaluate dose-function relationships within the parotid glands and between patients.Sixteen head and neck cancer patients, irradiated between September 1999 and November 2000 using a conformal parotid-sparing technique, were included in this study. Before RT and 7 months after RT (range 6-10 months), a salivary gland scintigraphy was performed in all patients combined with a single photon emission computed tomography (SPECT). The salivary excretion fraction (SEF) was measured, after stimulation, in 8-12 transverse 5mm SPECT slices of each parotid. Loss of salivary excretion fraction (dSEF %) of these slices was calculated as the proportion of SEF after RT as compared to SEF before RT. Since the planning CT-scan and the SPECT-scintigraphy were performed in the same treatment position, the dose to a transverse slice within the parotid gland could be matched to the loss of salivary excretion fraction of that respective slice. A non-linear model was fitted to the dose-loss of function data and the dose resulting in 50% loss of salivary excretion fraction (D50) was calculated.Before RT, all but one patient presented with normal salivary excretion fractions (SEF) of both parotid glands. Within the same parotid gland, the SEF's of the different slices were almost equal. Seven months after RT, the reduction in SEF was statistically significant (P-value0.0001). A significant difference in loss of salivary excretion fraction (dSEF) was also observed between both parotid glands (P0.0001) as a result of the parotid-sparing technique. When plotting the dSEF of a slice versus the dose given to that slice, doses as low as 10-15 Gy could result in a serious loss of function (dSEF50%). After fitting a non-linear model to these plots, the mean dose resulting in 50% loss of salivary excretion fraction (D50) 7 months after RT was 22.5 Gy. A large inter-patient variability was found in D50.Salivary SPECT is a useful tool for the evaluation of the salivary function of different slices within the parotid gland. Before irradiation, the different slices within one parotid gland act as functional sub-units contributing equally to the function of the entire gland. Seven months after an average dose of 22.5 Gy (D50) the functional sub-unit has lost 50% of its excretion fraction. The high inter-patient variability in D50 and the observation that low doses (10-15 Gy) can induce serious loss of function should prompt us in the clinic to reduce the dose to the parotids even lower than the threshold of 22.5 Gy.

18F-fluorodeoxyglucose (FDG) and 11C-methionine (MET) PET imaging studies allow the investigation of metabolism and amino acid transport in brain tumours. Their (relative) usefulness and prognostic value in suspected recurrence or progression of primary brain tumours after previous therapy is an issue of debate. The aim of this study was to compare directly both radioligands in this setting. Cerebral uptake of FDG and MET was determined sequentially on the same day in 30 patients (21 males, nine females; age 40.4±15.6 years), on average 4.0 years (range 0.1–18) after therapy for a primary brain tumour (23 grade II–IV astrocytomas, four oligodendrogliomas and three mixed oligo-astrocytomas). Images were acquired on a Siemens HR+ dedicated PET camera. Two observers scored FDG and MET scans independently. Semi-quantitative indices defined by the tumour (maximum)-to-background ratio were calculated based on manual ROI delineation and by using MET ROIs for FDG after automated co-registration. Patient follow-up was conducted until the last contact with inconspicuous clinical findings (average 41 months, range 12–62 months after PET) [(n=10)] or until death (n=20). Overall median survival was 15.0 months. MET showed pathologically increased uptake in 28/30 scans, and FDG in 17/30. The inter-observer agreement was 100% for MET and 73% for FDG. Using Kaplan-Meier survival analysis, significant differences were found for both FDG (cut-off 0.8, log-rank p=0.007) and MET (cut-off 2.2, log-rank p=0.014). The combination of FDG and MET information resulted in the highest prognostic accuracy (p=0.003), while MET alone was the best prognostic predictor in the subgroup of patients with primary astrocytoma (n=23). FDG and MET PET studies provide complementary prognostic information in patients with suspected brain tumour recurrence or progression after primary therapy. MET is considered the single agent of choice in the evaluation of these patients because of its sensitivity and clearer delineation of the suspected recurrence.