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.

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.

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.

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.

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.

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.

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.

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.

Automatic, three-segment, MR-based attenuation correction for whole-body PET/MR data.

PURPOSE: The combination of positron emission tomography (PET) and magnetic resonance (MR) tomography in a single device is anticipated to be the next step following PET/CT for future molecular imaging application. Compared to CT, the main advantages of MR are versatile soft tissue contrast and its capability to acquire functional information without ionizing radiation. However, MR is not capable of measuring a physical quantity that would allow a direct derivation of the attenuation values for high-energy photons. METHODS: To overcome this problem, we propose a fully automated approach that uses a dedicated T1-weighted MR sequence in combination with a customized image processing technique to derive attenuation maps for whole-body PET. The algorithm automatically identifies the outer contour of the body and the lungs using region-growing techniques in combination with an intensity analysis for automatic threshold estimation. No user interaction is required to generate the attenuation map. RESULTS: The accuracy of the proposed MR-based attenuation correction (AC) approach was evaluated in a clinical study using whole-body PET/CT and MR images of the same patients (n = 15). The segmentation of the body and lung contour (L-R directions) was evaluated via a four-point scale in comparison to the original MR image (mean values >3.8). PET images were reconstructed using elastically registered MR-based and CT-based (segmented and non-segmented) attenuation maps. The MR-based AC showed similar behaviour as CT-based AC and similar accuracy as offered by segmented CT-based AC. Standardized uptake value (SUV) comparisons with reference to CT-based AC using predefined attenuation coefficients showed the largest difference for bone lesions (mean value ± standard variation of SUV(max): -3.0% ± 3.9% for MR; -6.5% ± 4.1% for segmented CT). A blind comparison of PET images corrected with segmented MR-based, CT-based and segmented CT-based AC afforded identical lesion detectability, but slight differences in image quality were found. CONCLUSION: Our MR-based attenuation correction method offers similar correction accuracy as offered by segmented CT. According to the specialists involved in the blind study, these differences do not affect the diagnostic value of the PET images.

Brain metastasis in lung cancer. Comparison of cerebral MRI and 18F-FDG-PET/CT for diagnosis in the initial staging.

UNLABELLED: FDG-PET/CT is increasingly used in staging of lung cancer as single "one stop shop" method. AIM, PATIENTS, METHODS: We prospectively included 104 neurological asymptomatic patients (65 years, 26% women) with primary diagnosis of lung cancer. In all patients PET/CT including cerebral imaging and cerebral MRI were performed. RESULTS: Diagnosis of brain metastases (BM) was made by PET/CT in 8 patients only (7.7%), by MRI in 22 (21.2%). In 80 patients both PET/CT and MRI showed no BM. In 6 patients (5.8%) BM were detectable on PET/CT as well as on MRI. Exclusive diagnosis of BM by MRI with negative finding on PET/CT was present in 16 patients (15.4%). 2 patients (1.9%) had findings typical for BM on PET/CT but were negative on MRI. With MRI overall 100 BM were detected, with PET/CT only 17 BM (p < 0.01). For the diagnosis of BM PET/CT showed a sensitivity of 27.3%, specificity of 97.6%, positive predictive value of 75% and negative predictive value of 83.3%. BM diameter on PET/CT and MRI were consistent in 43%, in 57% BM were measured larger on MRI. DISCUSSION: Compared to the gold standard of MRI for cerebral staging a considerable number of patients are falsely diagnosed as free from BM by PET/CT. MRI is more accurate than PET/CT for detecting multiple and smaller BM. CONCLUSION: In patients with a curative option MRI should be performed additionally to PET/CT for definitive exclusion of brain metastases.

Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.

AIM: The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. METHODS: Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. RESULTS: Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. CONCLUSION: The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.

A novel presenilin1 mutation (Q223R) associated with early onset Alzheimer's disease, dysarthria and spastic paraparesis and decreased Abeta levels in CSF.

BACKGROUND AND PURPOSE: A novel presenilin1 (PSEN1) mutation associated with dementia and spastic paraplegia in a family with five affected individuals is described. The index patient was a 35-year-old man presenting with cognitive decline, behavioural symptoms, dysarthria, and gait disorder due to spasticity. METHODS AND RESULTS: Genetic analysis revealed a missense mutation Gln223Arg in exon 7. Initial CSF analysis revealed drastically decreased Abeta42 level despite marginally decreased FDG metabolism. CONCLUSION: Cerebrospinal fluid biomarker analysis might point towards genetic analysis of PSEN1 in patients with positive family history and age of onset below 60 years.

Molecular imaging of prostate cancer.

Prostate carcinoma is the most common non-cutaneous malignancy in males. Imaging of prostatic lesions is of great importance and aids in oncologic management and monitoring of therapy response. Particularly molecular imaging based on positron emission tomography (PET) and single photon emission computerized tomography (SPECT) has great potential. Using radio-labelled molecular probes, these approaches are highly sensitive and can provide key molecular and functional information on tumours. The identification of suitable targets based on unique genetic and biochemical features of cancer lesions is one of the core activities driving progress in molecular imaging of pathological processes. Nowadays, mainly metabolic probes are being used routinely for detection and staging of prostate cancer. The development of new specific receptor ligands and targeted probes and antibodies holds great promise to further enhance the performance of molecular imaging and to further improve the diagnosis and monitoring of prostate cancer.

[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.