MRI and 18F-FET PET for Multimodal Treatment Monitoring in Patients with Brain Metastases: A Cost-Effectiveness Analysis.

PET using the radiolabeled amino acid O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) has been shown to be of value for treatment monitoring in patients with brain metastases after multimodal therapy, especially in clinical situations with equivocal MRI findings. As medical procedures must be justified socioeconomically, we determined the effectiveness and cost-effectiveness of 18F-FET PET for treatment monitoring of multimodal therapy, including checkpoint inhibitors, targeted therapies, radiotherapy, and combinations thereof in patients with brain metastases secondary to melanoma or non-small cell lung cancer. Methods: We analyzed already-published clinical data and calculated the associated costs from the German statutory health insurance system perspective. Two clinical scenarios were considered: decision tree model 1 determined the effectiveness of 18F-FET PET alone for identifying treatment-related changes, that is, the probability of correctly identifying patients with treatment-related changes confirmed by neuropathology or clinicoradiographically using the Response Assessment in Neuro-Oncology criteria for immunotherapy. The resulting cost-effectiveness ratio showed the cost for each correctly identified patient with treatment-related changes in whom MRI findings remained inconclusive. Decision tree model 2 calculated the effectiveness of both 18F-FET PET and MRI, that is, the probability of correctly identifying nonresponders to treatment. The incremental cost-effectiveness ratio was calculated to determine cost-effectiveness, that is, the cost for each additionally identified nonresponder by 18F-FET PET who would have remained undetected by MRI. One-way deterministic and probabilistic sensitivity analyses tested the robustness of the results. Results: 18F-FET PET identified 94% of patients with treatment-related changes, resulting in €1,664.23 (€1.00 = $1.08 at time of writing) for each correctly identified patient. Nonresponders were correctly identified in 60% by MRI and in 80% by 18F-FET PET, resulting in €3,292.67 and €3,915.83 for each correctly identified nonresponder by MRI and 18F-FET PET, respectively. The cost to correctly identify 1 additional nonresponder by 18F-FET PET, who would have remained unidentified by MRI, was €5,785.30. Conclusion: Given the considerable annual cost of multimodal therapy, the integration of 18F-FET PET can potentially improve patient care while reducing costs.

Assessment of Brain Tumour Perfusion Using Early-Phase 18F-FET PET: Comparison with Perfusion-Weighted MRI.

PURPOSE: Morphological imaging using MRI is essential for brain tumour diagnostics. Dynamic susceptibility contrast (DSC) perfusion-weighted MRI (PWI), as well as amino acid PET, may provide additional information in ambiguous cases. Since PWI is often unavailable in patients referred for amino acid PET, we explored whether maps of relative cerebral blood volume (rCBV) in brain tumours can be extracted from the early phase of PET using O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET). PROCEDURE: Using a hybrid brain PET/MRI scanner, PWI and dynamic 18F-FET PET were performed in 33 patients with cerebral glioma and four patients with highly vascularized meningioma. The time interval from 0 to 2 min p.i. was selected to best reflect the blood pool phase in 18F-FET PET. For each patient, maps of MR-rCBV, early 18F-FET PET (0-2 min p.i.) and late 18F-FET PET (20-40 min p.i.) were generated and coregistered. Volumes of interest were placed on the tumour (VOI-TU) and normal-appearing brain (VOI-REF). The correlation between tumour-to-brain ratios (TBR) of the different parameters was analysed. In addition, three independent observers evaluated MR-rCBV and early 18F-FET maps (18F-FET-rCBV) for concordance in signal intensity, tumour extent and intratumoural distribution. RESULTS: TBRs calculated from MR-rCBV and 18F-FET-rCBV showed a significant correlation (r = 0.89, p < 0.001), while there was no correlation between late 18F-FET PET and MR-rCBV (r = 0.24, p = 0.16) and 18F-FET-rCBV (r = 0.27, p = 0.11). Visual rating yielded widely agreeing findings or only minor differences between MR-rCBV maps and 18F-FET-rCBV maps in 93 % of the tumours (range of three independent raters 91-94%, kappa among raters 0.78-1.0). CONCLUSION: Early 18F-FET maps (0-2 min p.i.) in gliomas provide similar information to MR-rCBV maps and may be helpful when PWI is not possible or available. Further studies in gliomas are needed to evaluate whether 18F-FET-rCBV provides the same clinical information as MR-rCBV.

99mTc­labeled single-domain antibody for SPECT/CT assessment of HER2 expression in diverse cancer types.

The expression status of human epidermal growth factor receptor 2 (HER2) in cancer predicts response to HER2-targeted therapy. Therefore, its accurate determination is of utmost importance. In recent years, there has been an increase in research on noninvasive techniques for molecular imaging, as this method offers the advantages of a more accurate determination of HER2 status without the need for multiple biopsies. The technetium-labeled single-domain antibody RAD201, previously known as 99mTc-NM-02, has been shown to be safe for use in breast cancer imaging with reasonable radiation doses, favorable biodistribution, and imaging characteristics. METHODS: A total of six HER2-positive, heavily pretreated patients with different cancer types aged between 42 and 69 years (5 women and 1 man; the median age of 55.5) have been examined. In six of seven scans, the patients were administered 500 ml of Gelofusine® solution (40 mg/ml) for radiation protection before the tracer injection (434 ± 42 MBq). Planar scans were acquired with the patient supine at 10 min, 60 min, 160 min, 20 h, and 24 h after injection. A CT scan was acquired at 95 min, followed by local tomographic SPECT imaging. RESULTS: One patient was scanned twice with RAD201, 3 months apart, resulting in a total of seven scans for six patients. Here, we show that the use of RAD201 in our patient group shows the same favorable biodistribution as in a previous study with RAD201 (NCT04040686) and that the radiation dose to the critical organ kidney can be reduced by the application of the plasma expander Gelofusine® by almost 50%. CONCLUSION: RAD201 appears safe for use in humans and is a promising noninvasive tool for discriminating HER2 status in metastatic (breast) cancer, regardless of ongoing HER2-targeted antibody treatment.

Assessment of the lymphatic system by indirect lymphography in patients with post-thrombotic syndrome.

OBJECTIVE: Alterations in lower extremity lymph drainage caused by chronic venous obstruction (CVO) have not been well studied, partially because of a lack of standardized imaging modalities to assess the quality of lymphatic drainage in the lower extremities of patients with post-thrombotic syndrome (PTS). However, these changes are likely to have an impact on the severity of the disease and clinical outcomes of interventions. In the present study, we investigated the feasibility and diagnostic value of preintervention indirect lymphography in patients with CVO and their pre- and postintervention Villalta scores. METHODS: A total of 17 patients (21 limbs) with iliofemoral and caval CVO were included in the study between 2017 and 2018. The deep and superficial lymphatic vessels in both legs were assessed before venous recanalization and stenting. The quality of lymphatic flow was compared between the legs with CVO and healthy legs. Moreover, the correlation between the lymphatic changes and clinical severity of PTS was evaluated using the Villalta score and CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) classification. RESULTS: The mean patient age was 44 ± 12 years, and 10 patients (59%) were women. The patients had undergone treatment at a mean of 25 ± 6 months after their first episode of deep vein thrombosis. Five patients (29%) had had recurrent deep vein thrombosis. The mean pre- and postinterventional Villalta score was 10.5 ± 1.46 and 9.27 ± 1.12, respectively (P = .0096). Using the CEAP classification, four legs were class 5, seven were class 4, and three each were class 3 and 2. The primary and secondary patency rate was 70.5% and 82.5% after a mean follow-up of 18 months, respectively. Indirect lymphography of the superficial and deep lymphatic systems was completed before intervention in both legs for all 17 patients (21 legs). According to the qualitative criteria, abnormal lymphatic vessel function was found in 35.2% of the superficial and 58.8% of the deep lymphatic vessels of the affected legs. Further analysis revealed abnormal function of the deep lymphatic vessels in all patients with moderate to severe PTS according to the Villalta score. CONCLUSIONS: Indirect lymphography is a feasible diagnostic tool to use for the evaluation of the function of lymphatic vessels. Impaired drainage of the deep lymphatic system was found in all our patients with moderate to severe PTS. The clinical significance of these lymphatic changes is not clear; however, an association between clinical severity and outcomes is possible.

Evaluation of SPECT/CT in the assessment of inflammatory jaw pathologies.

PURPOSE: Since accurate diagnosis of inflammatory jaw diseases is still challenging, this study investigated the performance of three phase bone scintigraphy including SPECT/CT in the assessment of correct diagnosis and size of the affected bone tissue. METHOD: This retrospective study contained 31 patients with suspected jaw-related osteoradionecrosis, osteomyelitis or medication-related osteonecrosis of the jaw, which underwent 3-phase bone scintigraphy including SPECT/CT. Results were reviewed by two nuclear medicine physicians. Positive cases received surgery; negative ones were followed-up for six months. Both served as reference standard. Inflamed bone length was measured in the SPECT/CT images and postoperatively by a pathologist. RESULTS: 19 out of 20 positive cases and 10 out of 11 negative ones were classified correctly by SPECT/CT (sensitivity 95 %, specificity 91 %, accuracy 94 %, positive predictive value 95 %, negative predictive value 91 %). Regarding the length of affected bone, no significant difference (p = 0.23) could be observed between SPECT/CT and postoperative obtained values. Both correlated significantly (r = 0.86, p = 0.0001). CONCLUSION: SPECT/CT can safely detect different kinds of inflammatory jaw pathologies compared to other conventional imaging modalities. Lack of specificity of conventional scintigraphy ranging from 17 % to 71 % in earlier studies could be improved by adding CT-analysis. Additionally, SPECT/CT assists the surgeon in determining the expansion of the process (with focus on the length) preoperatively and thereby optimizing surgery planning.

Assessment of Chemotherapy-Induced Organ Damage with Ga-68 Labeled Duramycin.

PURPOSE: Evaluation of [68Ga]NODAGA-duramycin as a positron emission tomography (PET) tracer of cell death for whole-body detection of chemotherapy-induced organ toxicity. PROCEDURES: Tracer specificity of Ga-68 labeled NODAGA-duramycin was determined in vitro using competitive binding experiments. Organ uptake was analyzed in untreated and doxorubicin, busulfan, and cisplatin-treated mice 2 h after intravenous injection of [68Ga]NODAGA-duramycin. In vivo data were validated by immunohistology and blood parameters. RESULTS: In vitro experiments confirmed specific binding of [68Ga]NODAGA-duramycin. Organ toxicities were detected successfully using [68Ga]NODAGA-duramycin PET/X-ray computed tomography (CT) and confirmed by immunohistochemistry and blood parameter analysis. Organ toxicities in livers and kidneys showed similar trends in PET/CT and immunohistology. Busulfan and cisplatin-related organ toxicities in heart, liver, and lungs were detected earlier by PET/CT than by blood parameters and immunohistology. CONCLUSION: [68Ga]NODAGA-duramycin PET/CT was successfully applied to non-invasively detect chemotherapy-induced organ toxicity with high sensitivity in mice. It, therefore, represents a promising alternative to standard toxicological analyses with a high translational potential.

[Development of a national competency-based learning objective catalogue for undergraduate medical education in Germany]. / Entwicklung eines kompetenzbasierten Lernzielkatalogs Nuklearmedizin für das Studium der Humanmedizin in Deutschland.

AIMS: Implementation of the guidelines on the Competency-based Learning Objective Catalogue for Undergraduate Medical Education for a Nuclear Medicine curriculum on behalf of the committee on professional training and continuing education of the German Association of Nuclear Medicine (DGN) METHODS:: In 7 domains 100 learning objectives (LOs) were subject to a prioritization in 3 categories (A, B and C) by means of a questionnaire as part of a Delphi method, in collaboration with all members of the DGN holding a "venia legendi" as experts. Category A defined the essential LOs for each medical practitioner. The prioritization was made by ranking the frequency of the A-classifications. In the 2nd step of the Delphi method, a list of LOs with the ranking positions 1-5 in each domain was presented to the first round's experts as a core curriculum, asking either for acceptance or modifications. RESULTS: The results of the 1st step of the Delphi method deliver a return rate of 29% of the questionnaires (55 out of 184). The 2nd round shows a return rate of 30.9% (57 out of 184) and full approval of the proposed LOs in all LO domains by in median 72 % of the experts consulted (61%-81%). The present final version contains 37 competency-based LOs in the LO domains "legal basis and radiation protection", "basic science", indications and contra-indications for "PET/CT", "scintigraphy and SPECT", "patient preparation", "image interpretation" as well as "therapy". CONCLUSION: The Competency-based Learning Objective Catalogue for Nuclear Medicine describes the knowledge and competencies, every physician should have at the end of his medical studies. The LO catalogue is a living document, which needs to be adapted continuously to the progress of the medical and technological development.

O-(2-18F-fluoroethyl)-L-tyrosine PET for evaluation of brain metastasis recurrence after radiotherapy: an effectiveness and cost-effectiveness analysis.

BACKGROUND: Conventional MRI is the standard method to diagnose recurrence of brain metastases after radiation. However, following radiation therapy, reactive transient blood-brain barrier alterations with consecutive contrast enhancement can mimic brain metastasis recurrence. Recent studies have suggested that O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET improves the correct differentiation of brain metastasis recurrence from radiation injury. Based on published evidence and clinical expert opinion, we analyzed effectiveness and cost-effectiveness of the use of FET PET in addition to MRI compared with MRI alone for the diagnosis of recurrent brain metastases. METHODS: A decision-tree model was designed to compare the 2 diagnostic strategies from the perspective of the German Statutory Health Insurance (SHI) system. Effectiveness was defined as correct diagnosis of recurrent brain metastasis and was compared between FET PET with MRI and MRI alone. Costs were calculated for a baseline scenario and for a more expensive scenario. Robustness of the results was tested using sensitivity analyses. RESULTS: Compared with MRI alone, FET PET in combination with MRI increases the rate of correct diagnoses by 42% (number needed to diagnose of 3) with an incremental cost-effectiveness ratio of €2821 (baseline scenario) and €4014 (more expensive scenario) per correct diagnosis. The sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: The model suggests that the additional use of FET PET with conventional MRI for the diagnosis of recurrent brain metastases may be cost-effective. Integration of FET PET has the potential to avoid overtreatment with corresponding costs as well as unnecessary side effects.

Quantitative assessment of Zirconium-89 labeled cetuximab using PET/CT imaging in patients with advanced head and neck cancer: a theragnostic approach.

Biomarkers predicting treatment response to the monoclonal antibody cetuximab in locally advanced head and neck squamous cell carcinomas (LAHNSCC) are lacking. We hypothesize that tumor accessibility is an important factor in treatment success of the EGFR targeting drug. We quantified uptake of cetuximab labeled with Zirconium-89 (89Zr) using PET/CT imaging.Seventeen patients with stage III-IV LAHNSCC received a loading dose unlabeled cetuximab, followed by 10 mg 54.5±9.6 MBq 89Zr-cetuximab. PET/CT images were acquired either 3 and 6 or 4 and 7 days post-injection. 89Zr-cetuximab uptake was quantified using standardized uptake value (SUV) and tumor-to-background ratio (TBR), and correlated to EGFR immunohistochemistry. TBR was compared between scan days to determine optimal timing.Uptake of 89Zr-cetuximab varied between patients (day 6-7: SUVpeak range 2.5-6.2). TBR increased significantly (49±28%, p < 0.01) between first (1.1±0.3) and second scan (1.7±0.6). Between groups with a low and high EGFR expression a significant difference in SUVmean (2.1 versus 3.0) and SUVpeak (3.2 versus 4.7) was found, however, not in TBR. Data is available at www.cancerdata.org (DOI: 10.17195/candat.2016.11.1).In conclusion, 89Zr-cetuximab PET imaging shows large inter-patient variety in LAHNSCC and provides additional information over FDG-PET and EGFR expression. Validation of the predictive value is recommended with scans acquired 6-7 days post-injection.

Thyroid nodules with indeterminate cytology: molecular imaging with 99mTc-methoxyisobutylisonitrile (MIBI) is more cost-effective than the Afirma gene expression classifier.

PURPOSE: To compare the cost-effectiveness of (99m)Tc-methoxyisobutylisonitrile (MIBI) thyroid scintigraphy and the Afirma gene expression classifier for the assessment of cytologically indeterminate thyroid nodules. METHODS: A decision tree model was used. Costs were calculated from the perspective of the German health insurance system. The robustness of the results was assessed with probabilistic sensitivity analyses using a Monte Carlo simulation. RESULTS: Life expectancy was 34.3 years (estimated costs per patient €1,459 - €2,224) for the MIBI scan and 34.1 years (estimated costs €3,560 - €4,071) for the molecular test. These results were confirmed by the Monte Carlo simulation. CONCLUSION: MIBI thyroid scintigraphy is more cost-effective than the gene expression classifier.

Body surface area adapted iopromide 300 mg/ml versus 370 mg/ml contrast medium injection protocol: influence on quantitative and clinical assessment in combined PET/CT.

PURPOSE: To investigate the quantitative and qualitative differences between combined positron emission tomography and computed X-ray tomography (PET/CT) enhanced with contrast medium with either an iodine concentration 300 mg/ml or 370 mg/ml. MATERIALS AND METHODS: 120 consecutive patients scheduled for F-18-Fluorodeoxyglucose (FDG) PET/CT were included. The first (second) 60 patients received contrast medium with 300 (370) mg iodine/ml. Intravenous injection protocols were adapted for an identical iodine delivery rate (1.3mg/s) and body surface area (BSA) adapted iodine dose (22.26 gI/m(2)). Maximum and mean standardized uptake values (SUV(max); SUV(mean)) and contrast enhancement (HU) were determined in the ascending aorta, the abdominal aorta, the inferior vena cava, the portal vein, the liver and the right kidney in the venous contrast medium phase. PET data were evaluated visually for the presence of malignancy and image quality. RESULTS: Both media caused significantly higher values for HU, SUV(mean) and SUV(max) for the enhanced PET/CT than the non-enhanced one (all p<0.01). There were no significant differences in the degree of increase of HU, SUV(mean) and SUV(max) between the two contrast media at any anatomic site (all p>0.05). Visual evaluation of lesions showed no differences between contrast and non-contrast PET/CT or between the two different contrast media (p=0.77). CONCLUSION: When using a constant iodine delivery rate and total iodine dose in a BSA adapted injection protocol, there are no quantitative or qualitative differences in either CT or PET between contrast media with an iodine concentration of 300 mg/ml and 370 mg/ml, respectively.

The influence of different contrast medium concentrations and injection protocols on quantitative and clinical assessment of FDG-PET/CT in lung cancer.

OBJECTIVES: To compare the effects of two different contrast medium concentrations for use in computed X-ray tomography (CT) employing two different injection protocols on positron emission tomography (PET) reconstruction in combined 2-(18)F-desoxyglucose (FDG) PET/CT in patients with a suspicion of lung cancer. METHODS: 120 patients with a suspicion of lung cancer were enrolled prospectively. PET images were reconstructed with the non-enhanced and venous phase contrast CT obtained after injection of iopromide 300 mg/ml or 370 mg/ml using either a fixed-dose or a body surface area adapted injection protocol. Maximum and mean standardized uptake values (SUV(max) and SUV(mean)) and contrast enhancement (HU) were determined in the subclavian vein, ascending aorta, abdominal aorta, inferior vena cava, portal vein, liver and kidney and in the suspicious lung lesion. PET data were evaluated visually for the presence of malignancy and image quality. RESULTS: At none of the sites a significant difference in the extent of the contrast enhancement between the four different protocols was found. However, the variability of the contrast enhancement at several anatomical sites was significantly greater in the fixed dose groups than in the BSA groups for both contrast medium concentrations. At none of the sites a significant difference was found in the extent of the SUV(max) and SUV(mean) increase as a result of the use of the venous phase contrast enhanced CT for attenuation. Visual clinical evaluation of lesions showed no differences between contrast and non-contrast PET/CT (P=0.32). CONCLUSIONS: Contrast enhanced CT for attenuation correction in combined PET/CT in lung cancer affects neither the clinical assessment nor image quality of the PET-images. A body surface adapted contrast medium protocol reduces the interpatient variability in contrast enhancement.

The use of O-(2-18F-fluoroethyl)-L-tyrosine PET for treatment management of bevacizumab and irinotecan in patients with recurrent high-grade glioma: a cost-effectiveness analysis.

UNLABELLED: To date, the use of structural MR imaging (including contrast-enhanced and T2-weighted or fluid-attenuated inversion recovery-weighted images) is the standard method to diagnose tumor progression and to assess antiangiogenic treatment effects. However, several studies have suggested that O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET adds valuable clinical information to the information derived from structural MR imaging alone. We evaluated the effectiveness and cost-effectiveness of the addition of (18)F-FET PET to structural MR imaging for the management of treatment with bevacizumab and irinotecan (BEV/IR) in patients with recurrent high-grade glioma compared with MR imaging alone from the perspective of the German Statutory Health Insurance. METHODS: To evaluate the incremental cost-effectiveness of the additional use of (18)F-FET PET, a decision tree model was used. Effectiveness of (18)F-FET PET was defined as correct identification of both tumor progression before BEV/IR treatment initiation and BEV/IR treatment response and was evaluated for the combination of (18)F-FET PET and MR imaging compared with MR imaging alone. Costs were estimated for a baseline scenario and for a more expensive scenario. The robustness of the results was tested using deterministic and probabilistic sensitivity analyses. RESULTS: The use of (18)F-FET PET resulted in a number needed to diagnose of 2.4, that is, 3 additional patients have to be diagnosed to avoid 1 wrong diagnosis. The incremental cost-effectiveness ratio of (18)F-FET PET/MR imaging compared with MR imaging alone was €5,725 (€1 ≈ $1.30) for the baseline scenario and €8,145 for the more expensive scenario per additional correct diagnosis. The probabilistic sensitivity analysis confirmed the robustness of the results. CONCLUSION: The model suggests that the additional use of (18)F-FET PET in the management of patients with recurrent high-grade glioma treated with BEV/IR may be cost-effective. Integration of (18)F-FET PET has the potential to avoid overtreatment and corresponding costs, as well as unnecessary side effects to the patient.

Different intravenous contrast media concentrations do not affect clinical assessment of 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans in an intraindividual comparison.

OBJECTIVE: The purpose of this study was to perform an intraindividual comparison of the influences of different iodine contrast media on tracer uptake, contrast enhancement, and image quality in combined positron emission tomography (PET)/computed tomography (CT). MATERIALS AND METHODS: Fifty-one patients underwent baseline and follow-up combined PET/CT consisting of low-dose unenhanced and venous contrast-enhanced CT with contrast media containing a high concentration of iodine (iopromide, 370 mg/mL) and a standard iodine concentration (iopromide, 300 mg/mL). The total iodine load (44.4 g) and the iodine delivery rate (1.29 g/s) were identical for the 2 protocols. The mean and maximum standard uptake values, as measures of tracer uptake and contrast enhancement for unenhanced and contrast-enhanced PET/CT, were quantified at 10 different anatomical sites, and images were analyzed for clinically relevant differences. RESULTS: The mean and maximum standard uptake values were significantly increased in contrast-enhanced PET/CT compared with unenhanced PET/CT at each anatomical site (P < 0.05). Comparison of tracer uptake between the 300- and 370-mg iodine contrast media showed no significant differences (all P > 0.05). Comparison of contrast enhancement between the 300- and 370-mg iodine contrast media showed no significant difference at any anatomical site (all P > 0.05). Analysis of image quality revealed no clinically relevant differences between the 2 different iodine contrast media (P = 0.739). CONCLUSION: The use of contrast-enhanced CT scans for attenuation correction in PET/CT does not cause clinically relevant artifacts in PET scan reconstruction, regardless of the iodine concentration used. Standard- and high-iodine contrast media can be used equivalently.

PET/CT in lung cancer: Influence of contrast medium on quantitative and clinical assessment.

OBJECTIVES: To evaluate the influence of intravenous contrast medium and different contrast medium phases on attenuation correction, PET image quality and clinical staging in combined PET/CT in patients with a suspicion of lung cancer. METHODS: Sixty patients with a suspicion of lung cancer were prospectively enrolled for combined (18)F-FDG-PET/CT examination. PET images were reconstructed with non-enhanced and arterial and venous phase contrast CT. Maximum and mean standardised uptake values (SUVmax and SUVmean) and contrast enhancement (HU) were determined in the subclavian vein, ascending aorta, abdominal aorta, inferior vena cava, portal vein, liver and kidney and lung tumour. PET data were evaluated visually for clinical staging and image quality. RESULTS: SUVmax was significantly increased between contrast and non-contrast PET/CT at all anatomic sites (all P < 0.001). SUVmax was significantly increased for arterial PET/CT compared to venous PET/CT in the arteries (all P < 0.001). Venous PET/CT resulted in significantly higher SUVmax values compared to arterial PET/CT in the parenchymatous organs (all P < 0.05). Visual clinical evaluation of malignant lesions showed no differences between contrast and non-contrast PET/CT (P = 1.0). CONCLUSIONS: Contrast enhanced CT is suitable for attenuation correction in combined PET/CT in lung cancer; it affects neither the clinical assessment nor image quality of the PET images. KEY POINTS : • Positron emission tomography combined with computed tomography is now a mainstream investigation • There has been debate about whether CT contrast agents affect PET results • Contrast-enhanced CT is satisfactory for attenuation correction in lung cancer PET/CT • Multiphase CT does not affect PET; additional unenhanced CT is unnecessary • For quantitative follow-up PET analysis, an identical PET/CT protocol is required.

Multiphase CT scanning and different intravenous contrast media concentrations in combined F-18-FDG PET/CT: Effect on quantitative and clinical assessment.

PURPOSE: To evaluate the influence of multiphase CT scanning and different intravenous contrast media on contrast enhancement, attenuation correction and image quality in combined PET/CT. MATERIAL AND METHODS: 140 patients were prospectively enrolled for F-18-FDG-PET/CT including a low-dose unenhanced, arterial and venous contrast enhanced CT. The first (second) 70 patients, received contrast medium with 370 (300) mg iodine/ml. The iodine delivery rate (1.3mg/s) and total iodine load (44.4g) were identical for both groups. Contrast enhancement and maximum and mean standardized FDG uptake values (SUVmax and SUVmean) were determined for the un-enhanced, arterial and venous PET/CT at multiple anatomic sites and PET reconstructions were visually evaluated. RESULTS: Arterial contrast enhancement was significantly higher for the 300mg/ml contrast medium compared to 370mgI/ml at all anatomic sites. Venous enhancement was not different between the two contrast media. SUVmean and SUVmax were significantly higher for the contrast enhanced compared to the non-enhanced PET/CT at all anatomic sites (all P<0.001). Tracer uptake was significantly higher in the arterial than in the venous PET/CT in the arteries using both contrast media (all P<0.001). No differences in tracer uptake were found between the contrast media (all P>0.05). Visual assessment revealed no relevant differences between the different PET reconstructions. CONCLUSIONS: There is no relevant qualitative influence on the PET scan from the use of different intravenous contrast media in its various phases in combined multiphase PET/CT. For quantitative analysis of tracer uptake it is required to use an identical PET/CT protocol.

A phantom assessment of portable imaging and radio-guided surgery systems with technetium-99m and fluorine-18.

AIM: To perform a detailed analysis of the performance of mobile intraoperative imaging systems and gamma probes in a phantom set-up, and compare this with a conventional gamma camera. METHODS: Two separate experiments were performed. In the first, a modified Jaszczak phantom equipped with five (99m)Tc-filled hot spheres (0.5-20 ml) was analyzed using Sentinella, declipseSPECT and a conventional gamma camera under three conditions: no background, spheres on the surface of the background activity, and totally immersed spheres (contrast level in both 1: 8). In the second experiment, two phantom spheres (0.5 and 2 ml) filled with (99m)Tc and (18)F (infinite contrast, 1: 4 and 1: 8) were measured using the hand-held probes Navigator and GammaLocator DXI. Data analysis consisted of signal-to-background ratios and determination of the full-width at half-maximum (FWHM). A visual scoring was performed by three nuclear medicine physicians. RESULTS: At infinite contrast, (99m)Tc-filled spheres with volumes of at least 2 ml could be detected adequately with all systems (e.g. 2 ml sphere, FWHM: ECAM 11 mm, declipseSPECT 9 mm, Navigator 13 mm, GammaLocator 12 mm). Under decreased contrast conditions, the results for all systems were impaired and the 0.5 ml phantom sphere filled with either (99m)Tc or (18)F was only detected accurately by the GammaLocator (FWHM range: 13-17 mm). CONCLUSION: All systems are suitable for intraoperative sentinel node detection with nearly infinite signal-to-background contrast. At a lower contrast, the GammaLocator performed best for the detection of small volumes at low-contrast ratios regardless of the radionuclide.

Failure of annexin-based apoptosis imaging in the assessment of antiangiogenic therapy effects.

BACKGROUND: Molecular apoptosis imaging is frequently discussed to be useful for monitoring cancer therapy. We demonstrate that the sole assessment of therapy effects by apoptosis imaging can be misleading, depending on the therapy effect on the tumor vasculature. METHODS: Apoptosis was investigated by determining the uptake of Annexin Vivo by optical imaging (study part I) and of 99 mTc-6-hydrazinonicotinic [HYNIC]-radiolabeled Annexin V by gamma counting (study part II) in subcutaneous epidermoid carcinoma xenografts (A431) in nude mice after antiangiogenic treatment (SU11248). Optical imaging was performed by optical tomography (3D) and 2D reflectance imaging (control, n = 7; therapy, n = 6). Accumulation of the radioactive tracer was determined ex vivo (control, n = 5; therapy, n = 6). Tumor vascularization was investigated with an optical blood pool marker (study part I) and contrast-enhanced ultrasound (both studies). Data were validated by immunohistology. RESULTS: A significantly higher apoptosis rate was detected in treated tumors by immunohistological terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining (area fraction: control, 0.023 ± 0.015%; therapy, 0.387 ± 0.105%; P < 0.001). However, both 2D reflectance imaging using Annexin Vivo (control, 13 ± 15 FI/cm2; therapy, 11 ± 7 FI/cm2) and gamma counting using 99 mTc-HYNIC-Annexin V (tumor-to-muscle ratio control, 5.66 ± 1.46; therapy, 6.09 ± 1.40) failed in showing higher accumulation in treated tumors. Optical tomography even indicated higher probe accumulation in controls (control, 81.3 ± 73.7 pmol/cm3; therapy, 27.5 ± 34.7 pmol/cm3). Vascularization was strongly reduced after therapy, demonstrated by contrast-enhanced ultrasound, optical imaging, and immunohistology. CONCLUSIONS: The failure of annexin-based apoptosis assessment in vivo can be explained by the significant breakdown of the vasculature after therapy, resulting in reduced probe/tracer delivery. This favors annexin-based apoptosis imaging only in therapies that do not severely interfere with the vasculature.

Cost-effectiveness of hybrid PET/CT for staging of non-small cell lung cancer.

UNLABELLED: Although the diagnostic effectiveness of integrated PET/CT for staging of non-small cell lung cancer (NSCLC) has already been proven, it remains to be determined if tumor staging with combined metabolic and anatomic imaging is also cost-effective. The objective of this study was to evaluate from a payers' perspective the cost-effectiveness of staging NSCLC with CT alone (representing the mainstay diagnostic test) and with integrated PET/CT. METHODS: The study is based on 172 NSCLC patients from a prospective clinical study who underwent diagnostic, contrast-enhanced helical CT and integrated PET/CT. Imaging was performed at the University Hospital Ulm between May 2002 and December 2004. To calculate treatment costs, we differentiated among cost for diagnosis, cost for nonsurgical treatment according to the clinical diagnosis, and cost for surgical procedures according to the clinical tumor stage. RESULTS: The diagnostic effectiveness in terms of correct TNM staging was 40% (31/77) for CT alone and 60% (46/77) for PET/CT. For the assessment of resectability (tumor stages Ia-IIIa vs. IIIb-IV), 65 of 77 patients (84%) were staged correctly by PET/CT (CT alone, 70% [54/77]). The incremental cost-effectiveness ratios per correctly staged patient were $3,508 for PET/CT versus CT alone. The incremental cost-effectiveness ratios per quality-adjusted life year gained were $79,878 for PET/CT vs. CT alone, decreasing to $69,563 assuming a reduced loss of utility (0.10 quality-adjusted life years) due to surgical morbidity. CONCLUSION: Cost-effectiveness analyses showed that costs for PET/CT are within the commonly accepted range for diagnostic tests or therapies. Therefore, reimbursement of PET/CT for NSCLC staging can be also recommended from an economic point of view.