Biomarkers sensitive to functional impairment, neuronal loss, tau, and amyloid pathology based on MR, PET, and CSF studies are increasingly used to diagnose Alzheimer's disease (AD), but clinical validation is incomplete, hampering reimbursement by payers, widespread clinical implementation, and impacting on health care quality. An expert group convened to develop a strategic research agenda to foster the clinical validation of AD biomarkers. These demonstrated sufficient evidence of analytical validity (phase I of a structured framework adapted from oncology). Research priorities were identified based on incomplete clinical validity (phases II and III), and clinical utility (phases IV and V). Priorities included: definition of the assays; reading procedures and thresholds for normality; performance in detecting early disease; accounting for the effect of covariates; diagnostic algorithms comprising combinations of biomarkers; and developing best practice guidelines for the use of biomarkers in qualified memory clinics in the context of phase IV studies. 5 GlossaryBiomarker. An objective measure of a biological or pathogenic process with the purpose of evaluating disease risk or prognosis, guiding clinical diagnosis or monitoring therapeutic interventions. While the term originally referred to traceable substances produced by or introduced into an organism, it later evolved to any measurable parameter, including those obtained via imaging procedures.Roadmap. Objective-oriented, structured, and efficient action plan. In science and technology also called "strategic research agenda".Alzheimer's disease (AD) dementia. Traditionally and according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria, Alzheimer's disease was defined as a syndrome with progressive cognitive impairment severe enough to impact on daily activities. A diagnosis of Alzheimer's disease could only be made after exclusion of other possible causes. 1 Sixty-five to 80% of cases of patients fulfilling these criteria have Alzheimer's pathology (plaques and tangles), the remainder having a range of other pathologies. In order to increase diagnostic certainty, contemporary criteria for AD dementia incorporate biomarker evidence for different aspects of Alzheimer's pathology, including imaging (magnetic resonance imaging -MRI -measures of atrophy; 18 F-fluorodeoxyglucose-positron emission tomography -FDG-PET -measures of cerebral hypometabolism; amyloid PET measures of fibrillar β-amyloid -A -deposition) and cerebrospinal fluid -CSF (decreased levels of A42, increased levels of tau and phospho-tau). 2,3 Alzheimer's disease process. Recognizing that AD pathology is present many years before symptoms emerge, new criteria classify the disease process on a continuum from asymptomatic to prodromal and finally to dementia stage. 4 Individuals at the asymptomatic stage can only be identified by biomarkers of Alzheimer's pathology. None...

Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH (Ga-RM2) is a synthetic bombesin receptor antagonist that targets gastrin-releasing peptide receptor (GRPr). GRPr proteins are highly overexpressed in several human tumors, including prostate cancer (PCa). We present data from the use of Ga-RM2 in patients with biochemical recurrence (BCR) of PCa and negative findings on conventional imaging. We enrolled 32 men with BCR of PCa, who were 59-83 y old (mean ± SD, 68.7 ± 6.4 y). Imaging started at 40-69 min (mean, 50.5 ± 6.8 min) after injection of 133.2-151.7 MBq (mean, 140.6 ± 7.4 MBq) of Ga-RM2 using a time-of-flight-enabled simultaneous PET/MRI scanner. T1-weighted, T2-weighted, and diffusion-weighted images were acquired. All patients had a rising level of prostate-specific antigen (PSA) (range, 0.3-119.0 ng/mL; mean, 10.1 ± 21.3 ng/mL) and negative findings on conventional imaging (CT or MRI, and a Tc-methylene diphosphonate bone scan) before enrollment. The observedGa-RM2 PET detection rate was 71.8%. Ga-RM2 PET identified recurrent PCa in 23 of the 32 participants, whereas the simultaneous MRI scan identified findings compatible with recurrent PCa in 11 of the 32 patients. PSA velocity was 0.32 ± 0.59 ng/mL/y (range, 0.04-1.9 ng/mL/y) in patients with negative PET findings and 2.51 ± 2.16 ng/mL/y (range, 0.13-8.68 ng/mL/y) in patients with positive PET findings ( = 0.006). Ga-RM2 PET can be used for assessment of GRPr expression in patients with BCR of PCa. High uptake in multiple areas compatible with cancer lesions suggests thatGa-RM2 is a promising PET radiopharmaceutical for localization of disease in patients with BCR of PCa and negative findings on conventional imaging.

HighlightsElevated tau PET signal was seen in a subset of patients at risk for CTE.Highest tracer retention was found in patients with positive amyloid PET.Tau PET, FDG and MRI showed converging abnormalities in frontotemporal regions.

The impact of prostate specific membrane antigen (PSMA) PET/CT on management of prostate cancer (PCa) patients with biochemical recurrence (BCR) is well-established. However, whether and how PSMA PET/CT affects the management of patients undergoing scans for other clinical indications remains unknown. The goal of this study was to determine the impact of 68 Ga-PSMA-11 PET/CT on initial and subsequent management decisions in a cohort of PCa patients referred for various indications ("basket trial") excluding the two main classical indications: BCR and presurgical staging. Methods: This was a prospective study of 197 patients that aimed to determine the impact of 68 Ga-PSMA-11 PET/CT on PCa stage and management. Indications for PSMA PET/CT were: initial staging of non-surgical candidates (30 patients) and re-staging after definitive treatment (n=168). The re-staging cohort comprised: patients re-staged with known advanced metastatic disease (n=103), after androgen deprivation therapy only (n=16), after surgery with serum PSA levels <0.2 ng/ml (n=13), after radiation therapy (RT) not meeting the Phoenix criteria (n=22) and after other primary local treatments [i.e. high-intensity focused ultrasound (HIFU), focal laser ablation, cryoablation, hyperthermia or irreversible electroporation] (n=13). Patients with BCR and candidates for curative surgery were excluded. Impact on management was assessed using pre-and post-PET questionnaires completed by referring physicians, electronic chart review and/or patient telephone encounters. Results: PSMA PET/CT changed disease stage in 135/197 (69%) patients (38% up-stage, 30% down-stage and no changes in stage in 32%). Management was affected in 104/182 (57%) patients. Specifically, PSMA PET/CT impacted management of patients who were re-staged after RT

BackgroundA newly introduced PET/CT scanner (Discovery Meaningful Insights—DMI, GE Healthcare) includes the silicon photomultiplier (SiPM) with time-of-flight (TOF) technology first used in the GE SIGNA PET/MRI. In this study, we investigated the impact of various acquisition times on image quality using this SiPM-based PET/CT.MethodsWe reviewed data from 58 participants with cancer who were scanned using the DMI PET/CT scanner. The administered dosages ranged 295.3–429.9 MBq (mean ± SD 356.3 ± 37.4) and imaging started at 71–142 min (mean ± SD 101.41 ± 17.52) after administration of the radiopharmaceutical. The patients’ BMI ranged 19.79–46.16 (mean ± SD 26.55 ± 5.53). We retrospectively reconstructed the raw TOF data at 30, 60, 90, and 120 s/bed and at the standard image acquisition time per clinical protocol (180 or 210 s/bed depending on BMI). Each reconstruction was reviewed blindly by two nuclear medicine physicians and scored 1–5 (1—poor, 5—excellent quality). The liver signal-to-noise ratio (SNR) was used as a quantitative measure of image quality.ResultsThe average scores ± SD of the readers were 2.61 ± 0.83, 3.70 ± 0.92, 4.36 ± 0.82, 4.82 ± 0.39, and 4.91 ± 0.91 for the 30, 60, 90, and 120 s/bed and at standard acquisition time, respectively. Inter-reader agreement on image quality assessment was good, with a weighted kappa of 0.80 (95% CI 0.72–0.81). In the evaluation of the effects of time per bed acquisition on semi-quantitative measurements, we found that the only time point significantly different from the standard time were 30 and 60 s (both with P < 0.001). The effects of dose and BMI were not statistically significant (P = 0.195 and 0.098, respectively). There was a significant positive effect of time on SNR (P < 0.001), as well as a significant negative effect of weight (P < 0.001).ConclusionsOur results suggest that despite significant delays from injection to imaging (due to comparison with standard PET/CT) compared to standard clinical operations and even in a population with average BMI > 25, images can be acquired as fast as 90 s/bed using the SiPM PET/CT and still result in very good image quality (average score > 4).

In this article, we provide an overview of established and emerging conventional nuclear medicine and PET imaging biomarkers, as the diagnostic nuclear medicine portfolio is rapidly expanding. Next, we review briefly nuclear theranostic approaches that have already entered or are about to enter clinical routine. Using some approximations and taking into account emerging applications, we also provide some simplified business forecasts for nuclear theranostics. We argue that an optimistic outlook by the nuclear medicine community is crucial to the growth of the specialty and emphasize the urgent need for training adaptations.

The role of prostate-specific membrane antigen (PSMA)-targeted PET in comparison to mpMRI in the evaluation of intraprostatic cancer foci is not well defined. The aim of our study was to compare the diagnostic performances of PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI using 3 independent blinded readers for each modality and with histopathology as gold standard in the detection, intra-prostatic localization and local extension of primary prostate cancer.Methods: Patients with intermediate-or high-risk prostate cancer who underwent a PSMA PET/CT as part of the prospective trial (NCT03368547) and a mpMRI prior to radical prostatectomy were included. Each imaging modality was interpreted by 3 blinded independent readers unaware of the other modality result. Central majority rule was applied (2:1). Whole-mount pathology was used as the gold-standard. Imaging scans and whole-mount pathology were interpreted using the same standardized approach on a segment-and lesion-level. A "neighboring" approach was used to define imaging/pathology correlation for the detection of individual prostate cancer foci. Accuracy in determining the location, extraprostatic extension (EPE) and seminal vesicle invasion (SVI) of prostate cancer foci was assessed using receiver operating characteristic (ROC) analysis. Inter-reader agreement was calculated using inter-class coefficient (ICC) analysis. Results:The final analysis included 74 patients (14/74 -19%) intermediate risk and 60/74 -81%) high risk). Cancer detection rate (lesion-based analysis) was 85%, 83% and 87 for PSMA PET/CT, mpMRI and PSMA PET/CT+mpMRI, respectively. ΔAUC between PSMA PET/CT+mpMRI and the two imaging modalities alone for delineation of tumor localization (segment-based analysis) was statistically significant (p<0.001), but not between PSMA PET/CT and mpMRI (p=0.093). mpMRI outperformed PSMA PET/CT in detecting EPE (p=0.002) and SVI (p=0.001). On a segment-level analysis, ICC analysis showed moderate reliability among PSMA PET/CT and mpMRI readers using a 5-point Likert scale (range: 0.53 to 0.64). In the evaluation of T-staging, poor reliability was found among PSMA PET/CT readers and poor to moderate reliability was found for mpMRI readers. Conclusions: PSMA PET/CT and mpMRI have similar accuracy in the detection and intra-prostatic localization of prostate cancer foci. mpMRI performs better in identifying EPE and SVI. For the T-staging evaluation of intermediate to high-risk prostate cancer patients, mpMRI should still be considered the imaging modality of reference. Whenever available, PSMA PET/MRI or the co-registration/fusion of PSMA PET/CT and mpMRI (PSMA PET+mpMRI) should be used as it improves tumor extent delineation.

nortropane ( 18 F-FE-PE2I) is a newly developed dopamine transporter (DAT) PET radioligand. Full quantification methods rely on dynamic acquisition of 18 F-FE-PE2I, but in a clinical setting a simplified protocol is preferable. The aims of this study were to identify the optimal acquisition time window for 18 F-FE-PE2I and to validate the specific binding ratio (SBR) as a simplified quantification method. Methods: Ten Parkinson disease (PD) patients and 10 controls were included. Ninety-three-min dynamic PET measurements with 18 F-FE-PE2I were conducted using the high-resolution research tomograph (HRRT). The dynamic measurement was also smoothed to the resolution of a clinical PET system (HR). Regions of interest for the caudate, putamen, ventral striatum, substantia nigra (SN), and cerebellum were manually drawn on coregistered MR images. The outcome measure was the SBR, and the gold standard was the binding potential obtained with wavelet-aided parametric imaging (WAPI BP ND ). The cerebellum was used as a reference region. In a preliminary analysis, SBR was computed for 8 time windows (SBR dyn ). Linear regression analysis and Bland-Altman plots were used to select the optimal acquisition time window. An average image from the selected time window was created, from which new SBR values (SBR calculated on the average image on the HRRT and SBR calculated on the average image on the simulated HR images) were calculated and compared with WAPI BP ND . The effect size was calculated. Results: SBR dyn values for the time window between 16.5 and 42 min correlated best with WAPI BP ND (r 2 5 0.98, P , 0.001). Significant correlations (P , 0.001) were observed between SBR HR and WAPI-BP ND (r 2 5 0.95 in controls and 0.97 in PD patients). In the striatum, SBR HR values were 37% lower than BP ND in controls, 29% in PD patients, whereas in the SN the underestimation was 22% in controls and 15% in PD patients. Similar effect sizes for BP ND and SBR HR were found in the caudate (0.6), putamen (1.7 and 1.4), ventral striatum (0.7), and SN (0.5 and 0.4). Conclusion: A single 18 F-FE-PE2I acquisition between 16.5 and 42 min provides the best outcome measure for simplified DAT quantification. Despite underestimation of the BP ND , the SBR can be used in a clinical setting as a valid quantification method for DAT using 18 F-FE-PE2I, because it provides differentiation similar to BP ND between controls and PD patients. The dopaminergic system has a crucial role in the pathogenesis of several psychiatric and neurodegenerative diseases (1-6) and has been the focus of research for decades. The link between dopaminergic degeneration and the pathophysiology of motor symptoms in Parkinson disease (PD) has been known for more than a century (7), and despite this acquired knowledge the dopaminergic system is still an active field of research.The dopamine transporter (DAT), a presynaptic membrane protein responsible for dopamine reuptake, plays a key role in regulating the intensity and duration of the dopaminergic neurotransmission (8,...