Altered biodistribution of [68Ga]Ga-DOTA-TOC during somatostatin analogue treatment.

PURPOSE: The need for an interval between the administration of long-acting Somatostatin Receptor Analogues (SSA) and the [68Ga]Ga-DOTA-TATE PET has been questioned based on recent literature in the new EANM guidelines. Here an earlier studies showed that SSA injection immediately before SSTR PET had minimal effect on normal organ and tumor uptake (1). However, data are scarce and there are (small) differences between [68Ga]Ga-DOTA-TATE and [68Ga]Ga-DOTA-TOC binding affinity, and it remains unknown whether these findings can be directly translated to scans with [68Ga]Ga-DOTA-TOC as well. The purpose of this study was to assess the effect of SSA use on the biodistribution in a subsequent [68Ga]Ga-DOTA-TOC PET/CT and compare this intra-individually across several cycles of SSA treatments. METHODS: Retrospectively, 35 patients with NENs were included. [68Ga]Ga-DOTA-TOC PET at staging and after the 1st and 2nd cycle of SSA were included. SUVmean and SUVmax of blood, visceral organs, primary tumor and two metastases were determined. Also, the interval between SSA therapy and the PET scan was registered. RESULTS: Treatment with SSA resulted in a significantly higher bloodpool activity and lower visceral tracer uptake. This effect was maintained after a 2nd cycle of SSA therapy. Furthermore, there was an inverse relationship between bloodpool tracer availability and visceral tracer binding and a positive correlation between bloodpool tracer availability and primary tumor tracer uptake. With an interval of up to 5 days, there was a significantly higher bloodpool activity than at longer intervals. CONCLUSION: Absolute comparison of the SUV on [68Ga]Ga-DOTA-TOC PET should be done with caution as the altered biodistribution of the tracer after SSA treatment should be taken into account. We recommend not to perform a scan within the first 5 days after the injection of lanreotide.

Radiomics for precision medicine: Current challenges, future prospects, and the proposal of a new framework.

The advancement of artificial intelligence concurrent with the development of medical imaging techniques provided a unique opportunity to turn medical imaging from mostly qualitative, to further quantitative and mineable data that can be explored for the development of clinical decision support systems (cDSS). Radiomics, a method for the high throughput extraction of hand-crafted features from medical images, and deep learning -the data driven modeling techniques based on the principles of simplified brain neuron interactions, are the most researched quantitative imaging techniques. Many studies reported on the potential of such techniques in the context of cDSS. Such techniques could be highly appealing due to the reuse of existing data, automation of clinical workflows, minimal invasiveness, three-dimensional volumetric characterization, and the promise of high accuracy and reproducibility of results and cost-effectiveness. Nevertheless, there are several challenges that quantitative imaging techniques face, and need to be addressed before the translation to clinical use. These challenges include, but are not limited to, the explainability of the models, the reproducibility of the quantitative imaging features, and their sensitivity to variations in image acquisition and reconstruction parameters. In this narrative review, we report on the status of quantitative medical image analysis using radiomics and deep learning, the challenges the field is facing, propose a framework for robust radiomics analysis, and discuss future prospects.

[Lutetium-177-PSMA radioligand therapy : Consensus within the framework of GKV-funded care between the university hospitals in Aachen, Bonn, Düsseldorf, Essen, and Cologne and the MDK Nordrhein]. / Lutetium-177-PSMA-Radioligandentherapie : Konsensus im Rahmen der GKV-finanzierten Versorgung zwischen den Hochschulkliniken in Aachen, Bonn, Düsseldorf, Essen und Köln und dem MDK Nordrhein.

In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.

Added value of dedicated axillary hybrid 18F-FDG PET/MRI for improved axillary nodal staging in clinically node-positive breast cancer patients: a feasibility study.

PURPOSE: To investigate the feasibility and potential added value of dedicated axillary 18F-FDG hybrid PET/MRI, compared to standard imaging modalities (i.e. ultrasound [US], MRI and PET/CT), for axillary nodal staging in clinically node-positive breast cancer. METHODS: Twelve patients with clinically node-positive breast cancer underwent axillary US and dedicated axillary hybrid 18F-FDG PET/MRI. Nine of the 12 patients also underwent whole-body PET/CT. Maximum standardized uptake values (SUVmax) were measured for the primary breast tumor and the most FDG-avid axillary lymph node. A positive axillary lymph node on dedicated axillary hybrid PET/MRI was defined as a moderate to very intense FDG-avid lymph node. The diagnostic performance of dedicated axillary hybrid PET/MRI was calculated by comparing quantitative and its qualitative measurements to results of axillary US, MRI and PET/CT. The number of suspicious axillary lymph nodes was subdivided as follows: N0 (0 nodes), N1 (1-3 nodes), N2 (4-9 nodes) and N3 (≥ 10 nodes). RESULTS: According to dedicated axillary hybrid PET/MRI findings, seven patients were diagnosed with N1, four with N2 and one with N3. With regard to mean SUVmax, there was no significant difference in the primary tumor (9.0 [±5.0] vs. 8.6 [±5.7], p = 0.678) or the most FDG-avid axillary lymph node (7.8 [±5.3] vs. 7.7 [±4.3], p = 0.767) between dedicated axillary PET/MRI and PET/CT. Compared to standard imaging modalities, dedicated axillary hybrid PET/MRI resulted in changes in nodal status as follows: 40% compared to US, 75% compared to T2-weighted MRI, 40% compared to contrast-enhanced MRI, and 22% compared to PET/CT. CONCLUSIONS: Adding dedicated axillary 18F-FDG hybrid PET/MRI to diagnostic work-up may improve the diagnostic performance of axillary nodal staging in clinically node-positive breast cancer patients.

Correction to: 18F-NaF PET/CT: EANM procedure guidelines for bone imaging.

The original version of this article unfortunately contained an error. The name and affiliation of "Frédéric Paycha" needs to be corrected. Given in this article is the correct author name and affiliation.

Quantitative performance evaluation of 124I PET/MRI lesion dosimetry in differentiated thyroid cancer.

The aim was to investigate the quantitative performance of 124I PET/MRI for pre-therapy lesion dosimetry in differentiated thyroid cancer (DTC). Phantom measurements were performed on a PET/MRI system (Biograph mMR, Siemens Healthcare) using 124I and 18F. The PET calibration factor and the influence of radiofrequency coil attenuation were determined using a cylindrical phantom homogeneously filled with radioactivity. The calibration factor was 1.00 ± 0.02 for 18F and 0.88 ± 0.02 for 124I. Near the radiofrequency surface coil an underestimation of less than 5% in radioactivity concentration was observed. Soft-tissue sphere recovery coefficients were determined using the NEMA IEC body phantom. Recovery coefficients were systematically higher for 18F than for 124I. In addition, the six spheres of the phantom were segmented using a PET-based iterative segmentation algorithm. For all 124I measurements, the deviations in segmented lesion volume and mean radioactivity concentration relative to the actual values were smaller than 15% and 25%, respectively. The effect of MR-based attenuation correction (three- and four-segment µ-maps) on bone lesion quantification was assessed using radioactive spheres filled with a K2HPO4 solution mimicking bone lesions. The four-segment µ-map resulted in an underestimation of the imaged radioactivity concentration of up to 15%, whereas the three-segment µ-map resulted in an overestimation of up to 10%. For twenty lesions identified in six patients, a comparison of 124I PET/MRI to PET/CT was performed with respect to segmented lesion volume and radioactivity concentration. The interclass correlation coefficients showed excellent agreement in segmented lesion volume and radioactivity concentration (0.999 and 0.95, respectively). In conclusion, it is feasible that accurate quantitative 124I PET/MRI could be used to perform radioiodine pre-therapy lesion dosimetry in DTC.

Molecularly targeted therapies in cancer: a guide for the nuclear medicine physician.

Molecular imaging continues to influence every aspect of cancer care including detection, diagnosis, staging and therapy response assessment. Recent advances in the understanding of cancer biology have prompted the introduction of new targeted therapy approaches. Precision medicine in oncology has led to rapid advances and novel approaches optimizing the use of imaging modalities in cancer care, research and development. This article focuses on the concept of targeted therapy in cancer and the challenges that exist for molecular imaging in cancer care.

Pharmacokinetic modeling of a novel hypoxia PET tracer [18F]HX4 in patients with non-small cell lung cancer.

BACKGROUND: [18F]HX4 is a promising new PET tracer developed to identify hypoxic areas in tumor tissue. This study analyzes [18F]HX4 kinetics and assesses the performance of simplified methods for quantification of [18F]HX4 uptake. To this end, eight patients with non-small cell lung cancer received dynamic PET scans at three different time points (0, 120, and 240 min) after injection of 426 ± 72 MBq [18F]HX4, each lasting 30 min. Several compartment models were fitted to time activity curves (TAC) derived from various areas within tumor tissue using image-derived input functions. RESULTS: Best fits were obtained using the reversible two-tissue compartment model with blood volume parameter (2T4k+VB). Simplified measures correlated well with VT estimates (tumor-to-blood ratio (TBr) R 2 = 0.96, tumor-to-muscle ratio R 2 = 0.94, standardized uptake value R 2 = 0.89). CONCLUSIONS: [18F]HX4 shows reversible kinetics in tumor tissue: 2T4k+VB. TBr based on static imaging at 2 or 4 h can be used for quantification of [18F]HX4 uptake.

Patients with high-risk differentiated thyroid cancer have a lower I-131 ablation success rate than low-risk ones in spite of a high ablation activity.

OBJECTIVE: To examine success rates in strictly defined high-risk differentiated thyroid cancer (DTC) patients who received a high-activity (≥5550 MBq) adjuvant postoperative I-131 therapy and compare these to the rates found in highest risk and low-risk patients. DESIGN: Retrospective database study. PATIENTS: We examined 377 patients with DTC who received I-131 ablation. Patients with distant metastases were classified as very high risk. Patients with primary tumours >4 cm, extensive extrathyroidal invasion (pT4a or pT4b in accordance with the 7th edition of the TNM system), and patients with ≥5 lymph node metastases or any lateral compartment lymph node metastases were considered high risk. All other patients were considered low risk. MEASUREMENTS: Ablation success rate at first TSH-stimulated follow-up. RESULTS: The ablation success rate was 72·6% in low-risk patients, 51·7% in high-risk patients and 13·8% in highest risk patients (all differences P < 0·001). In none of the groups, a significant difference in the initial I-131 activity was found between patients with successful and unsuccessful ablation (low risk: P = 0·16, high risk: P = 0·91 and highest risk: P = 0·48). Furthermore, there was no difference in ablation success between patients who received <5550 MBq and those who received ≥5550 Mbq (low risk: P = 0·31, high risk: P = 0·69 and highest risk: P = 0·22). CONCLUSIONS: Patients with high-risk DTC have a significantly reduced I-131 ablation success rate compared to low-risk ones in spite of high initial I-131 activities. As successful ablation is prognostically important, efforts should be made to improve outcome in these patients.

The EANM practice guidelines for bone scintigraphy.

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

Diagnosis and Treatment of Nasopharyngeal Carcinoma in Children and Adolescents - Recommendations of the GPOH-NPC Study Group.

Nasopharyngeal carcinoma (NPC) is a rare malignant tumor arising from epithelial cells of the nasopharynx. Its incidence is highest in Southeast Asia. Age distribution of NPC is bimodal, with one peak in young adolescents and another in patients 55-59 years of age. EBV appears to be the primary etiologic agent in the pathogenesis, environmental factors such as nitrosamines and genetic factors are contributory. NPC is most commonly diagnosed in locally advanced stages, with lymph node metastases occurring in up to 90% of patients. About 5-10% of patients present with distant metastases. Diagnosis of NPC is made histologically, supported by an abnormal anti-EBV-VCA IgA titer and elevated plasma EBV-DNA load. Superior results in children and adolescents with advanced locoregional NPC, with overall and event-free survival rates>90%, have been achieved by neoadjuvant chemotherapy with 5-fluoruracil and cisplatin, followed by synchronous radiochemotherapy and subsequent maintenance therapy with interferon-ß as demonstrated by the 2 prospective studies GPOH-NPC-91 and -2003. Response to therapy can be assessed by PET-imaging and in patients with complete remission after neoadjuvant chemotherapy, the radiation dose to the primary tumor can be safely reduced from 59.4 to 54.4 Gy. Since the majority of long term sequalae such as xerostomia, skin and tissue fibrosis are caused by high radiation dosages, radiotherapy modalities such as intensity-modulated radiotherapy should be used to efficiently spare non-tumorous tissue. For patients with metastatic disease and relapse, survival chances are low. New treatment strategies, such as the application of EBV-specific T-lymphocytes should be considered for these patients.

Comparison of diagnostic accuracy of (111)In-pentetreotide SPECT and (68)Ga-DOTATOC PET/CT: A lesion-by-lesion analysis in patients with metastatic neuroendocrine tumours.

OBJECTIVES: To compare the diagnostic accuracy of (111)In-pentetreotide-scintigraphy with (68)Ga-DOTATOC-positron emission tomography (PET)/computed tomography (CT) in patients with metastatic-neuroendocrine tumour (NET) scheduled for peptide receptor radionuclide therapy (PRRT). Incremental lesions (ILs) were defined as lesions observed on only one modality. METHODS: Fifty-three metastatic-NET-patients underwent (111)In-pentetreotide-scintigraphy (24 h post-injection; planar+single-photon emission CT (SPECT) abdomen) and whole-body (68)Ga-DOTATOC-PET/CT. SPECT and PET were compared in a lesion-by-lesion and organ-by-organ analysis, determining the total lesions and ILs for both modalities. RESULTS: Significantly more lesions were detected on (68)Ga-DOTATOC-PET/CT versus (111)In-pentetreotide-scintigraphy. More specifically, we observed 1,098 lesions on PET/CT (range: 1-105; median: 15) versus 660 on SPECT (range: 0-73, median: 9) (p<0.0001), with 439 PET-ILs (42/53 patients) and one SPECT-IL (1/53 patients). The sensitivity for PET/CT was 99.9 % (95 % CI, 99.3-100.0), for SPECT 60.0 % (95 % CI, 48.5-70.2). The organ-by-organ analysis showed that the PET-ILs were most frequently visualized in liver and skeleton. CONCLUSION: Ga-DOTATOC-PET/CT is superior for the detection of NET-metastases compared to (111)In-pentetreotide SPECT. KEY POINTS: Somatostatin receptor PET is superior to SPECT in detecting NET metastases. PET is the scintigraphic method for accurate depiction of NET tumour burden. The sensitivity of PET is twofold higher than the sensitivity of SPECT.

Clinical value of 68Ga-DOTATATE-PET/CT compared to stand-alone contrast enhanced CT for the detection of extra-hepatic metastases in patients with neuroendocrine tumours (NET).

PURPOSE: To compare and outline the beneficial skills of combined (68)Ga-DOTATATE positron emission tomography (PET) with concurrent contrast enhanced X-ray computed tomography (ceCT) against stand-alone ceCT in 54 patients with neuroendocrine tumours (NET). METHODS: Patients with histologically confirmed NET and available follow-up of at least 6 months (median 12.6 months; range 6.1-23.2) were included. PET/CT and ceCT images were initially analyzed separately by two blinded nuclear medicine physicians and two radiologists, respectively. In a second step all four physicians reviewed all detected lesions together reaching a consensus-grading for PET/ceCT. The results were then compared to the reference standard consisting of clinical follow-up data. RESULTS: With regard to true positive lesions, PET/ceCT vs. stand alone ceCT detected 139 vs. 48 bone-lesions, 106 vs. 71 lymph node metastases and 26 vs. 26 pulmonary lesions. On a per-patient basis, PET/ceCT achieved a higher sensitivity (100% vs. 47%) and specificity (89% vs. 49%) for bone lesions than ceCT. For lymph nodes the effect was similar (sensitivity 92% vs. 64% and specificity 83% vs. 59%). For the detection of pulmonary lesions the sensitivity was identical (100%) while specificity of PET/ceCT was superior to ceCT-alone (95% vs. 82%). CONCLUSION: In summary, the use of (68)Ga-DOTATATE PET/ceCT leads to an increase in sensitivity and specificity in the detection of extra-hepatic NET metastases compared to stand-alone ceCT. Therefore, (68)Ga-DOTATATE PET/ceCT should be the imaging modality of choice in patients with NET.

Low brown adipose tissue activity in endurance-trained compared with lean sedentary men.

BACKGROUND/OBJECTIVES: It has now been unequivocally demonstrated that humans possess functional brown adipose tissue (BAT) and that human BAT can be recruited upon chronic cold stimulation. Recruitment of BAT has been postulated as a potential strategy to counteract the current global obesity epidemic. Recently, it was shown in rodents that endurance exercise training could stimulate the recruitment of brown-like adipocytes within white adipose tissue (WAT) via exercise-induced myokines such as irisin (the cleaved circulating product of the type 1 membrane protein FNDC5) and interleukin-6 (IL-6). Our objective was to test whether endurance-trained athletes had increased cold-stimulated BAT activity and browning of subcutaneous WAT compared with lean sedentary males. SUBJECTS/METHODS: Twelve endurance-trained athletes and 12 lean sedentary males were measured during 2 h of mild cold exposure to determine cold-induced BAT activity via [(18)F]fluorodeoxyglucose-positron emission tomography-computed tomography ([(18)F]FDG-PET-CT) scanning. Skeletal muscle FNDC5 expression, as well as plasma irisin and IL-6 levels were determined. In addition, a subcutaneous abdominal WAT biopsy was taken to measure gene expression of several markers for browning of WAT. RESULTS: Cold-induced BAT activity was significantly lower in athletes, and no differences in gene expression of classical brown and beige adipocyte markers were detected in subcutaneous WAT between the groups. As expected, mRNA expression of FNDC5 in skeletal muscle was significantly higher in endurance athletes but plasma irisin and Il-6 levels were similar in both groups. CONCLUSIONS: These results indicate that chronic endurance exercise is not associated with brown and beige adipocyte recruitment; in fact endurance training appears to be linked to lower the metabolic activity of BAT in humans.

(18)F-NaF PET/CT: EANM procedure guidelines for bone imaging.

The aim of this guideline is to provide minimum standards for the performance and interpretation of (18)F-NaF PET/CT scans. Standard acquisition and interpretation of nuclear imaging modalities will help to provide consistent data acquisition and numeric values between different platforms and institutes and to promote the use of PET/CT modality as an established diagnostic modality in routine clinical practice. This will also improve the value of scientific work and its contribution to evidence-based medicine.

Timing of post 131I ablation diagnostic whole body scan in differentiated thyroid cancer patients. Less than four months post ablation may be too early.

AIM: to determine whether the first three months after 131I ablation is too early to perform radioiodine diagnostic whole body scintigraphy (dxWBS) in differentiated thyroid carcinoma patients. PATIENTS, MATERIAL, METHODS: The files of 462 patients who were treated for DTC in our hospital were reviewed. All patients underwent surgical thyroidectomy. 146 patients had data available on a. a dxWBS which was performed less than four months (max 120 days) after 131I ablation with concurrent stimulated TSH stimulated thyroglobulin (Tg) measurement without further therapeutic measures between ablation and dxWBS and b. a second dxWBS or 131I therapy (rxWBS) within 1.5 years after ablation. RESULTS: A discordance between the initial and follow-up scan was found in 25/129 (19%) patients: of 54 patients with a positive initial dxWBS, scan results of a second dxWBS or rxWBS obtained with a suitable distance to the initial scan contradicted the initial one in 15 patients (27%). New lesions were discovered in 10/74 negative first dxWBS cases (14%). A discordance between the initial and follow-up stimulated Tg was found in 5/129 (4%) patients: 2/90 (2%) of patients with a negative stimulated Tg at initial dxWBS subsequently showed a positive results whereas 3/29 (10%) patients with an initially positive Tg showed a negative Tg level at the second procedure. CONCLUSION: Less than four months after 131I ablation is too early to perform radioiodine diagnostic whole body scintigraphy with concurrent TSH stimulated Tg measurement. The identification of the right, later, timepoint however requires further research.

No evidence for attenuated stress-induced extrastriatal dopamine signaling in psychotic disorder.

Stress is an important risk factor in the etiology of psychotic disorder. Preclinical work has shown that stress primarily increases dopamine (DA) transmission in the frontal cortex. Given that DA-mediated hypofrontality is hypothesized to be a cardinal feature of psychotic disorder, stress-related extrastriatal DA release may be altered in psychotic disorder. Here we quantified for the first time stress-induced extrastriatal DA release and the spatial extent of extrastriatal DA release in individuals with non-affective psychotic disorder (NAPD). Twelve healthy volunteers (HV) and 12 matched drug-free NAPD patients underwent a single infusion [(18)F]fallypride positron emission tomography scan during which they completed the control and stress condition of the Montreal Imaging Stress Task. HV and NAPD did not differ in stress-induced [(18)F]fallypride displacement and the spatial extent of stress-induced [(18)F]fallypride displacement in medial prefrontal cortex (mPFC) and temporal cortex (TC). In the whole sample, the spatial extent of stress-induced radioligand displacement in right ventro-mPFC, but not dorso-mPFC or TC, was positively associated with task-induced subjective stress. Psychotic symptoms during the scan or negative, positive and general subscales of the Positive and Negative Syndrome Scale were not associated with stress-induced [(18)F]fallypride displacement nor the spatial extent of stress-induced [(18)F]fallypride displacement in NAPD. Our results do not offer evidence for altered stress-induced extrastriatal DA signaling in NAPD, nor altered functional relevance. The implications of these findings for the role of the DA system in NAPD and stress processing are discussed.