Combining PSMA-PET and PROMISE to re-define disease stage and risk in patients with prostate cancer: a multicentre retrospective study.

BACKGROUND: Prostate-specific membrane antigen (PSMA)-PET was introduced into clinical practice in 2012 and has since transformed the staging of prostate cancer. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were proposed to standardise PSMA-PET reporting. We aimed to compare the prognostic value of PSMA-PET by PROMISE (PPP) stage with established clinical nomograms in a large prostate cancer dataset with follow-up data for overall survival. METHODS: In this multicentre retrospective study, we used data from patients of any age with histologically proven prostate cancer who underwent PSMA-PET at the University Hospitals in Essen, Münster, Freiburg, and Dresden, Germany, between Oct 30, 2014, and Dec 27, 2021. We linked a subset of patient hospital records with patient data, including mortality data, from the Cancer Registry North-Rhine Westphalia, Germany. Patients from Essen University Hospital were randomly assigned to the development or internal validation cohorts (2:1). Patients from Münster, Freiburg, and Dresden University Hospitals were included in an external validation cohort. Using the development cohort, we created quantitative and visual PPP nomograms based on Cox regression models, assessing potential PPP predictors for overall survival, with least absolute shrinkage and selection operator penalty for overall survival as the primary endpoint. Performance was measured using Harrell's C-index in the internal and external validation cohorts and compared with established clinical risk scores (International Staging Collaboration for Cancer of the Prostate [STARCAP], European Association of Urology [EAU], and National Comprehensive Cancer Network [NCCN] risk scores) and a previous nomogram defined by Gafita et al (hereafter referred to as GAFITA) using receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) estimates. FINDINGS: We analysed 2414 male patients (1110 included in the development cohort, 502 in the internal cohort, and 802 in the external validation cohort), among whom 901 (37%) had died as of data cutoff (June 30, 2023; median follow-up of 52·9 months [IQR 33·9-79·0]). Predictors in the quantitative PPP nomogram were locoregional lymph node metastases (molecular imaging N2), distant metastases (extrapelvic nodal metastases, bone metastases [disseminated or diffuse marrow involvement], and organ metastases), tumour volume (in L), and tumour mean standardised uptake value. Predictors in the visual PPP nomogram were distant metastases (extrapelvic nodal metastases, bone metastases [disseminated or diffuse marrow involvement], and organ metastases) and total tumour lesion count. In the internal and external validation cohorts, C-indices were 0·80 (95% CI 0·77-0·84) and 0·77 (0·75-0·78) for the quantitative nomogram, respectively, and 0·78 (0·75-0·82) and 0·77 (0·75-0·78) for the visual nomogram, respectively. In the combined development and internal validation cohort, the quantitative PPP nomogram was superior to STARCAP risk score for patients at initial staging (n=139 with available staging data; AUC 0·73 vs 0·54; p=0·018), EAU risk score at biochemical recurrence (n=412; 0·69 vs 0·52; p<0·0001), and NCCN pan-stage risk score (n=1534; 0·81 vs 0·74; p<0·0001) for the prediction of overall survival, but was similar to GAFITA nomogram for metastatic hormone-sensitive prostate cancer (mHSPC; n=122; 0·76 vs 0·72; p=0·49) and metastatic castration-resistant prostate cancer (mCRPC; n=270; 0·67 vs 0·75; p=0·20). The visual PPP nomogram was superior to EAU at biochemical recurrence (n=414; 0·64 vs 0·52; p=0·0004) and NCCN across all stages (n=1544; 0·79 vs 0·73; p<0·0001), but similar to STARCAP for initial staging (n=140; 0·56 vs 0·53; p=0·74) and GAFITA for mHSPC (n=122; 0·74 vs 0·72; p=0·66) and mCRPC (n=270; 0·71 vs 0·75; p=0·23). INTERPRETATION: Our PPP nomograms accurately stratify high-risk and low-risk groups for overall survival in early and late stages of prostate cancer and yield equal or superior prediction accuracy compared with established clinical risk tools. Validation and improvement of the nomograms with long-term follow-up is ongoing (NCT06320223). FUNDING: Cancer Registry North-Rhine Westphalia.

Comparison of image quality and spatial resolution between 18F, 68Ga, and 64Cu phantom measurements using a digital Biograph Vision PET/CT.

BACKGROUND: PET nuclides can have a considerable influence on the spatial resolution and image quality of PET/CT scans, which can influence diagnostics in oncology, for example. The individual impact of the positron energy of 18F, 68Ga, and 64Cu on spatial resolution and image quality was compared for PET/CT scans acquired using a clinical, digital scanner. METHODS: A Jaszczak phantom and a NEMA PET body phantom were filled with 18F-FDG, 68Ga-HCl, or 64Cu-HCl, and PET/CT scans were performed on a Siemens Biograph Vision. Acquired images were analyzed regarding spatial resolution and image quality (recovery coefficients (RC), coefficient of variation within the background, contrast recovery coefficient (CRC), contrast-noise ratio (CNR), and relative count error in the lung insert). Data were compared between scans with different nuclides. RESULTS: We found that image quality was comparable between 18F-FDG and 64Cu-HCl PET/CT measurements featuring similar maximal endpoint energies of the positrons. In comparison, RC, CRC, and CNR were degraded in 68Ga-HCl data despite similar count rates. In particular, the two smallest spheres of 10 mm and 13 mm diameter revealed lower RC, CRC, and CNR values. The spatial resolution was similar between 18F-FDG and 64Cu-HCl but up to 18% and 23% worse compared with PET/CT images of the NEMA PET body phantom filled with 68Ga-HCl. CONCLUSIONS: The positron energy of the PET nuclide influences the spatial resolution and image quality of a digital PET/CT scan. The image quality and spatial resolution of 68Ga-HCl PET/CT images were worse than those of 18F-FDG or 64Cu-HCl despite similar count rates.

[Influence of therapeutic temperature management on the clinical course in patients after in-hospital cardiac arrest : A retrospective analysis]. / Einfluss des therapeutischen Temperaturmanagements auf den klinischen Verlauf bei intrahospital reanimierten Patienten : Eine retrospektive Analyse.

METHODS: Retrospective analysis of all patients with in-hospital cardiac arrest and return of spontaneous circulation (ROSC) in the ICU of the cardiologic department of the University Hospital of Halle (Saale) between 1999 and 2009. RESULTS: During the observation period, 169 patients with in-hospital cardiac arrest and information regarding temperature measurements were treated. Invasive therapeutic temperature management (TTM+) was applied in 64 patients (37.9%), while 105 patients (62.1%) underwent no therapeutic temperature management (TTM-). TTM+ and TTM- showed no relevant differences regarding patient age (TTM+: 67.6 ± 12.6 years; TTM-: 69.8 ± 12.6 years; p = 0.257), comorbidities and the initial rhythm; however, there were more men in the TTM+ group (76.6% vs. 58.1%; p = 0.015). All patients had been intubated. Time until ROSC in TTM+ was significantly longer (25.9 ± 25.8 min vs. 15.0 ± 12.4 min; p < 0.005). TTM+ resulted in a lower 30-day survival and an unfavourable neurologic outcome (Glasgow outcome scale I or II: 75% TTM+ vs. 55.2% TTM-). This negative effect persisted after adjustment for age of the patients, but not after adjustment for age and duration of reanimation (nonadjusted odds ratio for adverse neurologic outcome under TTM+: 0.411 (p = 0.011); odds ratio after adjusting for age: 0.361 (p = 0.09); odds ratio after adjusting for age and duration of the reanimation: 0.505 (p = 0.121)).

PET/CT imaging of head-and-neck and pancreatic cancer in humans by targeting the "Cancer Integrin" αvß6 with Ga-68-Trivehexin.

PURPOSE: To develop a new probe for the αvß6-integrin and assess its potential for PET imaging of carcinomas. METHODS: Ga-68-Trivehexin was synthesized by trimerization of the optimized αvß6-integrin selective cyclic nonapeptide Tyr2 (sequence: c[YRGDLAYp(NMe)K]) on the TRAP chelator core, followed by automated labeling with Ga-68. The tracer was characterized by ELISA for activities towards integrin subtypes αvß6, αvß8, αvß3, and α5ß1, as well as by cell binding assays on H2009 (αvß6-positive) and MDA-MB-231 (αvß6-negative) cells. SCID-mice bearing subcutaneous xenografts of the same cell lines were used for dynamic (90 min) and static (75 min p.i.) µPET imaging, as well as for biodistribution (90 min p.i.). Structure-activity-relationships were established by comparison with the predecessor compound Ga-68-TRAP(AvB6)3. Ga-68-Trivehexin was tested for in-human PET/CT imaging of HNSCC, parotideal adenocarcinoma, and metastatic PDAC. RESULTS: Ga-68-Trivehexin showed a high αvß6-integrin affinity (IC50 = 0.047 nM), selectivity over other subtypes (IC50-based factors: αvß8, 131; αvß3, 57; α5ß1, 468), blockable uptake in H2009 cells, and negligible uptake in MDA-MB-231 cells. Biodistribution and preclinical PET imaging confirmed a high target-specific uptake in tumor and a low non-specific uptake in other organs and tissues except the excretory organs (kidneys and urinary bladder). Preclinical PET corresponded well to in-human results, showing high and persistent uptake in metastatic PDAC and HNSCC (SUVmax = 10-13) as well as in kidneys/urine. Ga-68-Trivehexin enabled PET/CT imaging of small PDAC metastases and showed high uptake in HNSCC but not in tumor-associated inflammation. CONCLUSIONS: Ga-68-Trivehexin is a valuable probe for imaging of αvß6-integrin expression in human cancers.

Intraindividual comparison of [68 Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 in prostate cancer patients: a retrospective single-center analysis.

BACKGROUND: The analysis aimed to compare the radiotracers [68Ga]-Ga-PSMA-11 and [18F]-F-PSMA-1007 intraindividually in terms of malignant lesions, mi(molecular-imaging)TNM staging and presumable unspecific lesions retrospectively as used in routine clinical practice. METHODS: A retrospective analysis of 46 prostate cancer patients (median age: 71 years) who underwent consecutive [68Ga]-Ga-PSMA-11- and [18F]-F-PSMA-1007-PET/CT or PET/MRI within a mean of 12 ± 8.0 days was performed. MiTNM staging was performed in both studies by two nuclear medicine physicians who were blinded to the results of the other tracer. After intradisciplinary and interdisciplinary consensus with two radiologists was reached, differences in both malignant and presumable nonspecific tracer accumulation were analyzed. RESULTS: Differences in terms of miTNM stages in both studies occurred in nine of the 46 patients (19.6%). The miT stages differed in five patients (10.9%), the miN stages differed in three patients (6.5%), and different miM stages occurred only in one patient who was upstaged in [18F]-F-PSMA-1007 PET. Concordant miTNM stages were obtained in 37 patients (80.4%). There was no significant difference between [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11 in the SUVmax locally (31.5 vs. 32.7; p = 0.658), in lymph node metastases (28.9 vs. 24.9; p = 0.30) or in bone metastases (22.9 vs. 27.6; p = 0.286). In [18F]-F-PSMA-1007 PET, more patients featured presumable unspecific uptake in the lymph nodes (52.2% vs. 28.3%; p: < 0.001), bones (71.7% vs. 23.9%; p < 0.001) and ganglia (71.7% vs. 43.5%; p < 0.001). Probable unspecific, exclusively [18F]-F-PSMA-1007-positive lesions mainly occurred in the ribs (58.7%), axillary lymph nodes (39.1%) and cervical ganglia (28.3%). CONCLUSION: In terms of miTNM staging, both tracers appeared widely exchangeable, as no tracer relevantly outperformed the other. The differences between the two tracers were far more common in presumable unspecific lesions than in malignant spots. A routinely performed two-tracer study could not be shown to be superior. Since it seems at least challenging for most nuclear medicine departments to provide both [18F]-F-PSMA-1007 and [68Ga]-Ga-PSMA-11, it appears reasonable to choose the PSMA radiotracer depending on local availability with attention to the greater occurrence of nonspecific bone findings with [18F]-F-PSMA-1007.

Spleno-aortic radiodensity ratio - A distinctive imaging feature to predict short-term outcome in critical care unit.

INTRODUCTION: To investigate the value of contrast-enhanced CT findings - splenic and aortic radiodensities and their ratios (spleno-aortic ratio) - in predicting the prognosis of critical care unit patients (CCU). METHODS: One hundred thirteen continuous CCU patients with an acute deterioration (Group A: 37 women, age: 67.2 ± 14.0 years) were included in the retrospective study. Radiodensities of the spleen and aorta were evaluated by two radiologists separately. The spleno-aortic ratio was calculated. Matthews correlation coefficient (MCC) was used in conjunction with receiver operating characteristic analysis (ROC) to assess if and which parameter was most suitable for short-term mortality prediction. The intra-class correlation coefficient assessed consensus across readers. To validate the results for the best predictor, a second cohort was evaluated (Group B: 354 CT scans). RESULTS: The portal venous spleno-aortic ratio was best suited to predict 72-hour mortality (AUC = 0.91). A threshold ratio ≤0.53 predicted short-term mortality with a high sensitivity (80.95%) and specificity (96.74%, MCC = 0.79). The post-test probability was 85%, assuming a pre-test probability of 18.6% (72-hour mortality rate). ICCs of HU measurements in the aorta, spleen, and its ratios showed high interrater agreement (ICC: 0.92-0.99). In a control cohort, a threshold ratio ≤0.53 predicted CCU patients outcome satisfactorily (SENS = 83.93%, SPEC = 97.65%, PPV = 87.00%, NPV = 97.00%). CONCLUSIONS: The portal venous spleno-aortic ratio serves as a distinctive imaging feature to predict short-term mortality. For CCU patients with a cut-off portal venous spleno-aortic ratio ≤0.53, the risk of dying within three days after CT scan is approximately twenty times higher.

Diagnostic performance of 18F-fluorodeoxyglucose-PET/MRI versus MRI alone in the diagnosis of pelvic recurrence of rectal cancer.

PURPOSE: To compare the diagnostic performance of 18F-fluorodeoxyglucose-PET/MRI and MRI in the diagnosis of pelvic recurrence of rectal cancer. METHODS: All PET/MRIs of patients in the follow-up of rectal cancer performed between 2011 and 2018 at our institution were retrospectively reviewed. Recurrence was confirmed/excluded either by histopathology or imaging follow-up (> 4 months). Four groups of readers (groups 1/2: one radiologist each, groups 3/4: one radiologist/one nuclear medicine physician) independently interpreted MRI and PET/MRI. The likelihood of recurrence was scored on a 5-point-scale. Inter-reader agreement, sensitivity, specificity, PPV/NPV and accuracy were assessed. ROC curve analyses were performed. RESULTS: Fourty-one PET/MRIs of 40 patients (mean 61 years ± 10.9; 11 women, 29 men) were included. Sensitivity of PET/MRI in detecting recurrence was 94%, specificity 88%, PPV/NPV 97% and 78%, accuracy 93%. Sensitivity of MRI was 88%, specificity 75%, PPV/NPV 94% and 60%, accuracy 85%. ROC curve analyses showed an AUC of 0.97 for PET/MRI and 0.92 for MRI, but the difference was not statistically significant (p = 0.116). On MRI more cases were scored as equivocal (12% versus 5%). Inter-reader agreement was substantial for PET/MRI and MRI (0.723 and 0.656, respectively). CONCLUSION: 18F-FDG-PET/MRI and MRI are accurate in the diagnosis of locally recurrent rectal cancer. Sensitivity, specificity, PPV, NPV and accuracy are comparable for both modalities, but PET/MRI increases readers' confidence levels and reduces the number of equivocal cases.

Comparison of 6-[18F]FDOPA PET with Nigrosome 1 detection in patients with parkinsonism.

BACKGROUND: The functional 6-[18F]FDOPA positron emission tomography (PET) can be a helpful tool in differentiating parkinsonism with dopaminergic deficiency from clinically similar differential diagnoses. Furthermore, in T2*/susceptibility-weighted imaging (SWI) magnetic resonance imaging (MRI) sequences the structural integrity of the Nigrosome 1 (N1) can be assessed by checking the presence of the swallow tail sign (STS). We therefore retrospectively compared the performance of the 6-[18F]FDOPA PET with the N1 detection in patients suspected with parkinsonian diseases. Forty-three consecutive patients (m: 23, f: 20, mean age: 63 ± 12 years) were included in the study. They underwent clinically indicated 6-[18F]FDOPA PET/MRI scans as part of their neurological evaluation of uncertain parkinsonian syndromes. Visual and semi-quantitative PET imaging results were statistically compared with visual N1 assessment on 3 T SWI. As the gold standard, we defined the clinical diagnosis at the last follow-up, which included idiopathic Parkinson syndrome (IPS; n = 18), atypical parkinsonian syndromes (APS; n = 9) and other neurological diseases without dopaminergic deficit (n = 16). RESULTS: Thirty-five of 43 patients (81%, Kappa 0.611) had corresponding results in 6-[18F]FDOPA PET and SWI. Seven of the remaining 8 patients were correctly diagnosed by 6-[18F]FDOPA PET alone. Sensitivity, specificity and accuracy for 6-[18F]FDOPA and N1 imaging were 93%, 94%, 93% and 82%, 75%, 79%, respectively. CONCLUSIONS: 6-[18F]FDOPA PET and Nigrosome 1 evaluation had an overall good intermodality agreement. Diagnostic agreement was very good in cases of clinically suspected idiopathic Parkinson syndrome and fair in atypical parkinsonian syndromes, but poor in patients with non-parkinsonian disorders. 6-[18F]FDOPA PET showed higher sensitivity, specificity and accuracy in discriminating parkinsonian syndromes from non-parkinsonian disorders than the N1 evaluation. In summary, the additional benefit of N1 assessment in patients with APS or parkinsonism without dopaminergic deficit needs to be proven by prospective studies.

Adrenal glands enhancement in computed tomography as predictor of short-and intermediate term mortality in critically ill patients.

PURPOSE: To investigate whether adrenal gland radiodensities alone or compared to the inferior vena cava (IVC) can correctly predict hospital mortality in patients in intensive care. METHODS: One hundred thirteen intensive care patients (76 males, age: 67.2 ± 14.0 years) with an acute clinical deterioration were included in this retrospective analysis. For the venous and the arterial phase CT attenuation (Hounsfield units) of adrenal glands and IVC was ROI-based evaluated by two radiologists separately. ROC analysis, combined with the Matthews Correlation Coefficient (MCC) as a classifier, was used to assess whether one of the parameters is suitable for predicting short and medium-term mortality and, if so, which parameter is most appropriate. Interrater agreement was assessed using the intraclass correlation coefficient. RESULTS: Twenty-one patients (18.6%) died within three days in the ICU. Measurements of the adrenal glands in the portal venous phase yielded the highest discriminative power (=AUC) to distinguish between deceased and survivors. A threshold ratio of >95.5 predicted 72-hour mortality with a sensitivity of 76.19% and a specificity of 92.39% (AUC = 0.84; p < 0.0001). The positive likelihood ratio was 10.1; the positive predictive value was 69%. The predictive power for 24-hour mortality was slightly lower. Venous adrenal-to-IVC ratios and arterial measurements as a whole were substantially less suitable. All intraclass correlation coefficients indicated a high interrater agreement. CONCLUSIONS: In the portal venous phase, hyperattenuating of the adrenal glands on contrast-enhanced CT can predict short and intermediate ICU mortality quite well and may serve as a reproducible prognostic marker for individual patient outcomes.

Bilateral adrenal enhancement revised-adrenal-to-spleen ratio as an appropriate mortality predictor.

PURPOSE: To investigate whether adrenal gland radiodensities alone or set in relation to either the inferior vena cava (IVC) or the spleen can predict hospital mortality in intensive care unit patients. METHODS: One hundred thirty-three intensive care patients (90 males, age: 66.3 ± 14.5 years) with an acute clinical deterioration were included in this retrospective analysis. CT attenuation (Hounsfield units) of adrenal glands, IVC, and spleen was evaluated by 2 radiologists separately. Adrenal-to-IVC and adrenal-to-spleen ratios were calculated. Receiver operating characteristic (ROC) analysis, combined with the Matthews correlation coefficient (MCC) as a classifier, was used to assess which parameter is the most suitable for short-term, intermediate-term, and overall mortality prediction. Interrater agreement was assessed using intraclass correlation coefficient (ICC). RESULTS: The highest discriminative power to distinguish between deceased and survivors was found for the adrenal gland-to-spleen ratio for the 72-h mortality. A threshold of > 1.4 predicted 72-h mortality with a sensitivity of 79.31% and a specificity of 98.08% (area und the curve (AUC) = 0.94; p < 0.0001; MCCs = 0.81). The positive likelihood ratio was 41; the positive predictive value was 92.20%. Adrenal gland-to-spleen ratio was also best suited to predict the 24-h and overall mortality. ICCs of HU measurements in adrenal gland, IVC, and spleen indicated a high interrater agreement (ICC 0.95-0.99). CONCLUSIONS: To conclude, the adrenal-to-spleen ratio in CT in portal venous phase may serve as an imaged-based predictor for short, intermediate, and overall mortality and as reproducible prognostic marker for patient outcome.

Rapidly Evolving Diffuse Omental Carcinomatosis of Prostate Cancer in 68Ga-PSMA PET/CT.

ABSTRACT: An 81-year-old man received androgen deprivation therapy for a locally advanced prostate cancer and, 6 months later, a curative radiation therapy. Half a year later, the patient presented with a steeply increased PSA value (32 ng/mL) and a suppressed testosterone level (0.48 nmol/L). The consecutively performed 68Ga-PSMA PET/CT revealed, besides local tumor remains and several PSMA-positive lymph node and soft tissue metastases, an extensive, diffuse PSMA ligand accumulation in the omentum, which was immunohistochemically proven to be a carcinomatosis of prostate cancer. None of the extraprostatic lesions were present in the pretherapeutic PSMA PET 1 year ago.

[68Ga]Ga-PSMA-11 PET before and after initial long-term androgen deprivation in patients with newly diagnosed prostate cancer: a retrospective single-center study.

PURPOSE: The study aimed to evaluate the effect of androgen deprivation therapy (ADT) on PSMA imaging and its correlation to the PSA concentration by comparing qualitative and quantitative parameters: SUVmax, SUVmean, PSMA-derived tumor volume (PSMA-TV), total lesion PSMA (TL-PSMA) and molecular imaging (mi)PSMA score. METHODS: Retrospective analysis of 21 therapy-naïve patients with oligometastatic prostate cancer (median age 70 years) who underwent either [68Ga]Ga-PSMA-11-PET/CT or -PET/MRI before initiation of (T1) as well as during ADT (T2). The median duration of ADT was 155 days (range 61-289 days). All lesions were analyzed using several qualitative and quantitative PET parameters. RESULTS: A total of 109 PSMA-positive lesions (24 intraprostatic, 56 lymphonodal and 29 osseous) were visually detected at any of the examinations, while at T2, two new bone lesions were detected in one patient. During ADT, all patients experienced a decrease in their PSA level (median: 29.1 before vs. 0.71 after; p < 0.001). During long-term ADT, a relevant decrease in lesion count occurred, especially in patients with a T2 PSA value < 1 ng/ml (median: 4 vs. 0.9; p = 0.007) and PSMA expression, which resulted in miN- and/or miM-downstaging in 11 patients (52.7%). All analyzed PET parameters correlated strongly with each other. The PSA level at T2 correlated modestly with the decrease in PSMA expression and its derived volumes. CONCLUSION: Post-ADT scans detected, especially in patients with a residual PSA < 1 ng/ml, fewer PSMA-positive lesions with overall lower PSMA expression, regardless of primary tumor site or metastatic sites. None of the PET parameters has proven to be superior, as they all correlated modestly with the PSA value at T2. Thus, the simply acquirable miPSMA score seems to be the most suitable for evaluating the effect of ADT on PSMA expression.

Tracking a TGF-ß activator in vivo: sensitive PET imaging of αvß8-integrin with the Ga-68-labeled cyclic RGD octapeptide trimer Ga-68-Triveoctin.

PURPOSE: As a major activator of transforming growth factor ß (TGF-ß), the RGD receptor αvß8-integrin is involved in pathogenic processes related to TGF-ß dysregulation, such as tumor growth, invasion, and radiochemoresistance, metastasis and tumor cell stemness, as well as epithelial-mesenchymal transition. The novel positron emission tomography (PET) radiopharmaceutical Ga-68-Triveoctin for in vivo mapping of αvß8-integrin expression might enhance the prognosis of certain tumor entities, as well as support and augment TGF-ß-targeted therapeutic approaches. METHODS: Monomeric and trimeric conjugates of cyclo(GLRGDLp(NMe)K(pent-4-ynoic amide)) were synthesized by click chemistry (CuAAC), labeled with Ga-68, and evaluated in MeWo (human melanoma) xenografted SCID mice by means of PET and ex-vivo biodistribution. αvß8-integrin expression in murine tissues was determined by ß8-IHC. A human subject received a single injection of 173 MBq of Ga-68-Triveoctin and underwent 3 subsequent PET/CT scans at 25, 45, and 90 min p.i.. RESULTS: The trimer Ga-68-Triveoctin exhibits a 6.7-fold higher αvß8-integrin affinity than the monomer (IC50 of 5.7 vs. 38 nM, respectively). Accordingly, biodistribution showed a higher tumor uptake (1.9 vs. 1.0%IA/g, respectively) but a similar baseline upon blockade (0.25%IA/g for both). IHC showed an intermediate ß8-expression in the tumor while most organs and tissues were found ß8-negative. Low non-target tissue uptakes (< 0.4%IA/g) confirmed a low degree of unspecific binding. Due to its hydrophilicity (log D = - 3.1), Ga-68-Triveoctin is excreted renally and shows favorable tumor/tissue ratios in mice (t/blood: 6.7; t/liver: 6.8; t/muscle: 29). A high kidney uptake in mice (kidney-to-blood and -to-muscle ratios of 126 and 505, respectively) is not reflected by human PET (corresponding values are 15 and 30, respectively), which furthermore showed notable uptakes in coeliac and choroid plexus (SUVmean 6.1 and 9.7, respectively, 90 min p.i.). CONCLUSION: Ga-68-Triveoctin enables sensitive in-vivo imaging αvß8-integrin expression in murine tumor xenografts. PET in a human subject confirmed a favorable biodistribution, underscoring the potential of Ga-68-Triveoctin for mapping of αvß8-integrin expression in a clinical setting.

Vascular changes of the superior mesenteric artery (SMA): A new component of the hypovolemic shock complex (HSC).

PURPOSE: To assess the type and frequency of vascular changes in the superior mesenteric artery (SMA) associated with the hypovolemic shock complex (HSC). METHODS: Twenty-six patients (14 males, 70.6 ±â€¯11.2 years) meeting the criteria for hypovolemic shock complex in computed tomography were examined for the presence of angiographic signs of non-occlusive mesenteric ischemia (NOMI) in the SMA: the string of sausages sign and spasms of the arcades of mesenteric arteries on coronal maximum intensity projection images (MIP). Interrater agreement was assessed using weighted kappa (κ). RESULTS: Vascular changes of the SMA were visible in almost all of the patients with HSC with a frequency of 88.5 %-96.2 %. Intraclass correlation coefficients indicated a substantial to almost perfect interrater agreement. CONCLUSIONS: Using computed tomography, it is possible to reliably and reproducibly detect vascular changes in SMA known from angiography in the context of hypoperfusion. The pathological vascular changes also occur more frequently than other classic signs of a CT hypoperfusion complex. Since the qualitative assessment of the SMA requires only a small amount of time, it is suitable as a further criterion for the presence of the CT hypoperfusion complex.

Hepatic Vascular Malformation Mimics PSMA-Positive Prostate Cancer Metastasis.

An 80-year-old man developed high-risk prostate cancer after 7 years of active surveillance. For staging and treatment planning, a Ga-PSMA PET/MRI was performed. Besides the PSMA-positive primary tumor and a solitary bone metastasis in the fifth thoracic vertebral body, an intensive intrahepatic PSMA expression (SUVmax, 16.3) was suspicious for a liver metastasis. The results of a previously performed contrast-enhanced CT, a consecutively performed contrast-enhanced ultrasound, and a follow-up PSMA PET/CT after 4 months with a stable lesion during androgen deprivation lead to the diagnosis of a vascular malformation metabolically mimicking a hepatic metastasis of the prostate tumor.

Diffusion-weighted MRI for initial staging in Hodgkin`s lymphoma: comparison with FDG PET.

PURPOSE: To evaluate the use of diffusion-weighted MRI (DWI) for initial staging of Hodgkin`s lymphoma and compare it to FDG PET. METHODS: Forty-one patients with Hodgkin`s lymphoma (14 f, 27 m, median age 39 y) were included in this retrospective study. All patients underwent FDG PET/MR for initial staging, including DWI. The Lugano classification was used to describe disease extent. A combination of follow-up imaging and histopathology served as the reference standard. Method agreement was assessed using weighted kappa (κ). The accuracy of the imaging methods was evaluated using ROC curve analysis. RESULTS: Regarding the Lugano stage, DWI and FDG PET had identical results in 34/41 cases (κ = 0.77). Sensitivity and specificity for nodal involvement was 89.9% and 93.8% for DWI, and 93.8% and 86.9% for FDG PET, respectively. In regard to extranodal involvement, sensitivity and specificity were 88.5% and 99.3% for DWI and 92.3% and 92.7% for FDG PET. The accuracy of both methods for nodal (p = 0.06) and extranodal involvement (p = 0.66) did not differ significantly. CONCLUSION: Despite high sensitivity and specificity, DWI in free breathing cannot be currently recommended as an alternative to FDG PET in initial staging of Hodgkin`s lymphoma due to substantial differences in regard to therapy-determining Lugano Stage.

68Ga-RM2 PET in PSMA- positive and -negative prostate cancer patients.

AIM: 68Ga-PSMA-11 is the gold standard for molecular imaging of prostate cancer. However, recurrent tumor manifestations or metastases cannot be detected in every case. Therefore, we investigated if there is an additive value of the gastrin-releasing peptide receptor (GRP-R) ligand 68Ga-RM2 compared to the well-established 68Ga-PSMA-11 in patients with (Group 1) and without (Group 2) pathologic PSMA-expression in different tumor stages. PATIENTS AND METHODS: Sixteen men (median age: 74 years, range 50-80 years) with prostate cancer in different stages who had a recent negative (n = 8) or pathologic (n = 8) PSMA PET underwent a subsequent 68Ga-RM2 PET. Both examinations were analyzed qualitatively and quantitatively and compared in terms of pathologic and physiologic tracer distribution. RESULTS: None of the PSMA-negative patients showed any pathological RM2-accumulation. Pathologic PSMA-uptake was observed in 8 patients of whom 5 had pathologic RM2-uptake. The number of patients with a local recurrence was equal in both scans (n = 3). Bone metastases and lymph node metastases were detected in less patients in RM2 PET compared to PSMA PET (n = 4 vs. 7 and n = 2 vs. 5, respectively). In one patient, PSMA-positive liver metastases were not detected in RM2. RM2 PET revealed two additional lesions indicative for bone metastases in two patients with multiple PSMA-positive bone metastases, which had no therapeutic consequence. CONCLUSION: At least in our small and heterogeneous patient population, 68Ga-RM2 showed no clinically relevant, additional benefit compared to 68Ga-PSMA-11 PET.

Diagnosis of Huntington's disease via sequential 18F-DOPA and 18F-FDG PET/MRI.

Cases of rare movement disorders like Huntington's disease (HD) are not easy to diagnose, especially when occurring sporadically, without documented family history. In HD patients, MRI scans commonly feature atrophy of the striatum and reduced volume of white matter. But if morphological findings remain unspecific, functional PET imaging could provide valuable information to further clarify diagnosis. We present a case report of a 56-year-old woman suffering from mild hypokinetic-rigid syndrome and depression, suspicious of Parkinson's disease, who was referred to 18F-DOPA and 18F-FDG PET/MRI scans at our department.

Dual-time-point 64 Cu-PSMA-617-PET/CT in patients suffering from prostate cancer.

Regardless of its high positron energy, 68 Ga-labeled PSMA ligands have become standard of care in metabolic prostate cancer imaging. 64 Cu, a radionuclide with a much longer half-life (12.7 h), is available for PSMA labeling allowing imaging much later than 68 Ga. In this study, the diagnostic performance of 64 Cu-labeled PSMA was compared between early and late scans. Sixteen men (median age: 70 y) with prostate cancer in different stages underwent 64 Cu-PSMA-617-PET/CT 2 and 22 hours post tracer injection. Pathologic and physiologic uptakes were analyzed for both points of time. Pathologic tracer accumulations occurred in 12 patients. Five patients presented with pathologic uptake in 17 different lymph nodes, two patients showed pathologic bone uptake in nine lesions, and seven patients had pathologic PSMA uptake in eight prostatic lesions. Physiologic uptake of the renal parenchyma, urine bladder, and salivary glands decreased over time, while the physiologic uptake of liver and bowel increased. In the present study, 64 Cu-PSMA-617-PET demonstrated to be feasible for imaging prostate cancer for both the primary tumor site and metastases. Later imaging showed no additional, clinically relevant benefit compared with the early scans. At least the investigated time points we chose did not vindicate the additional expenditure.