[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.

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.

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.

Assessment of the parenchymal blood volume by C-arm computed tomography for radioembolization dosimetry.

PURPOSE: Aim of the study was to evaluate the impact of parenchymal blood volume (PBV) C-arm CT in transarterial radioembolization (TARE) planning procedure regarding the appropriateness of segmental blood supply from selective catheter positions defined by angiographic images compared to PBV mapsto determine the influence of changed target volumes on dose calculation. MATERIAL AND METHODS: A total of 22 consecutive patients (median age, 62 years) underwent a TARE planning procedure were included in this retrospective study. Selective angiograms and selective PBV C-arm CT (right and left liver lobe) were evaluated in a blinded fashion, regarding segmental hepatic artery variants. Volumetry of target volume and dosimetry of glass and resin microspheres were performed. RESULTS: Classification of segment IV and segment I to the corresponding target vascular bed supply was correct in 91.0% (20/22) and 86.4% (19/22) for angiography and C-arm CT, respectively. Except one case, all other liver segments were classified properly to the left and right hepatic arterial supply. Based on the mismatch of the angiographic and the C-arm CT approach, changes of target volume were evident in 27.3% of patients, resulting in a mean mismatch volume of 90±54ml (range, 51-198ml) and a percentage of dose differences of 14.2±11.8% and 12.6±10.6% for the right and 12.5±8.5% and 11.1±7.8% for the left liver lobe in glass and resin microspheres, respectively. CONCLUSION: The C-arm CT approach is superior to the angiographic determination of vascular supply of specific liver segments for dosimetry before radioembolization. Especially for unexperienced interventional radiologists or for a complex anatomy, C-arm CT improves individualized dosimetry concepts.

Combined PET/MRI: from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tübingen, Germany.

This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tübingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.

[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.

[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.

Pediatric Oncologic Imaging: A Key Application of Combined PET/MRI.

UNLABELLED: Pediatric imaging has been identified as a key application of combined whole-body PET/MRI. First studies have revealed the clinical feasibility and possible advantages of PET/MRI over PET/CT and MRI. Besides a significant reduction in radiation exposure of about 50 - 75 %, combined whole-body PET/MRI offers the diagnostic advantage of the multiparametric characterization of pathophysiologic processes and helps reduce the number of necessary imaging studies. However, very few studies focusing on pediatric PET/MRI have been published to date. Additional studies are necessary in order to fully appreciate the clinical impact of this novel method. This review article shall summarize the existing literature concerning pediatric PET/MRI and give insight into the practical experience derived from over 160 pediatric PET/MRI examinations that were performed in Tübingen. KEY POINTS: •Combined PET/MR is a promising imaging modality in pediatric oncology. •Using combined PET/MRI, diagnostic radiation exposure of pediatric patients and the number of necessary imaging studies can be reduced. •Further clinical studies are necessary in order to define specific indications for combined PET/MRI in pediatric radiology.

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.

Combined PET/MRI: Multi-modality Multi-parametric Imaging Is Here: Summary Report of the 4th International Workshop on PET/MR Imaging; February 23-27, 2015, Tübingen, Germany.

This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology, neurology and multi-parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both technical versatility and acceptance by clinical and research-driven users from the status quo of last year. Still, with only minimal evidence of progress made in exploiting the true complementary nature of the PET and MRI-based information, PET/MRI is still yet to achieve its potential. In that regard, the conclusion of last year's meeting "the real work has just started" still holds true.

Hybrid MR-PET in Neuroimaging.

Hybrid magnetic resonance (MR)-positron emission tomography (MR-PET) is a novel technology with advantages over sequential MR and PET imaging, allowing maintain full individual diagnostic performance with negligible mutual interference between the two hardware settings. Obvious synergies between MR and PET in acquisition of anatomical, functional, and molecular information for neurological diseases into one single image pave the way for establishing clear clinical indications for hybrid MR-PET as well as addressing unmet neuroimaging needs in future clinics and research. Further developments in attenuation correction, quantification, workflow, and effective MR-PET data management might unfold the full potential of integrated multimodality imaging.

Combined PET/MR: The Real Work Has Just Started. Summary Report of the Third International Workshop on PET/MR Imaging; February 17-21, 2014, Tübingen, Germany.

This paper summarises the proceedings and discussions at the third annual workshop held in Tübingen, Germany, dedicated to the advancement of the technical, scientific and clinical applications of combined PET/MRI systems in humans. Two days of basic scientific and technical instructions with "hands-on" tutorials were followed by 3 days of invited presentations from active researchers in this and associated fields augmented by round-table discussions and dialogue boards with specific themes. These included the use of PET/MRI in paediatric oncology and in adult neurology, oncology and cardiology, the development of multi-parametric analyses, and efforts to standardise PET/MRI examinations to allow pooling of data for evaluating the technology. A poll taken on the final day demonstrated that over 50 % of those present felt that while PET/MRI technology underwent an inevitable slump after its much-anticipated initial launch, it was now entering a period of slow, progressive development, with new key applications emerging. In particular, researchers are focusing on exploiting the complementary nature of the physiological (PET) and biochemical (MRI/MRS) data within the morphological framework (MRI) that these devices can provide. Much of the discussion was summed up on the final day when one speaker commented on the state of PET/MRI: "the real work has just started".

[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.

Hot spots in dynamic (18)FET-PET delineate malignant tumor parts within suspected WHO grade II gliomas.

Molecular imaging studies have recently found inter- and intratumoral heterogeneity in World Health Organization (WHO) grade II gliomas. A correlative analysis with tumor histology, however, is still lacking. For elucidation we conducted the current prospective study. Fifty-five adult patients with an MRI-based suspicion of a WHO grade II glioma were included. [F-18]Fluoroethyltyrosine ((18)FET) uptake kinetic studies were combined with frame-based stereotactic localization techniques and used as a guide for stepwise (1-mm steps) histopathological evaluation throughout the tumor space. In tumors with heterogeneous PET findings, the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and expression of mutated protein isocitrate dehydrogenase variant R132H (IDH1) were determined inside and outside of hot spot volumes. Metabolic imaging revealed 3 subgroups: the homogeneous WHO grade II glioma group (30 patients), the homogeneous malignant glioma group (10 patients), and the heterogeneous group exhibiting both low- and high-grade characteristics at different sites (15 patients). Stepwise evaluation of 373 biopsy samples indicated a strong correlation with analyses of uptake kinetics (p < 0.0001). A homogeneous pattern of uptake kinetics was linked to homogeneous histopathological findings, whereas a heterogeneous pattern was associated with histopathological heterogeneity; hot spots exhibiting malignant glioma characteristics covered 4-44% of the entire tumor volumes. Both MGMT and IDH1 status were identical at different tumor sites and not influenced by heterogeneity. Maps of (18)FET uptake kinetics strongly correlated with histopathology in suspected grade II gliomas. Anaplastic foci can be accurately identified, and this finding has implications for prognostic evaluation and treatment planning.

[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.

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.