68Ga-PSMA-PET/CT-directed IGRT/SBRT for oligometastases of recurrent prostate cancer after initial surgery.

Background: We evaluated efficacy and toxicity of 68Ga-PSMA-Positron Emission Tomography/Computed Tomography (PET/CT)-directed stereotactic body radiotherapy and image-guided radiotherapy (SBRT/IGRT) for oligometastases of prostate cancer recurrences after previous surgery.Methods: Nineteen patients were analyzed within a prospective PET-registry study (064/2013BO1) and retrospectively analyzed (807/2017BO2) fulfilling the following inclusion criteria: biochemical recurrence after radical prostatectomy, ≤five 68Ga-PSMA-PET/CT positive lesions. Biochemical control was evaluated with EORTC (European Organization for Research and Treatment of Cancer)- and Phenix-definitions. Toxicity was scored according to CTCAE-criteria v. 4.03.Results: A total of 38 oligometastases (19 patients, 2 with re-treatment) were treated with SBRT/IGRT from October 2014 to July 2017. 68Ga-PSMA-PET/CT-positive lesions were detected on average 39 months (5-139) after prostatectomy (pT2b-3b pN0-1 cM0). Mean PSA (Prostate-specific antigen)-level at time of imaging reached 2.2 ng/mL (range 0.2-10.1). PET/CT-positive lesions were treated with different fractionation schedules reaching biological equivalent doses (BED) of 116.7-230.0 Gy. Concomitant androgen deprivation therapy (ADT) was given in seven patients. After a median follow-up of 17 months (4-42) all patients were alive. Estimated 1-year PSA- control (n = 19) reached 80.8% (Phenix) and 67.5% (EORTC). A PSA-decline (≥50%) was detected in 16/19 patients after radiotherapy. Higher graded G3+-acute toxicity did not occur. Temporary late G3-proctitis was detected in one patient.Conclusions: Reaching of nadir ≤0.1 or 0.2 ng/mL was associated by improved DMFS (distant metastases free survival) and could serve as a surrogate endpoint for RT of oligometastases after initial prostatectomy. Short term effects of 68Ga-PSMA-PET/CT-based ablative radiotherapy for oligometastases demonstrated an acceptable toxicity profile and favorable biochemical response.

Two decades of SPECT/CT - the coming of age of a technology: An updated review of literature evidence.

PURPOSE: Single-photon emission computed tomography (SPECT) combined with computed tomography (CT) was introduced as a hybrid SPECT/CT imaging modality two decades ago. The main advantage of SPECT/CT is the increased specificity achieved through a more precise localization and characterization of functional findings. The improved diagnostic accuracy is also associated with greater diagnostic confidence and better inter-specialty communication. METHODS: This review presents a critical assessment of the relevant literature published so far on the role of SPECT/CT in a variety of clinical conditions. It also includes an update on the established evidence demonstrating both the advantages and limitations of this modality. CONCLUSIONS: For the majority of applications, SPECT/CT should be a routine imaging technique, fully integrated into the clinical decision-making process, including oncology, endocrinology, orthopaedics, paediatrics, and cardiology. Large-scale prospective studies are lacking, however, on the use of SPECT/CT in certain clinical domains such as neurology and lung disorders. The review also presents data on the complementary role of SPECT/CT with other imaging modalities and a comparative analysis, where available.

Assessment of metastatic colorectal cancer with hybrid imaging: comparison of reading performance using different combinations of anatomical and functional imaging techniques in PET/MRI and PET/CT in a short case series.

PURPOSE: The purpose was to investigate the diagnostic performance of different combinations of anatomical and functional imaging techniques in PET/MRI and PET/CT for the evaluation of metastatic colorectal cancer lesions. METHODS: Image data of 15 colorectal cancer patients (FDG-PET/CT and subsequent FDG-PET/MRI) were retrospectively evaluated by two readers in five reading sessions: MRI (morphology) alone, MRI/diffusion-weighted MRI (DWI), MRI/PET, MRI/DWI/PET; and PET/CT. Diagnostic performance of lesion detection with each combination was assessed in general and organ-based. The reference standard was given by histology and/or follow-up imaging. Separate analysis of mucinous tumours was performed. RESULTS: One hundred and eighty lesions (110 malignant) were evaluated (intestine n = 6, liver n = 37, lymph nodes n = 55, lung n = 4, and peritoneal n = 74). The overall lesion-based diagnostic accuracy was 0.46 for MRI, 0.47 for MRI/DWI, 0.57 for MRI/PET, 0.69 for MRI/DWI/PET and 0.66 for PET/CT. In the organ-based assessment, MRI/DWI/PET showed the highest accuracy for liver metastases (0.74), a comparable accuracy to PET/CT in peritoneal lesions (0.55), and in lymph node metastases (0.84). The accuracy in mucinous tumour lesions was limited in all modalities (MRI/DWI/PET = 0.52). CONCLUSIONS: PET/MRI including DWI is comparable to PET/CT in the evaluation of colorectal cancer metastases, with a markedly higher accuracy when using combined imaging data than the modalities separately. Further improvement is needed in the imaging of peritoneal carcinomatosis and mucinous tumours.

[Molecular imaging in neurological diseases]. / Molekulare Bildgebung bei neurologischen Erkrankungen.

In neurodegeneration and in neuro-oncology, the standard imaging procedure, magnetic resonance imaging (MRI), shows limited sensitivity and specificity. Molecular imaging with specific positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers allows various molecular targets and metabolic processes to be assessed and is thus a valuable adjunct to MRI. Two important examples are referred to here: amino acid transport for neuro-oncological issues, and the recently approved PET tracers for detecting amyloid depositions during the preclinical stage of Alzheimer's disease. This review discusses the clinical relevance and indications for the following nuclear medicine imaging procedures: amyloid PET, (18)F-fluorodeoxyglucose (FDG)-PET, and dopamine transporter (DaT)-SPECT for the diagnosis of dementia and the differential diagnosis of Parkinson's disease, in addition to amino acid PET for the diagnosis of brain tumors and somatostatin receptor imaging in meningioma.

[Simultaneous whole-body PET-MRI in pediatric oncology : More than just reducing radiation?]. / Simultane Ganzkörper-PET-MRT in der pädiatrischen Onkologie : Mehr als nur Strahlenersparnis?

Diagnostic imaging plays an essential role in pediatric oncology with regard to diagnosis, therapy-planning, and the follow-up of solid tumors. The current imaging standard in pediatric oncology includes a variety of radiological and nuclear medicine imaging modalities depending on the specific tumor entity. The introduction of combined simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) has opened up new diagnostic options in pediatric oncology. This novel modality combines the excellent anatomical accuracy of MRI with the metabolic information of PET. In initial clinical studies, the technical feasibility and possible diagnostic advantages of combined PET-MRI have been in comparison with alternative imaging techniques. It was shown that a reduction in radiation exposure of up to 70 % is achievable compared with PET-CT. Furthermore, it has been shown that the number of imaging studies necessary can be markedly reduced using combined PET-MRI. Owing to its limited availability, combined PET-MRI is currently not used as a routine procedure. However, this new modality has the potential to become the imaging reference standard in pediatric oncology in the future. This review article summarizes the central aspects of pediatric oncological PET-MRI based on existing literature. Typical pediatric oncological PET-MRI cases are also presented.

[Relapsing polychondritis. Primary and follow-up diagnostics with (18)F-FDG-PET/CT]. / Rezidivierende Polychondritis. Primär- und Verlaufsdiagnostik mittels (18)F-FDG-PET/CT.

CASE REPORT: This article presents an overview of the typical clinical and imaging features of relapsing polychondritis (RP), a rare autoimmune disease, based on a case report CONCLUSION: Although the diagnosis is mainly established clinically, the use of (18)F fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG-PET/CT) has been proven to be a useful diagnostic tool to accurately determine the extent of inflammation throughout the body [corrected]. Furthermore (18)F-FDG-PET/CT provides a high sensitivity for detection of a relapse, especially when clinical and laboratory results are inconclusive. Additionally, (18)F-FDG-PET/CT helps to assess disease activity during the course of therapy.

[PET-MR in patients with glioblastoma multiforme]. / PET-MR bei Patienten mit Glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common and most aggressive primary tumor of the brain. In recent years newer therapeutic approaches have been developed. To allow for an optimized treatment planning it is important to precisely delineate necrotic tissue, edema and vital tumor tissue and to identify the most aggressive parts of the GBM. The magnetic resonance (MR) portion of an MR-positron emission tomography (PET) examination in patients with GBM should consist of both structural and functional sequences including diffusion-weighted and perfusion sequences. The use of (18)F-fluorodeoxyglucose ((18)F-FDG) is limited in patients with gliomas as glucose metabolism is already physiologically high in parts of the brain but (18)F-FDG is nevertheless a commonly used radiopharmaceutical for neuro-oncological questions. (18)F-fluorothymidine reflects the cellular activity of thymidine kinase 1 and correlates with the expression of KI-67 as an index of mitotic activity. The nitroimidazole derivatives (18)F-fluoromisonidazole and (18)F-fluoroazomycin arabinoside ((18)F-FAZA) allow the detection of hypoxic areas within the tumor. In recent years amino acid tracers, such as (18)F-fluoroethyltyrosine are increasingly being used in the diagnosis of gliomas. The simultaneous PET-MR image acquisition allows new approaches, e.g. motion correction by the simultaneous acquisition of MR data with a high temporal resolution and an improved quantification of the PET signal by integrating the results of functional MR sequences. Moreover, the simultaneous acquisition of these two time-consuming methods leads to reduced imaging times for this, often severely ill patient group.

Impact of the maximum ring difference on image quality and noise characteristics of a total-body PET/CT scanner.

The sensitivity of a PET system highly depends on the axial acceptance angle or maximum ring difference (MRD), which can be particularly high for total-body scanners due to their larger axial field of views (aFOVs). This study aims to evaluate the impact on image quality (IQ) and noise performance when MRD85 (18°), the current standard for clinical use, is increased to MRD322 (52°) for the Biograph Vision Quadra (Siemens Healthineers). METHODS: Studies with a cylindrical phantom covering the 106 cm aFOV and an IEC phantom filled with 18F, 68Ga and 89Zr were performed for acquisition times from 60 to 1800 s and activity concentrations from 0.4 to 3 kBq/ml to assess uniformity, contrast recovery coefficients (CRCs) and to characterize noise by coefficient of variation (CV). Spatial resolution was compared for both MRDs by sampling a quadrant of the FOV with a point source. Further IQ, CV, liver SUVmean and SUVmax were compared for a cohort of 5 patients scanned with [18F]FDG (3 MBq/kg, 1 h p.i.) from 30 to 300 s. RESULTS: CV was improved by a factor of up to 1.49 and is highest for short acquisition times, peaks at the center field of view and mitigates parabolic in axial direction with no difference to MRD85 beyond the central 80 cm. No substantial differences between the two evaluated MRDs in regards to uniformity, SUVmean or CRC for the different isotopes were observed. A degradation of the average spatial resolution of 0.9 ±â€¯0.2 mm in the central 40 cm FOV was determined with MRD322. Depending on the acquisition time MRD322 resulted in a decrease of SUVmax between 23.8% (30 s) and 9.0% (300 s). CONCLUSION: Patient and phantom studies revealed that scan time could be lowered by approximately a factor of two with MRD322 while maintaining similar noise performance. The moderate degradation in spatial resolution for MRD322 is worth to exploit the full potential of the Quadra by either shorten scan times or leverage noise performance in particular for low count scenarios such as ultra-late imaging or dynamic studies with high temporal resolution.

Dual-isotope SPECT imaging of striatal dopamine: a comparative study between never-treated and haloperidol-treated first-episode schizophrenic patients.

The aim of this dual-isotope SPECT imaging study was to evaluate striatal dopamine transporter (DAT) and D2 receptor availability in first-episode never-treated and haloperidol-treated schizophrenic patients and whether the availability is associated with psychopathology. Twenty-four inpatients with a first acute schizophrenic episode were enrolled in the study; 12 of these patients were treated with haloperidol for 2 weeks before dual-isotope SPECT was performed, whereas the other 12 patients underwent the SPECT evaluation directly after enrollment. Twelve healthy control persons were also recruited and evaluated with the dual-isotope SPECT protocol. Psychopathology was assessed by the Positive and Negative Syndrome Scale and other scales. D2-radioligand binding did not differ between drug-naïve patients and the control group but was significantly lower in the haloperidol-treated group. DAT availability was also significantly lower in the haloperidol patients than in the other two groups and differed significantly between drug-naïve, positive-syndrome-type patients and healthy controls. The data obtained with the new dual-isotope SPECT technique reveal a direct effect of haloperidol at the D2 and DAT receptor level.

[Neuroimaging of epilepsies]. / Bildgebende Diagnostik der Epilepsien.

Neuroimaging is crucial for the diagnosis of epilepsy, in particular for syndromic diagnosis of focal epilepsies and for presurgical evaluation. We give recommendations on the optimized acquisition of MRI and discuss the principle and role of additional neuroimaging methods including nuclear medicine and image processing.

[PSMA-based theranostics for prostate cancer : From imaging to treatment]. / PSMA-basierte Theranostik beim Prostatakarzinom : Von der Bildgebung zur Therapie.

BACKGROUND: In recent years nuclear medicine theranostics using radiolabeled prostate-specific membrane antigen (PSMA) ligands have gained increasing importance in the management of prostate cancer. AIM: The aim of this work is to highlight the value of theranostic concepts using radiolabeled PSMA ligands for both the diagnostic work-up and treatment of advanced prostate cancer. MATERIAL AND METHODS: The currently available knowledge in the literature is summarized and presented. RESULTS: The use of PSMA in positron emission tomography-computed tomography (PET/CT) shows a high sensitivity and specificity for prostate cancer imaging, particularly in patients with biochemical recurrences. Furthermore, promising results are also reported for staging of primary prostate cancer and treatment monitoring. In addition, radioligand therapy using alpha and beta emitters is a promising third line treatment option in intensively pretreated patients with metastases. The reduction of side effects and optimization of the treatment sequence of radioligand therapy is of increasing importance. CONCLUSION: Nuclear medicine theranostics have an increasing clinical impact on the diagnostics and treatment of prostate cancer.

PET and SPECT in epilepsy: a critical review.

Molecular imaging with ictal and interictal single-photon emission computed tomography (SPECT) as well as positron emission tomography (PET) rank among the established functional imaging tests for the presurgical evaluation of epileptic onset zone in patients with intractable partial epilepsy. In temporal lobe epilepsy the sensitivity of these methods was shown to be excellent, in particular if a multimodal platform is used, which combines the functional imaging with the additional morphological information of magnetic resonance imaging (MRI), but was lower in extra temporal lobe epilepsy. Functional imaging with SPECT and PET reflects seizure related changes of cerebral perfusion, glucose-metabolism and neuroreceptor status. In this review the usefulness of SPECT and PET imaging in clinical routine in epilepsy as well as the role of different neuroreceptor PET-tracer, which were used in epilepsy are discussed. The use of perfusion SPECT tracer allows the investigation of ictal activations, but the low temporal resolution of ictal perfusion SPECT often results in the detection of both the ictal onset zone as well as the propagation pathways, an area that has not always need to be resected in order to render a patient seizure free. The additional use of interictal PET with fluorine-18 fluorodeoxyglucose which measures regional cerebral metabolism or interictal perfusion SPECT enhance the informational value of ictal SPECT and were shown to be important tools to better define the ictal onset and surround inhibition zones. In recent years PET imaging of different cerebral neuroreceptor-systems inter alia GABA(A) receptors, serotonin receptors (5-HT(1A)), opioid receptors as well as dopamine receptors was used to investigate the neurochemical basis of epilepsy, the role of these neurotransmitters for the epileptogenesis as well as the spread of epileptic activity during seizures and partially entered in clinical routine. Currently some of these radioligands are also used to investigate new treatment approaches.

[Reduced bone density and bone pain :osteomalacia with hypophospatemia and hypophosphaturia]. / Erniedrigte Knochendichte und Knochenschmerzen : Osteomalazie mit Hypophosphatämie und Hyperphosphaturie.

Two patients aged 24 and 64 years presented at our hospital with similar symptoms including bone pain and muscle weakness. Basic laboratory tests and urinary diagnostics, bone densitometry and bone histology revealed severe osteomalacia with renal phosphate wasting. After the exclusion of other causes an extensive tumor search was performed due to suspected tumor-induced osteomalacia. In one patient a mesenchymal tumor was found in the thigh and completely resected. After surgery the patient showed a rapid recovery from osteomalacia. Because the search was unsuccessful in the other patient phosphorus supplementation in combination with calcitriol was started. Despite continuing renal phosphate wasting a significant increase in bone mineral density was observed.

Anti-Ma and anti-Ta associated paraneoplastic neurological syndromes: 22 newly diagnosed patients and review of previous cases.

BACKGROUND: Paraneoplastic neurological syndromes (PNS) are indirect remote effects of cancer on the nervous system, often associated with the presence of specific serum antibodies. The most recently described PNS defining reactivity is anti-Ma/anti-Ta. Here we present 22 newly diagnosed patients with anti-Ma or anti-Ta reactivity, refine the associated clinical picture and review all published patients to date. PATIENTS AND METHODS: Patients were identified by testing for PNMA1 and PNMA2 antibodies by western blotting and indirect immunofluorescence. Clinical data were obtained either by referral of the patient or from the referring physicians. RESULTS: Analysis of 22 new patients (14 anti-Ma, eight anti-Ta) confirmed that anti-Ta are usually found in young men with limbic encephalitis and testicular germ cell tumours who stabilise neurologically with long term survival after tumour treatment. Patients with anti-Ma were of either sex, middle-aged, presented with a range of tumours and neurological symptoms and had a limited response to treatment. Furthermore, we expanded the range of associated clinical features: (1) the peripheral nervous system may be involved; (2) an overlap with anti-Hu is possible; and (3) testicular tumour manifestation can be extragonadal or detectable only at orchiectomy. CONCLUSION: Refining and expanding the range of anti-Ma/anti-Ta associated neurological presentations and tumours clearly demonstrated that the distinction between anti-Ma and anti-Ta associated PNS is of high clinical relevance.

Dual-isotope SPECT imaging of striatal dopamine: first episode, drug naïve schizophrenic patients.

OBJECTIVE: The aim of this investigation was to evaluate the usefulness of a dual-isotope SPECT technique to assess simultaneously striatal dopamine binding structures - presynaptic dopamine transporter (DAT) and postsynaptic dopamine D(2) receptor - in first-episode, drug-naive schizophrenic patients compared to healthy control persons. Additionally, relations between radioligand binding to DAT and D(2) and positive symptoms were assessed. METHODS: Twenty acutely ill inpatients suffering from a first acute schizophrenic episode and 12 healthy control persons participated in the study. Patients were naïve with respect to neuroleptic or antidepressant medication. A dual-isotope SPECT protocol was performed using combined application of [99mTc]TRODAT-1 and [123I]IBZM. On the day of SPECT, psychopathology was assessed in the patient group by PANSS rating. RESULTS: In the patient but not in the healthy control group there was a significant correlation between DAT and D(2) receptor availability. Patients with predominant positive symptoms (n=12) had a significantly higher DAT availability compared to the healthy control group. An inverse correlation between DAT and D(2) availability and the extent of "delusions", "conceptual disorganization", and "hallucinatory behaviour" could be demonstrated. DISCUSSION: The data obtained with this dual-isotope SPECT technique show a change in interaction between striatal DAT and D(2) receptor in first-episode, never-treated schizophrenic patients. Additionally, an association between dopamine transmission and the core symptoms of the acute psychotic syndrome was found.

Restaging of patients with lymphoma. Comparison of low dose CT (20 mAs) with contrast enhanced diagnostic CT in combined [18F]-FDG PET/CT.

AIM: Assessment of the clinical benefit of i.v. contrast enhanced diagnostic CT (CE-CT) compared to low dose CT with 20 mAs (LD-CT) without contrast medium in combined [(18)F]-FDG PET/CT examinations in restaging of patients with lymphoma. PATIENTS, METHODS: 45 patients with non-Hodgkin lymphoma (n=35) and Hodgkin's disease (n=10) were included into this study. PET, LD-CT and CE-CT were analyzed separately as well as side-by-side. Lymphoma involvement was evaluated separately for seven regions. Indeterminate diagnoses were accepted whenever there was a discrepancy between PET and CT findings. Results for combined reading were calculated by rating indeterminate diagnoses according the suggestions of either CT or PET. Each patient had a clinical follow-up evaluation for >6 months. RESULTS: Region-based evaluation suggested a sensitivity/specificity of 66/93% for LD-CT, 87%/91% for CE-CT, 95%/96% for PET, 94%/99% for PET/LD-CT and 96%/99% for PET/CE-CT. The data for PET/CT were obtained by rating indeterminate results according to the suggestions of PET, which turned out to be superior to CT. Lymphoma staging was changed in two patients using PET/CE-CT as compared to PET/LD-CT. CONCLUSION: Overall, there was no significant difference between PET/LD-CT and PET/CE-CT. However, PET/CE-CT yielded a more precise lesion delineation than PET/LD-CT. This was due to the improved image quality of CE-CT and might lead to a more accurate investigation of lymphoma.

Combined PET/MRI: Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tübingen, Germany.

The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tübingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.