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Purpose: Small molecule drug conjugates (SMDC) are modular anticancer prodrugs that include a tumor-targeting small organic ligand, a cleavable linker, and a potent cytotoxic agent. Most of the SMDC products that have been developed for clinical applications target internalizing tumor-associated antigens on the surface of tumor cells. We have recently described a novel non-internalizing small organic ligand (named OncoFAP) of fibroblast activation protein (FAP), a tumor-associated antigen highly expressed in the stroma of most solid human malignancies. Experimental Design: In this article, we describe a new series of OncoFAP-Drug derivatives based on monomethyl auristatin E (MMAE; a potent cytotoxic tubulin poison) and dipeptide linkers that are selectively cleaved by FAP in the tumor microenvironment. Results: The tumor-targeting potential of OncoFAP was confirmed in patients with cancer using nuclear medicine procedures. We used mass spectrometry methodologies to quantify the amount of prodrug delivered to tumors and normal organs, as well as the efficiency of the drug release process. Linkers previously exploited for anticancer drug conjugates were used as benchmark. We identified OncoFAP-Gly-Pro-MMAE as the best performing SMDC, which has now been prioritized for further clinical development. OncoFAP-Gly-Pro-MMAE selectively delivered more than 10% injected dose per gram of MMAE to FAP-positive tumors, with a tumor-to-kidney ratio of 16:1 at 24 hours post-injection. Conclusions: The FAP-specific drug conjugates described in this article promise to be efficacious for the targeting of human malignancies. The extracellular release of potent anticancer payloads mediates durable complete remission in difficult-to-treat animal models of cancer.

(18)F-FDG PET/MRI might be the diagnostic method of choice for Hodgkin lymphoma patients, as it combines significant metabolic information from PET with excellent soft-tissue contrast from MRI and avoids radiation exposure from CT. However, a major issue is longer examination times than for PET/CT, especially for younger children needing anesthesia. Thus, a targeted selection of suitable whole-body MRI sequences is important to optimize the PET/MRI workflow. Methods: The initial PET/MRI scans of 84 EuroNet-PHL-C2 study patients from 13 international PET centers were evaluated. In each available MRI sequence, 5 PET-positive lymph nodes were assessed. If extranodal involvement occurred, 2 splenic lesions, 2 skeletal lesions, and 2 lung lesions were also assessed. A detection rate was calculated dividing the number of visible, anatomically assignable, and measurable lesions in the respective MRI sequence by the total number of lesions. Results: Relaxation time–weighted (T2w) transverse sequences with fat saturation (fs) yielded the best result, with detection rates of 95% for nodal lesions, 62% for splenic lesions, 94% for skeletal lesions, and 83% for lung lesions, followed by T2w transverse sequences without fs (86%, 49%, 16%, and 59%, respectively) and longitudinal relaxation time–weighted contrast-enhanced transverse sequences with fs (74%, 35%, 57%, and 55%, respectively). Conclusion: T2w transverse sequences with fs yielded the highest detection rates and are well suited for accurate whole-body PET/MRI in lymphoma patients. There is no evidence to recommend the use of contrast agents.

Purpose:Small molecule drug conjugates (SMDC) are modular anticancer prodrugs that include a tumor-targeting small organic ligand, a cleavable linker, and a potent cytotoxic agent. Most of the SMDC products that have been developed for clinical applications target internalizing tumor-associated antigens on the surface of tumor cells. We have recently described a novel non-internalizing small organic ligand (named OncoFAP) of fibroblast activation protein (FAP), a tumor-associated antigen highly expressed in the stroma of most solid human malignancies.Experimental Design:In this article, we describe a new series of OncoFAP-Drug derivatives based on monomethyl auristatin E (MMAE; a potent cytotoxic tubulin poison) and dipeptide linkers that are selectively cleaved by FAP in the tumor microenvironment.Results:The tumor-targeting potential of OncoFAP was confirmed in patients with cancer using nuclear medicine procedures. We used mass spectrometry methodologies to quantify the amount of prodrug delivered to tumors and normal organs, as well as the efficiency of the drug release process. Linkers previously exploited for anticancer drug conjugates were used as benchmark. We identified OncoFAP-Gly-Pro-MMAE as the best performing SMDC, which has now been prioritized for further clinical development. OncoFAP-Gly-Pro-MMAE selectively delivered more than 10% injected dose per gram of MMAE to FAP-positive tumors, with a tumor-to-kidney ratio of 16:1 at 24 hours post-injection.Conclusions:The FAP-specific drug conjugates described in this article promise to be efficacious for the targeting of human malignancies. The extracellular release of potent anticancer payloads mediates durable complete remission in difficult-to-treat animal models of cancer.

Supplementary Information

Radioembolization is the selective application of radionuclide-loaded microspheres into liver arteries for the therapy of liver tumours and metastases. In this review, we focused on therapy planning and dosimetry, as well as the main indications of 90Y-glass and resin microspheres and 166Ho-microspheres.Radioembolisation ist die selektive Applikation Radionuklid-beladener Mikrosphären in Leberarterien zur Therapie von Lebertumoren und -metastasen. In diesem Review konzentrierten wir uns auf die Therapieplanung und Dosimetrie sowie auf die Hauptindikationen von 90Y-Glas- und Harz-Mikrosphären und 166Ho-Mikrosphären.

Objective The objective of this study was to assess the accuracy of 68Ga-PSMA-11 PET/MRI, 18F-PSMA-1007 PET/CT, 68Ga-PSMA-11 PET/CT, and multiparametric (mp)MRI for the delineating of dominant intraprostatic lesions (IPL). Materials and methods 35 patients with organ-confined prostate cancer who were assigned to definitive radiotherapy (RT) were divided into three groups based on imaging techniques: 68Ga-PSMA-PET/MRI (n = 9), 18F-PSMA-PET/CT (n = 16) and 68Ga-PSMA-PET/CT (n = 10). All patients without PSMA-PET/MRI received an additional mpMRI. PSMA-PET-based automatic isocontours and manual contours of the dominant IPLs were generated for each modality. The biopsy results were then used to validate whether any of the prostate biopsies were positive in the marked lesion using Dice similarity coefficient (DSC), Youden index (YI), sensitivity and specificity. Factors that can predict the accuracy of IPLs contouring were analysed. Results Diagnostic performance was significantly superior both for manual and automatic IPLs contouring using 68Ga-PSMA-PET/MRI (DSC/YI SUV70%—0.62/0.51), 18F-PSMA-PET/CT (DSC/YI SUV70%—0.67/0.53) or 68Ga-PSMA-PET/CT (DSC/YI SUV70%—0.63/0.51) compared to mpMRI (DSC/YI—0.47/0.41; p Conclusion IPL localization was significantly improved when using PSMA-imaging procedures compared to mpMRI. No significant difference for delineating IPLs was found between hybrid method PSMA-PET/MRI and PSMA-PET/CT. PSMA-based imaging technique should be considered for the diagnostics of IPLs and focal treatment modality.

Objective Surgical resection is the therapy of choice in head and neck paraganglioma but is associated with considerable morbidity. For treatment of inoperable or progressive disease, less aggressive adjuvant options are warranted. This study assessed effectiveness and safety of peptide receptor radionuclide therapy (PRRT) with lutetium-177–DOTATATE for head and neck paraganglioma with emphasis on response assessment. Methods A retrospective analysis of 7 patients with head and neck paraganglioma treated with PPRT between May 2014 and October 2016 was performed. Three patients had jugulotympanic paraganglioma, 3 patients had carotid body tumors, and 1 patient had a combination of both. Patients underwent PRRT after discussion in the local tumor board regarding progressive disease, inoperability, or lack of other adjuvant options. All patients underwent 3–5 cycles of PRRT. Treatment response was evaluated by gallium-68–DOTATATE positron emission tomography/computed tomography and contrast-enhanced computed tomography or magnetic resonance imaging. Outcome measures were two-dimensional tumor diameters and total tumor volumes. Results Median patient age was 60 years (interquartile range: 14–84 years). All patients had stable disease at posttherapy assessment. Decreasing tumor volumes were found in 4 patients. Clinical symptoms improved in 2 patients. No progression or adverse events occurred during a median follow-up of 39 months (interquartile range: 35–47 months). Conclusions Somatostatin receptor–targeted therapy using lutetium-177-DOTATATE shows promising effectiveness with a high safety profile. Patients in whom surgical morbidity outweighs oncologic benefit should be informed about PRRT as a treatment option.

Neuroendokrine Tumoren (NET) entstehen aus dem Neuroektoderm und konnen in den verschiedensten Organen des Korpers lokalisiert werden. Am haufigsten ist ihr Auftreten im gastroenteropankreatischen System. Die Heterogenitat dieser Tumorentitat sowie die zahlreichen Lokal- bzw. Systemtherapien fuhren zu einer Vielzahl von unterschiedlichen Behandlungsoptionen. Auch die Ziele einer Therapie konnen unterschiedlich sein: Sie reichen von einem kurativen Ansatz uber Kontrolle des Tumorwachstums und dem Verhindern von lokalen obstruktiven Beschwerden (z. B. bei Dunndarm-NETs) bis hin zur Kontrolle von durch vermehrte Sekretion von Peptidhormonen/-aminen ausgelosten Symptomen. Diese Ubersichtsarbeit stellt die wichtigsten Neuerungen in der Klassifikation der neuroendokrinen Neoplasien vor, insbesondere die Unterscheidung von NET-G3-Tumoren und neuroendokrinen Karzinomen (NEC). Vorgestellt werden die Optionen einer operativen Therapie, welche immer zuerst gepruft werden sollte, lokal ablativer Verfahren, die vor allem Anwendung bei kleinen (

Respiratory gating is the standard to prevent respiration effects from degrading image quality in PET. Data-driven gating (DDG) using signals derived from PET raw data is a promising alternative to gating approaches requiring additional hardware (e.g., pressure-sensitive belt gating [BG]). However, continuous-bed-motion (CBM) scans require dedicated DDG approaches for axially extended PET, compared with DDG for conventional step-and-shoot scans. In this study, a CBM-capable DDG algorithm was investigated in a clinical cohort and compared with BG using optimally gated (OG) and fully motion-corrected (elastic motion correction [EMOCO]) reconstructions. Methods: Fifty-six patients with suspected malignancies in the thorax or abdomen underwent whole-body 18F-FDG CBM PET/CT using DDG and BG. Correlation analyses were performed on both gating signals. Besides static reconstructions, OG and EMOCO reconstructions were used for BG and DDG. The metabolic volume, SUVmax, and SUVmean of lesions were compared among the reconstructions. Additionally, the quality of lesion delineation in the different PET reconstructions was independently evaluated by 3 experts. Results: The global correlation coefficient between BG and DDG signals was 0.48 ± 0.11, peaking at 0.89 ± 0.07 when scanning the kidney and liver region. In total, 196 lesions were analyzed. SUV measurements were significantly higher in BG-OG, DDG-OG, BG-EMOCO, and DDG-EMOCO than in static images (P < 0.001; median SUVmax: static, 14.3 ± 13.4; BG-EMOCO, 19.8 ± 15.7; DDG-EMOCO, 20.5 ± 15.6; BG-OG, 19.6 ± 17.1; and DDG-OG, 18.9 ± 16.6). No significant differences between BG-OG and DDG-OG or between BG-EMOCO and DDG-EMOCO were found. Visual lesion delineation was significantly better in BG-EMOCO and DDG-EMOCO than in static reconstructions (P < 0.001); no significant difference was found when comparing BG and DDG for either EMOCO or OG reconstruction. Conclusion: DDG-based motion compensation of CBM PET acquisitions outperforms static reconstructions, delivering qualities comparable to BG approaches. The new algorithm may be a valuable alternative for CBM PET systems.

177Lutetium PSMA-617 (Lu-PSMA) therapy in patients with metastatic castration resistant prostate cancer (mCRPC) has gained visibility through the ongoing phase III trial. The data on prediction of therapy outcome and survival out of pretherapeutic imaging parameters is still sparse. In this study, the predictive and prognostic value of radiomic features from 68Ga-PSMA-11 PET-MRI are analyzed. In total, 21 patients with mCRPC underwent 68Ga-PSMA-11 PET-MRI before Lu-PSMA therapy. The PET-positive tumor volume was defined and transferred to whole-body T2-, T1- and contrast-enhanced T1-weighted MRI-sequences. The radiomic features from PET and MRI sequences were extracted by using a freely available software package. For selecting features that allow differentiation of biochemical response (PSA decrease &gt, 50%), a stepwise dimension reduction was performed. Logistic regression models were fitted, and selected features were tested for their prognostic value (overall survival) in all patients. Eight patients achieved biochemical response after Lu-PSMA therapy. Ten independent radiomic features differentiated well between responders and non-responders. The logistic regression model, including the feature interquartile range from T2-weighted images, revealed the highest accuracy (AUC = 0.83) for the prediction of biochemical response after Lu-PSMA therapy. Within the final model, patients with a biochemical response (p = 0.003) and higher T2 interquartile range values in pre-therapeutic imaging (p = 0.038) survived significantly longer. This proof-of-concept study provides first evidence on a potential predictive and prognostic value of radiomic analysis of pretherapeutic 68Ga-PSMA-11 PET-MRI before Lu-PSMA therapy.

Simple Summary PSMA Therapy has recently become an additional therapeutic option in advanced prostate cancer. In the present study, the predictive and prognostic value of radiomic features from pretherapeutic PSMA PET-MRI are analyzed. Twenty-one patients with advanced prostate cancer underwent PSMA-therapy, including pretherapeutic PSMA PET-MRI. Radiomic features from PET- and MRI-sequences were extracted and processed to select the features differentiating responders and non-responders. Out of ten independent radiomic features differentiating between these two groups, the feature interquartile range from the T2 weighted images revealed the highest accuracy. PSA response and higher T2 interquartile range values might have impact on survival. This proof-of-concept study applies radiomic analysis to pretherapeutic PSMA PET-MRI before PSMA therapy, providing new parameters with potential predictive and prognostic value. Abstract 177Lutetium PSMA-617 (Lu-PSMA) therapy in patients with metastatic castration resistant prostate cancer (mCRPC) has gained visibility through the ongoing phase III trial. The data on prediction of therapy outcome and survival out of pretherapeutic imaging parameters is still sparse. In this study, the predictive and prognostic value of radiomic features from 68Ga-PSMA-11 PET-MRI are analyzed. In total, 21 patients with mCRPC underwent 68Ga-PSMA-11 PET-MRI before Lu-PSMA therapy. The PET-positive tumor volume was defined and transferred to whole-body T2-, T1- and contrast-enhanced T1-weighted MRI-sequences. The radiomic features from PET and MRI sequences were extracted by using a freely available software package. For selecting features that allow differentiation of biochemical response (PSA decrease > 50%), a stepwise dimension reduction was performed. Logistic regression models were fitted, and selected features were tested for their prognostic value (overall survival) in all patients. Eight patients achieved biochemical response after Lu-PSMA therapy. Ten independent radiomic features differentiated well between responders and non-responders. The logistic regression model, including the feature interquartile range from T2-weighted images, revealed the highest accuracy (AUC = 0.83) for the prediction of biochemical response after Lu-PSMA therapy. Within the final model, patients with a biochemical response (p = 0.003) and higher T2 interquartile range values in pre-therapeutic imaging (p = 0.038) survived significantly longer. This proof-of-concept study provides first evidence on a potential predictive and prognostic value of radiomic analysis of pretherapeutic 68Ga-PSMA-11 PET-MRI before Lu-PSMA therapy.

Background: High protein (HP) diets have been proposed to reduce body weight in humans. The diets are known to alter energy metabolism, which can affect the quality of [18F]FDG PET heart images. In this preclinical study, we therefore explore the impact of a prolonged HP diet on myocardial [18F]FDG uptake. Methods: C57BL/6J (Black six (Bl6)) and apolipoprotein E-deficient (apoE−/−) mice were fed chow, a HP diet, or a low protein (LP) diet for 12 weeks. At baseline and after treatment, the animals were injected with 33.0 MBq of [18F]FDG and a 30 min PET/CT scan was made. Myocardial volume and [18F]FDG uptake were quantified using PET and the % of body fat was calculated from CT. Results: Myocardial [18F]FDG uptake was similar for all diets at the follow-up scan but an increase between baseline and follow-up scans was noticed in the LP groups. Myocardial volume was significantly smaller in the C57BL HP group compared to the other Bl6 groups. Body weight increased less in the two HP groups compared to the chow and LP groups. Body fat percentage was significantly higher in the LP groups. This effect was stronger in C57BL mice (28.7%) compared to apoE−/− mice (15.1%). Conclusions: Myocardial uptake of [18F]FDG in mice is not affected by increased protein intake but [18F]FDG uptake increases when the amount of protein is lowered. A lower body weight and percentage of body fat were noticed when applying a HP diet.

Background While the prognosis of patients with Ewing sarcoma (EwS) is improving, little is known about the frequency of pain and its risk factors in survivors of EwS. This study aims to analyse the prevalence and risk factors of pain and its predictive value for recurrence. Patients and methods In patients with remission after treatment of EwS, frequency and characteristics of pain within the first 5 years of follow up were assessed retrospectively. Results Of 80 patients, 37 (46%) presented with at least one episode of pain. Chronic pain (>3 months) was observed in 10 patients (13%). Experience of at least one episode of pain was associated with prior combined local treatment (surgery and radiation compared to surgery alone; odds ratio [OR] 5.83, 95% confidence interval [CI] 1.43-34.9, P = .007). A total of 59 episodes of pain were observed, including 47 acute and 12 chronic episodes. Lower limb pain accounted for 46% (27/59) of all episodes of pain, and was associated with primary tumour of the pelvis or lower extremity (OR 4.29, 95% CI 1.18-18.21, P = .025), which represented 64% (51/80) of all EwS. The positive predictive value of pain for recurrence was only 12%. Conclusion Pain is a common problem in survivors of EwS, which mostly affects the lower extremity, and should be regularly assessed. Interventions to reduce pain may be particularly important in patients with combined local treatment with surgery and radiation, who seem to be at considerably increased risk for pain. Patients presenting with pain should be examined for recurrence.

Background In somatostatin receptor (SSTR) expressing progressive meningioma, peptide receptor radionuclide therapy (PRRT) has shown effect in small clinical series. However, standardized treatment and response assessment protocols are lacking. We present our experience on PPRT with 177Lu-DOTATATE in progressive meningioma with a special emphasis on state-of-the-art response assessment. Methods Retrospective analysis on PRRT with 177Lu-DOTATATE from 2015 to 2019. Pre- and post-therapy imaging was performed using MRI and 68Ga-DOTATATE-PET for standard bidimensional and volumetric analyses, respectively, following novel RANO guidelines. Results Seven patients with progressive intracranial meningioma (median age 73 years, interquartile range 60–76; 5 WHO II, 2 WHO I; 5 multifocal) received a median of 4 cycles 2 3 4 of PRRT with 177Lu-DOTATATE in eight-week intervals. Three patients did not undergo post-therapy 68Ga-DOTATATE-PET due to early symptomatic progression and subsequent cessation of PRRT. After completion of 4 PRRT cycles volumetric PET imaging showed stable disease in two of four patients. According to bidimensional MRI response assessment, only one patient was stable. Progression free survival at six months was 42.9 %. Conclusion In this heterogeneous collective of seven patients with progressive meningioma, 177Lu-DOTATATE therapies showed heterogeneous effectiveness. PET-based volumetric assessment should be used for response assessment in PRRT additionally to bidimensional imaging.

Purpose To analyze patients’ characteristics and reasons for not performing planned transarterial radioembolization (TARE) in liver cancer after 99mTc-labeled macroaggregated albumin (99mTc-MAA) evaluation. Methods In this retrospective single-center cohort, all patients undergoing 99mTc-MAA evaluation prior to planned TARE for primary or secondary liver cancer between 2009 and 2018 were analyzed. Patients were assigned to either “TARE” or “no TARE” group. Patients’ characteristics, arising reasons for not performing the planned TARE treatment as well as predictive factors for occurrence of these causes were analyzed. Results 436 patients [male = 248, female = 188, median age 62 (23–88) years] with 99mTc-MAA evaluation prior to planned TARE of primary or secondary liver cancer were included in this study. 148 patients (33.9%) did not receive planned TARE. Patients with a hepatic tumor burden > 50%, no liver cirrhosis, no previous therapies and a higher bilirubin were significantly more frequent in “no TARE” compared to “TARE” group. Main reasons for not performing TARE were extrahepatic tracer accumulation (n = 70, 40.5%), non-target accumulation of 99mTc-MAA (n = 27, 15.6%) or a hepatopulmonary shunt fraction of more than 20% (n = 23, 13.3%). Independent preprocedural parameters for not performing planned TARE were elevated bilirubin (p = 0.021) and creatinine (p = 0.018) and lower MELD score (p = 0.031). Conclusion A substantial number of patients are precluded from TARE following 99mTc-MAA evaluation, which is, therefore, implicitly needed to determine contraindications to TARE and should not be refrained from in pretreatment process. However, a preceding careful patient selection is needed especially in patients with high hepatic tumor burden and alteration in lab parameters.

Metastatic colorectal cancer (mCRC) is associated with different molecular biology, clinical characteristics, and outcome depending on the primary tumor localization. We aimed to evaluate the effectiveness of 90Y-radioembolization (RE) for therapy of colorectal liver metastases depending on the primary tumor side.We performed a retrospective analysis of n = 73 patients with mCRC and RE in our university liver center between 2009 and 2018. Patients were stratified according to the primary tumor side (left vs. right hemicolon), treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) at follow-up after 3 months. Kaplan-Meier analysis was performed to analyze survival followed by Cox regression to determine independent prognostic factors for survival.Prior to RE, all patients had received systemic therapy, with either stable or progressive disease, but no partial or complete response. In n = 22/73 (30.1%) patients, the primary tumor side was in the right colon; in n = 51/73 (69.9%) patients, in the left colon. Hepatic tumor burden was ≤25% in n = 36/73 (49.3%) patients and25% in n = 37/73 (50.7%) patients. At 3 months, n = 21 (33.8%) patients showed treatment response (n = 2 [3.2%]; complete response, n = 19 [30.6%]; partial response), n = 13 (21.0%) stable disease, and n = 28 (45.2%) progressive disease after RE. The median survival in case of primary tumor side in the left colon was significantly higher than for primary tumors in the right colon (8.7 vs. 6.0 months, p = 0.033). The median survival for a hepatic tumor burden ≤25% was significantly higher than that of25% (13.9 vs. 4.3 months, p0.001). The median overall survival was 6.1 months.The median survival after RE in hepatic-mCRC depends on the primary tumor side and the preprocedural hepatic tumor burden.

Purpose: To evaluate factors associated with survival following transarterial 90Y (yttrium) radioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC). Methods: This retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in patients with advanced ICC following resin microsphere TARE. Patients were included either after failed previous anticancer therapy, including relapse after surgical resection, or for having a minimum of 25% of total liver volume affected by ICC. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan&ndash, Meier analysis was performed to analyze survival followed by cox regression to determine independent prognostic factors for survival. Results: 46 patients were included (19 male, 27 female), median age 62.5 years (range 29&ndash, 88 years). A total of 65% of patients had undergone previous therapy, while 63% had a tumor volume &gt, 25% of the entire liver volume. Median survival was 9.5 months (95% CI: 6.1&ndash, 12.9 months). Due to loss in follow-up, n = 37 patients were included in the survival analysis. Cox regression revealed the extent of liver disease to one or both liver lobes being associated with survival, irrespective of tumor volume (p = 0.041). Patients with previous surgical resection of ICC had significantly decreased survival (3.9 vs. 12.8 months, p = 0.002). No case of radiation-induced liver disease was observed. Discussion: Survival after 90Y TARE in patients with advanced ICC primarily depends on disease extent. Only limited prognostic factors are associated with a general poor overall survival.

Background We aimed to compare the prognostic value of myocardial perfusion scintigraphy (MPS) and dobutamine stress echocardiography (DSE) in patients with end-stage renal disease (ESRD) without known coronary artery disease. Methods Two-hundred twenty-nine ESRD patients who applied for kidney transplantation at our centre were prospectively evaluated by MPS and DSE. The primary endpoint was a composite of myocardial infarction (MI) or all-cause mortality. The secondary endpoint included MI or coronary revascularization (CR) not triggered by MPS or DSE at baseline. Results MPS detected reversible ischemia in 31 patients (13.5%) and fixed perfusion defects in 13 (5.7%) patients. DSE discovered stress-induced wall motion abnormalities (WMAs) in 28 (12.2%) and at rest in 18 (7.9%) patients. MPS and DSE results agreed in 85.6% regarding reversible defects (κ = 0.358; P < .001) and in 90.8% regarding fixed defects (κ = 0.275; P < .001). Coronary angiography detected relevant stenosis > 50% in only 15 of 38 patients (39.5%) with pathological findings in MPS and/or DSE. At a median follow-up of 8 years and 10 months, the primary endpoint occurred in 70 patients (30.6%) and the secondary endpoint in 24 patients (10.5%). The adjusted Cox hazard ratios (HRs) for the primary endpoint were 1.77 (95% CI 1.02-3.08; P = .043) for perfusion defects in MPS and 1.36 (95% CI 0.78-2.37; P = ns) for WMA in DSE. The secondary endpoint was significantly correlated with the findings of both modalities, MPS (HR 3.21; 95% CI 1.35-7.61; P = .008) and DSE (HR 2.67; 95% CI 1.15-6.20; P = .022). Conclusion Perfusion defects in MPS are a stronger determinant of all-cause mortality, MI and the need for future CR compared with WMAs in DSE. Given the complementary functional information provided by MPS vs DSE, results are sometimes contradictory, which may indicate differences in the underlying pathophysiology.

Purpose Data‐driven gating (DDG) approaches for positron emission tomography (PET) are interesting alternatives to conventional hardware‐based gating methods. In DDG, the measured PET data themselves are utilized to calculate a respiratory signal, that is, subsequently used for gating purposes. The success of gating is then highly dependent on the statistical quality of the PET data. In this study, we investigate how this quality determines signal noise and thus motion resolution in clinical PET scans using a center‐of‐mass‐based (COM) DDG approach, specifically with regard to motion management of target structures in future radiotherapy planning applications. Methods PET list mode datasets acquired in one bed position of 19 different radiotherapy patients undergoing pretreatment [18F]FDG PET/CT or [18F]FDG PET/MRI were included into this retrospective study. All scans were performed over a region with organs (myocardium, kidneys) or tumor lesions of high tracer uptake and under free breathing. Aside from the original list mode data, datasets with progressively decreasing PET statistics were generated. From these, COM DDG signals were derived for subsequent amplitude‐based gating of the original list mode file. The apparent respiratory shift d from end‐expiration to end‐inspiration was determined from the gated images and expressed as a function of signal‐to‐noise ratio SNR of the determined gating signals. This relation was tested against additional 25 [18F]FDG PET/MRI list mode datasets where high‐precision MR navigator‐like respiratory signals were available as reference signal for respiratory gating of PET data, and data from a dedicated thorax phantom scan. Results All original 19 high‐quality list mode datasets demonstrated the same behavior in terms of motion resolution when reducing the amount of list mode events for DDG signal generation. Ratios and directions of respiratory shifts between end‐respiratory gates and the respective nongated image were constant over all statistic levels. Motion resolution d/dmax could be modeled as urn:x-wiley:00942405:media:mp12987:mp12987-math-0001, with dmax as the actual respiratory shift. Determining dmax from d and SNR in the 25 test datasets and the phantom scan demonstrated no significant differences to the MR navigator‐derived shift values and the predefined shift, respectively. Conclusions The SNR can serve as a general metric to assess the success of COM‐based DDG, even in different scanners and patients. The derived formula for motion resolution can be used to estimate the actual motion extent reasonably well in cases of limited PET raw data statistics. This may be of interest for individualized radiotherapy treatment planning procedures of target structures subjected to respiratory motion.

PSMA-targeted PET in patients with prostate cancer (PCa) has a significant impact on treatment decisions. By far the most frequently used PSMA ligand is 68Ga-labelled PSMA-11. However, due to the availability of larger amounts of activity, 18F-labelled PSMA ligands are of major interest. The aim of the present study was to evaluate the biodistribution and performance of the novel 18F-labelled ligand PSMA-1007 at two different time points. This retrospective analysis included 40 consecutive patients (mean age 68.7 ± 8.1 years) referred for PSMA PET/CT. 18F-PSMA-1007 PET/CT was performed for localization of biochemical relapse, primary staging or therapy follow-up. Circular regions of interest were placed on representative slices of the liver, spleen, kidney, abdominal aortic blood pool, bone marrow (fourth lumbar vertebral body), urinary bladder and gluteus muscle at 60 and 120 min after injection. In malignant lesions the maximum standardized uptake (SUVmax) was measured within volumes of interest at both time points. All SUVs at 60 min were compared with those at 120 min after injection. The activity in the blood pool, urinary bladder and gluteus muscle was very low and decreased significantly over time (P

Prostate-specific membrane antigen (PSMA) is the up-and-coming target for molecular imaging of prostate cancer. Despite its name, non-prostate-related PSMA expression in physiologic tissue as well as in benign and malignant disease has been reported in various publications. Unlike in prostate cancer, PSMA expression is only rarely observed in non-prostate tumor cells. Instead, expression occurs in endothelial cells of tumor-associated neovasculature, although no endothelial expression is observed under physiologic conditions. The resulting potential for tumor staging in non-prostate malignant tumors has been demonstrated in first patient studies. This review summarizes the first clinical studies and deduces future perspectives in staging, molecular characterization, and PSMA-targeted radionuclide therapy based on histopathologic examinations of PSMA expression. The non-exclusivity of PSMA in prostate cancer opens a window to utilize the spectrum of available radioactive PSMA ligands for imaging and molecular characterization and maybe even therapy of non-prostate disease.

Die Bildgebung spielt eine wichtige Rolle bei der Auswahl derjenigen Patienten mit metastasiertem, kastrastionsrefraktärem Prostatakarzinom, die für eine 223Ra-Dichlorid-Therapie von Knochenmetastasen geeignet sind. Das Ziel dieser Studie war zu untersuchen, ob eine zusätzliche 68Ga-PSMA-PET einen inkrementellen Nutzen gegenüber der konventionellen Bildgebung bei der Auswahl geeigneter Patienten für diese Therapie aufweist.Bei 27 konsekutiv für eine 223Ra- Dichlorid-Therapie vorgestellten Patienten wurde eine zusätzliche 68Ga-PSMA-PET/CT durchgeführt. Die Tracerverteilung wurde systematisch ausgewertet in Hinblick auf die Detektion von viszeralen Metastasen und von ossären Metastasen ohne adäquate Speicherung in der Skelettszintigraphie.Zusätzliche viszerale Metastasen wurden mittels 68Ga-PSMA-PET bei 4 Patienten (15 %) detektiert (3 Leber, 1 Nebenniere), wobei in der Folge das therapeutische Vorgehen bei 2 der 4 Patienten geändert wurde. Mit der PET wurde eine ausgedehntere Knochenmetastasierung im Vergleich zur Skelettszintigraphie bei 9 Patienten (33 %) nachgewiesen. Bei dreien dieser Patienten war der “Mismatch” ausgedehnt genug, um die Durchführung der 223Ra-Dichlorid-Therapie in Frage zu stellen.Die zusätzliche Durchführung einer 68Ga-PSMA-PET als Torwächter zwischen konventioneller Bildgebung und der 223Ra-Dichlorid-Therapie kann wichtige zusätzliche Informationen liefern über das Vorliegen von viszeralen Metastasen und von ossären Tumormanifestationen ohne adäquaten Knochenstoffwechsel. Dieses kann bei einer signifikanten Zahl von Patienten zu einer Änderung des therapeutischen Managements führen und sollte in zukünftigen klinischen Studien berücksichtigt werden.

SummaryPurpose: Medical imaging plays an important role in selecting patients with metastatic castration-resistant prostate cancer for 223Ra- dichloride therapy of bone metastases. The purpose of this study was to investigate whether 68Ga-PSMA-PET has incremental value over conventional imaging for selecting patients suitable for 223Ra-dichloride therapy. Methods: In 27 consecutive patients referred for 223Ra-dichloride therapy additional 68Ga-PSMA-PET/CT was performed and tracer distribution was evaluated systematically with respect to the detection of visceral metastases and bone metastases with inadequate uptake on bone scintigraphy. Results: In 4 patients (15 %) 68Ga- PSMA-PET revealed previously unknown visceral metastases (3 liver, 1 adrenal gland), which changed the therapeutic decision in 2 cases. PET revealed more extended tumour involvement in the bone compared to bone scintigraphy in 9 patients (33 %). In 3 of these, the mismatch was extensive enough to question suitability for 223Ra-dichloride therapy. Conclusions: Additional 68Ga-PSMA-PET as a gatekeeper between conventional staging and 223Ra-dichloride therapy can provide valuable additional information with regard to visceral metastases and tumour manifestations without adequate bone mineral turnover. It may lead to a change in therapeutic management in a significant number of patients and should therefore be considered in future clinical trials.

The aim of this study was to evaluate the efficacy of 177Lu-prostate-specific membrane antigen (PSMA)-617 (177Lu-PSMA) and selective internal radiation therapy (SIRT) for the treatment of liver metastases of castration-resistant prostate cancer. Methods: Safety and survival of patients with metastatic castration-resistant prostate cancer and liver metastases assigned to 177Lu-PSMA alone (n = 31) or in combination with SIRT (n = 5) were retrospectively analyzed. Additionally, a subgroup (n = 10) was analyzed using morphologic and molecular response criteria. Results: Median estimated survival was 5.7 mo for 177Lu-PSMA alone and 8.4 mo for combined sequential 177Lu-PSMA and SIRT. 177Lu-PSMA achieved discordant therapy responses with both regressive and progressive liver metastases in the same patient (best vs. worst responding metastases per patient: -35% vs. +63% diameter change; P < 0.05). SIRT was superior to 177Lu-PSMA for the treatment of liver metastases (0% vs. 56% progression). Conclusion: The combination of 177Lu-PSMA and SIRT is efficient and feasible for the treatment of advanced prostate cancer. 177Lu-PSMA alone seems to have limited response rates in the treatment of liver metastases.

Despite progress in treatment of metastatic castration-resistant prostate cancer (mCRPC), new approaches are urgently needed. Recently theranostic concepts using radiolabeled ligands of the prostate-specific membrane antigen (PSMA) have been developed for diagnostics and therapy of patients with advanced mCRPC. The aim of this study was to evaluate tumor response, adverse effects, and survival in patients undergoing radioligand therapy with Lu-PSMA-617.Fifty therapies using Lu-PSMA-617 were performed in 28 consecutive patients with mCRPC and exhausted conventional therapeutic options (median age, 73.4 years; range, 45-87 years). Data were retrospectively analyzed with focus on response, safety, and survival. The median overall survival was compared with that of a recent historical patient cohort treated with best supportive care prior to availability of Lu-PSMA-617.Any PSA decline occurred in 59% and 75% of patients after 1 and 2 therapies. Moreover, a PSA decline of 50% or greater occurred in 32% and 50%. Therapies were well tolerated. Hematologic and renal parameters changed insignificantly; permanent xerostomia or other safety-related toxicity did not occur. The estimated median survival was 29.4 weeks, significantly longer than survival in the historical best supportive care group (19.7 weeks [hazard ratio, 0.44; 95% confidence interval, 0.20-0.95]; P = 0.031).Results from 50 therapies show that radioligand therapy with Lu-PSMA-617 is effective and well tolerated and seems to increase overall survival. A future randomized controlled prospective study will be necessary to confirm these results.

Introduction Patients with radioiodine-refractory differentiated thyroid cancer (RrDTC) have a rather poor prognosis and are in need of novel treatments. As RrDTCs can in some cases express somatostatin receptors (SSRT), targeting of these receptors by Ga/Lu-DOTATATE could evolve as a novel theranostic option. Methods Five RrDTC patients with limited further therapeutic options and documented expression of SSRT using Ga-DOTATATE-PET/CT received 2 to 4 cycles of PRRT with Lu-DOTATATE. Response to therapy was assessed by thyroglobulin (Tg) and morphological and metabolic criteria based on interim and follow-up Ga-DOTATATE-PET/CTs. Analysis was performed on a per-patient basis. Results In the post-therapy evaluation, only one out of five patients showed a partial response, whereas three patients had a progressive disease. One patient had discordant findings between stable imaging results albeit rising Tg levels. Conclusion In this case study of five patients, Lu-DOTATATE therapy showed only heterogeneous response and efficacy in RrDTC patients despite good lesional uptake in pre-therapeutic PET.

The Cooperative Ewing Sarcoma Study and the Late Effects Surveillance System of the Society for Paediatric Oncology and Haematology recommend a structured follow-up imaging protocol (FUIP) for patients with Ewing sarcoma (EwS) with decreasing frequency of imaging over the first 5 years. The present study aims to assess the effectiveness of the FUIP for EwS patients regarding survival after relapse. A retrospective multicenter analysis on 160 eligible patients with EwS recurrence was performed. Potential survival differences following recurrence diagnosis between patients with protocol-detected and symptomatic relapse were investigated using the Kaplan-Meier method. Additional subgroup analyses were performed on the relapse type. Overall survival (OS) was calculated from diagnosis of relapse to last follow-up or death. In the multicenter analysis, recurrence was detected by FUIP in 77 of 160 patients (48%) and due to symptoms in 83 patients (52%). Regarding the entire study population, OS was significantly superior in patients with protocol-detected relapse compared to patients with symptomatic relapse (median, 2.4 vs. 1.2 years; P < 0.001). In the subgroup analyses, patients whose lung recurrences were detected by the FUIP experienced longer survival after recurrence than those whose recurrences were detected symptomatically (P = 0.023). In the 83 symptomatic patients, pain was the most prevalent symptom of relapse (72%). FUIP may benefit survival in EwS relapse, especially in lung recurrence. Pain was the leading symptom of relapse

Objective: The aim of this pilot study was to test and demonstrate the feasibility of simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) of the head and upper neck area using a new hybrid PET/MRI system. Methods: Eight patients with malignant head and neck tumours were included in the pilot study. Directly after routine PET/CT imaging with a whole-body system using the glucose derivative 2-[18F]fluoro-2deoxy-D-glucose (FDG) as a radiotracer additional measurements were performed with a prototype PET/MRI system for simultaneous PET and MR imaging. Physiological radiotracer uptake within regular anatomical structures as well as tumour uptake were evaluated visually and semiquantitatively (metabolic ratios) in relation to cerebellar uptake on the PET/MRI and PET/CT systems. Results: The MR datasets showed excellent image quality without any recognisable artefacts caused by the inserted PET system. PET images obtained with the PET/MRI system exhibited better detailed resolution and greater image contrast in comparison to those from the PET/CT system. An excellent agreement between metabolic ratios obtained with both PET systems was found: R = 0.99 for structures with physiological tracer uptake, R = 0.96 for tumours. Conclusion: Simultaneous PET/MRI of the head and upper neck area is feasible with the new hybrid PET/MRI prototype

Ga-PSMA-11 PET/CT was performed in a 74-year-old man because of biochemical recurrence of prostate cancer following radiation therapy of the prostate gland 24 months earlier. Besides focal nuclide accumulation in the prostate gland suggestive of local recurrence, PET scan revealed no further pathologic uptake. However, CT showed multiple pulmonic nodules suggestive of metastases. Thoracotomy and pathologic examination revealed the nodules to be prostate cancer metastasis. Furthermore, immunohistochemical staining with PSMA antibodies demonstrated a virtual lack of PSMA expression. This case demonstrates the possibility of PSMA-negative metastases of prostate cancer an important pitfall that should be known to physicians interpreting PSMA PET.

To evaluate the performance of a prospectively defined follow-up imaging protocol that includes FDG-PET(/CT) to detect tumour recurrence in Ewing sarcoma (EwS) before becoming symptomatic.Imaging results and clinical data during follow-up were retrospectively analysed from all patients treated successfully within the EURO E.W.I.N.G. 99 trial at the University Hospital Münster, Germany. All patients received follow-up imaging according to a comprehensive protocol that included regular X-ray, CT, MRI, bone scan and PET(/CT), albeit not all on the same day and with varying intervals for the different modalities.80 of 105 patients underwent follow-up at our institution after complete remission. 30 patients had recurrent tumour during the follow-up period of 3.6 years on average. 19 recurrences (63%) were detected by scheduled imaging before the advent of clinical symptoms. The majority of these recurrences (8 out of 19; 42%) was detected first by PET/ CT (and confirmed with additional imaging thereafter), even though the total number of PET/CTs was comparatively low (138) and PET/CT was not systematically scheduled before other imaging techniques. Recurrences detected by bone scan were also detectable by PET.The implemented follow-up protocol was effective in the detection of EwS recurrence before the advent of symptoms. Most cases of those detected before onset of symptoms were detected by PET/CT first. This hybrid imaging modality should therefore be considered in the routine follow-up of EwS patients, as is standard in our hospital. In combination with PET, low-dose chest CT seems to be sufficient in the detection of small pulmonary nodules.ZIEL:: Evaluation eines prospektiv definierten bildgebenden Nachsorge-Protokolls einschließlich FDG-PET(/CT) zur Erkennung von Rezidiven eines Ewing-Sarkoms (EwS) vor dem Auftreten von Symptomen.Die Ergebnisse der Bildgebung und klinische Daten im Rahmen der Nachsorge wurden retrospektiv bei allen Patienten erhoben, die erfolgreich innerhalb der EURO E.W.I.N.G 99 Studie am Universitätsklinikum Münster behandelt wurden. Alle Patienten erhielten eine Nachsorge gemäß einem umfassenden Bildgebungs-Protokoll, welches regelmäßige Röntgenuntersuchungen, CT, MRT, Skelett-Szintigraphie und PET(/CT) beinhaltete, die allerdings nicht alle am selben Tag und mit unterschiedlichen Intervallen für die einzelnen Modalitäten durchgeführt wurden.80 von 105 Patienten erhielten eine Nachsorge in unserem Zentrum nach kompletter Remission. 30 Patienten erlitten ein Rezidiv innerhalb der Nachsorgeperiode von durchschnittlich 3,6 Jahren. 19 Rezidive (63 %) wurden durch die vorgegebene Bildgebung vor dem Auftreten von Symptomen entdeckt. Die Mehrzahl (8 von 19; 42%) der so entdeckten Rezidive wurde als erstes durch PET/CT-Untersuchungen erkannt (und danach durch andere Bildgebungsmethoden bestätigt), obwohl die Gesamtzahl der durchgeführten PET/CTs vergleichsweise gering war (138) und diese Untersuchung nicht systematisch vor anderen Bildgebungsverfahren terminiert wurde. Rezidive, welche durch die Skelett-Szintigraphie entdeckt wurden, waren auch in der PET erkennbar.Das implementierte Bildgebungs-Nachsorgeprotokoll erwies sich als effektiv darin, EwS-Rezidive vor Symptom-Manifestation zu entdecken. Die meisten der vor Auftreten von Symptomen detektierten Rezidive wurden zuerst durch die PET/CT nachgewiesen. Die PET/CT sollte daher in die Nachsorge von EwS-Patienten eingeschlossen werden, so wie es bereits in unserem Klinikum Standard ist. In Kombination mit PET scheint die Low-dose-ThoraxCT suffizient zur Erkennung kleiner pulmonaler Läsionen zu sein.

In this chapter, typical clinical whole-body applications of magnetic resonance-positron emission tomography (MR-PET) are presented. Most current whole-body applications stem from the field of oncology. However, non-malignant tumours and benign diseases associated with inflammation and infection are also suitable diseases for examination using MR-PET. The start of the chapter deals with general considerations relating to the advantages and disadvantages of whole-body MR-PET, especially in comparison to PET-computed tomography (CT). It then continues with oncological imaging, giving examples of diseases that the authors feel MR-PET promises significant advantages over PET-CT. Singular examples of non-malignant tumours and other benign diseases are considered thereafter. Clinical applications of motion correction conclude the chapter.

PET using the radiotracer F-fluorodeoxyglucose (FDG) was performed in a patient who presented with elevated thyroglobulin (Tg) levels several years after initial therapy of follicular thyroid carcinoma (oncocytic variant) and in whom high-dose radioiodine (I) failed to locate recurrent tumor or to decrease Tg levels. A focal fluorodeoxyglucose uptake in the apical septum of the heart did not have a discernible correlate in echocardiography or MRI for more than 12 months. Finally, a metastasis of the follicular thyroid carcinoma with partly squamous cell differentiation was confirmed and treated by resection and stereotactic body radiotherapy.

A 65-year-old man with disseminated bone metastases of prostate cancer was referred for Ga-PSMA-HBED-CC-PET/CT (short PSMA-PET/CT) to exclude visceral metastases before treatment of bone metastases with Ra-dichloride. Apart from disseminated bone metastases, PSMA-PET/CT revealed a focal cerebral tracer uptake in the right frontal lobe highly suspicious for cerebral spread. According to patient history, a cerebral infarction occurred 14 days before PSMA imaging in corresponding localization confirmed by MRI scanning. This case demonstrates the possibility of false-positive finding of cerebral metastases in PSMA-PET early after stroke.

Background Attenuation correction is one of the most important steps in producing quantitative PET image data. In hybrid PET-MRI systems, this correction is far from trivial, as MRI data are not correlated to PET attenuation properties of the scanned object. Commercially available systems often employ correction schemes based on segmenting the body into different tissue classes (air, lung tissue, fat-, and water-like soft tissue), e.g. by using a dual time-point Dixon sequence. However, several pitfalls are known for this approach. Here a specific artefact of MR-based PET attenuation correction is reported, caused by misidentifying the liver as lung tissue due to iron overload. Case presentation A patient with a history of hematopoietic stem cell transplantation underwent a whole-body [18F]FDG PET-MRI scan. Markedly low liver uptake values were noted in the PET images, seemingly caused by an erroneous assignment of lung tissue attenuation values to the liver. A closer investigation demonstrated markedly low MRI intensity values of the liver, indicative of secondary hemochromatosis (iron overload) most probably due to a history of multiple blood transfusions. Manual assignment of adequate liver attenuation values resulted in more realistic PET images. Conclusions Iron overload of the liver was identified as a cause of a specific attenuation correction artefact. It remains to be seen how frequent this artefact will be encountered; however, this case highlights that attenuation maps should always be checked during PET image interpretation in hybrid PET-MRI.

ObjectiveWe investigated the impact of cardiac presynaptic norepinephrine recycling in patients with long-QT syndrome (LQTS) using positron emission tomography (PET) with 11C-meta-hydroxyephedrine ([11C]mHED-PET).Methods[11C]mHED-PET was performed in 25 patients with LQTS (LQT1: n=14; LQT2: n=11) and 20 healthy controls and correlated with clinical parameters. [11C]mHED-PET images were analysed for global and regional retention indices (RI) and washout rates (WO) reflecting dynamic parameters of the tracer activity.ResultsGlobal and regional RI values were similar between patients with LQTS and controls. Although the global WO rates were similar between these groups, regional WO rates were on average higher in the lateral left ventricle (LV) wall in patients with LQTS (dose, mean ±SD; 0.08±0.14 vs 0.00%±0.09% min–1; p=0.033). In addition, patients with LQTS with a longer QTc interval showed a higher global WO rate. Clinical symptoms correlated with higher global WO rates. In the presence of normal global WO rates, asymptomatic LQTS patients showed higher global RI values.ConclusionThe increased regional WO rate of [11C]mHED in the lateral LV suggests an imbalance of presynaptic catecholamine reuptake and release, resulting in a higher synaptic catecholamine concentration, in particular in LQT1 patients. This might enhance β-adrenoceptor signalling and thereby aggravate inherited ion channel dysfunction and may facilitate occurrence of ventricular tachyarrhythmias. Detection of regional differences in LV sympathetic nervous function may modify disease expression and potentially serve as a non-invasive risk marker in congenital LQTS.Trial registration number2006-002767-41;Results.

Background While 68Ga-PSMA PET-MRI might be superior to PET-CT with regard to soft tissue assessment in prostate cancer evaluation, it is also known to potentially introduce additional PET image artefacts. Therefore, the impact of PET acquisition duration and attenuation data on artefact occurrence, lesion detectability, and quantification was investigated. To this end, whole-body PET list mode data from 12 patients with prostate cancer were acquired 1 h after injection of 2 MBq/kg [68Ga]HBED-CC-PSMA on a hybrid PET-MRI system. List mode data were further transformed into data sets representing 300, 180, 90, and 30 s acquisition duration per bed position. Standard attenuation and scatter corrections were performed based on MRI-derived attenuation maps, complemented by emission-based attenuation data in areas not covered by MRI. A total of 288 image data sets were reconstructed with varying acquisition durations for emission and attenuation data with and without scatter and prompt gamma correction, and further analysed regarding image quality and diagnostic performance. Results Decreased PET acquisition durations resulted in a significantly increased incidence of halo artefacts around kidneys and bladder, decreased lesion detectability and lower SUV as well as markedly lower arm attenuation values: Halo artefacts were present in 5 out of 12 cases at 300-s duration, in 6 at 180 s, in 10 at 90 s, and in 11 cases at 30 s. Using attenuation data of the 300 s scans restored artefact occurrence to the original 300-s level. Prompt gamma correction only led to small improvements in terms of artefact occurrence and size. Of the 141 detected lesions in the 300-s images one lesion was not detected at 180 s, 28 at 90 s, and 64 at 30 s. Using the 300-s attenuation map decreased non-detectability of lesions to zero at 180 s, 9 at 90 s, and 52 at 30 s. Attenuation maps at 90 and 30 s demonstrated markedly lower mean arm attenuation values (0.002 cm-1) than those at 300 s (0.084 cm-1), and 180 s (0.062 cm-1). Conclusions Short acquisition durations of less than 3 minutes per bed position result in unacceptable image artefacts and decreased diagnostic performance in current whole-body 68Ga-PSMA PET-MRI and should be avoided. Increased image noise and imperfections in generated attenuation maps were identified as a paramount cause for image degradation. Electronic supplementary material The online version of this article (doi:10.1186/s13550-017-0261-8) contains supplementary material, which is available to authorized users.

Despite enormous investment into cardiovascular research on all levels worldwide, cardiovascular events such as myocardial infarction, heart failure, tachyarrhythmia or stroke remain the major causes for death and inability in all developed countries. Conventional clinical cardiovascular imaging nowadays provides high-resolution visualisation of the morphology of vessels and the myocardium. To translate the available patient imaging technologies into animals, especially mice where genetic technologies can be used to induce human-like pathophysiologies, is of great interest for cardiovascular research. Furthermore, new imaging biomarkers for targeting molecular processes such as inflammation in atherosclerosis are being developed which have to be tested and optimised in animal models (again mice are of greatest interest here) before potentially translated into the clinics. Imaging of the heart and the vessels of small rodents such as mice poses significant challenges for small animal imaging systems with respect to the spatial and temporal resolution. This chapter elucidates the relevant cardiovascular pathologies and clinical challenges, reviews animal models of cardiovascular disease and shows examples of applications of small animal imaging by CT, ultrasound, MRI, SPECT, PET and optical imaging.

Summary Aim: To evaluate the performance of a prospectively defined follow-up imaging protocol that includes FDG-PET(/CT) to detect tumour recurrence in Ewing sarcoma (EwS) before becoming symptomatic. Methods: Imaging results and clinical data during follow-up were retrospectively analysed from all patients treated successfully within the EURO E.W.I.N.G. 99 trial at the University Hospital Münster, Germany. All patients received follow-up imaging according to a comprehensive protocol that included regular X-ray, CT, MRI, bone scan and PET(/CT), albeit not all on the same day and with varying intervals for the different modalities. Results: 80 of 105 patients underwent follow-up at our institution after complete remission. 30 patients had recurrent tumour during the follow-up period of 3.6 years on average. 19 recurrences (63%) were detected by scheduled imaging before the advent of clinical symptoms. The majority of these recurrences (8 out of 19; 42%) was detected first by PET/ CT (and confirmed with additional imaging thereafter), even though the total number of PET/CTs was comparatively low (138) and PET/CT was not systematically scheduled before other imaging techniques. Recurrences detected by bone scan were also detectable by PET.Conclusions: The implemented follow-up protocol was effective in the detection of EwS recurrence before the advent of symptoms. Most cases of those detected before onset of symptoms were detected by PET/CT first. This hybrid imaging modality should therefore be considered in the routine follow-up of EwS patients, as is standard in our hospital. In combination with PET, low-dose chest CT seems to be sufficient in the detection of small pulmonary nodules.

Nivolumab in a patient with refractory Hodgkin’s lymphoma after allogeneic stem cell transplantation

Coronary artery calcium scoring can complement myocardial perfusion imaging (MPI). The purpose of this study was to evaluate the feasibility and accuracy of using the CalciumScore-CT derived from a combined SPECT/CT device also for SPECT attenuation correction (AC).The study group comprised 99 patients who underwent both post-stress and rest MPI using a two-slice SPECT/CT system. For AC, one of the two scans was accompanied by a CalciumScore-CT scan (CalciumScore-CTAC) and the other by a conventional spiral CT (AttenCorr-CT) scan (AttenCorr-CTAC). In 48 patients the CalciumScore-CT scan was acquired with the post-stress scan and the AttenCorr-CT scan with the rest scan, and in 51 patients the order was reversed. The accuracy of the images based on AC was determined qualitatively by consensus reading with respect to the clinical diagnoses as well as quantitatively by comparing the perfusion summed stress scores (SSS) and the summed rest scores (SRS) between attenuation-corrected and uncorrected images.In comparison to the uncorrected images CalciumScore-CTAC led to regional inaccuracies in 14 of 51 of studies (27.5%) versus 12 of 48 studies (25%) with AttenCorr-CTAC for the stress studies and in 5 of 48 (10%) versus 1 of 51 (2%) for the rest studies, respectively. This led to intermediate and definite changes in the final diagnosis (ischaemia and/or scarring) in 12% of the studies (12 of 99) and in 7% of the studies (7 of 99) with CalciumScore-CTAC and in 9% of the studies (9 of 99) and 4% of the studies (4 of 99) with AttenCorr-CTAC. Differences in SSS and SRS with respect to the uncorrected images were greater for the CalciumScore-CTAC images than for the AttenCorr-CTAC images (ΔSSS 4.5 ± 5.6 and 2.1 ± 4.4, p = 0.023; ΔSRS 4.2 ± 4.9 and 1.6 ± 3.2, p = 0.004, respectively).Using the same CT scan for calcium scoring and SPECT AC is feasible. Image interpretation must, however, include uncorrected images since CT-based AC relatively often introduces artefacts into the myocardial perfusion images. This effect is somewhat more pronounced with CalciumScore-CTAC than with AttenCorr-CTAC.