Investigations of possible links between Alzheimer’s disease and type 2 diabetes mellitus by positron emission tomography: a systematic review Abstract Purpose To review published evidence of possible links between Alzheimer’s disease (AD) and type-2 diabetes mellitus revealed by positron emission tomography (PET). Methods We searched online databases with keywords diabetes mellitus (DM), AD, and PET. We assessed the studies in terms of purpose, methodology, materials, and relationships between AD and DM suggested by PET imaging. Results After removal of 142 duplicates, 227 hits yielded no more than 15 full-length publications, from which we excluded six for specific reasons. The remaining nine studies were not directly comparable because of differences of purpose, study design, material, and methods. Individual subject materials consisted of 4–154 patients in case–control (4), observational (4), and longitudinal (1) studies, the last including only four DM patients. Mean patient age was 76.4 years (range 45–90). In five studies, researchers examined regional cerebral glucose metabolism with 18F-fluorodeoxyglucose (FDG), in three studies, researchers imaged amyloid with PET, and in one study, they measured both glucose metabolism and amyloid deposition. All four studies of amyloid tracers led to the conclusion that amyloid deposition was unaffected by DM status. Evidence of insulin resistance and increased blood glucose was associated with decreased FDG accumulation in AD signature regions in DM patients. Conclusion The relationships between DM and AD identified by PET appear to be independent of amyloid deposition and predominantly highlighted by reduced glucose metabolism, as suggested by four of the five glucose metabolism studies.

The eye of nuclear medicine

PET imaging of vulnerable coronary artery plaques Abstract Purpose In the last years, the identification of vulnerable atherosclerotic plaques to prevent acute coronary events has been one of the main objectives of the cardiovascular science community. In this review, we provide an overview of vulnerable coronary artery plaque imaging by positron emission tomography (PET). Methods and results Relevant methodological and technical aspects of PET on coronary artery plaque imaging are first analysed. Second, the main radiotracers used in this area as well as the main results of the clinical studies published so far are described. From published data, specialized approaches are recommended for imaging protocol and quantitative analysis of plaque activity. 18F-fluorodeoxyglucose (18F-FDG), the first radiotracer used for its wide availability, has several limitations for the detection and quantification of coronary artery plaque inflammation. 18F-sodium fluoride (18F-NaF), a marker of vascular microcalcification, seems to be the most promising radiotracer for vulnerable coronary artery plaque imaging. 68Ga-DOTATATE and 68Ga-pentixafor have also shown interesting results on coronary plaque inflammation in humans. Data on coronary imaging in humans are lacking for other radiotracers that target inflammation, hypoxia and neoangiogenesis. Conclusions Molecular imaging by PET is a powerful tool for imaging different components of vulnerable coronary artery plaques and, potentially, for selecting patients at high-risk of myocardial infarction for personalized treatments. However, the results of large clinical trials on asymptomatic patients to link coronary plaque activity to patient outcome are strongly required.

Targeting prostate cancer with the anti-PSMA scFvD2B: a theranostic promise for nuclear medicine Abstract Introduction Despite the significant research activity in the design and validation of new PSMA-targeting agents, prostate cancer (PCa) remains the second most common cancer in men worldwide. PSMA-specific labeled monoclonal antibodies (mAbs) demonstrated a discrete effectiveness in the clinic, but with some drawbacks due to their large size. To circumvent these problems, mAbs-derived fragments have been investigated, since they retain the high affinity of the parent mAb for the target, being also endowed with a more favorable pharmacokinetics. This review focuses on the single-chain variable fragment D2B (scFvD2B) potentiality as a new prostate-specific membrane antigen (PSMA)-specific molecular vector in nuclear medicine (NM) applications for both diagnosis and treatment of PCa. Methods A critical review of PubMed and Web of Science (including MEDLINE) in the early 2019 was performed, searching for research articles focusing on the application of the fragment scFvD2B and the parent antibody IgGD2B in preclinical NM. Results The scFvD2B, which is derived from one of the most promising PSMA-specific mAbs, IgGD2B, has been recently investigated and labeled with Indium-111, Iodine-131, and Iodine-123. Overall, scFvD2B showed a great potential in the preclinical setting, demonstrating a promising pharmacokinetics, especially in terms of high stability and specificity, efficiently accumulating in PSMA-expressing PCa tumors. Conclusion scFvD2B seems to be a promising fragment as a molecular vector in NM applications. Nevertheless, further investigations, especially with radiometal-labeled scFvD2B, are necessary to better characterize and optimize the unique properties of this fragment, providing the basis for a rapid translation into the clinic.

Detection rate of radiolabelled choline PET or PET/CT in hepatocellular carcinoma: an updated systematic review and meta-analysis Abstract Background Different imaging methods have been used to detect hepatocellular carcinoma (HCC). As there are increasing literature data about the role of radiolabelled choline PET/CT in this setting, we aimed to perform an updated meta-analysis about the detection rate (DR) of this imaging method in HCC. Methods A comprehensive computer literature search of studies published through December 2018 in PubMed/MEDLINE, Embase and Cochrane library databases regarding the DR of radiolabelled choline PET or PET/CT in patients with HCC was carried out. Pooled DR were calculated on a per patient- and on a per lesion-based analysis. Subgroup analyses taking into account the radiopharmaceutical used were performed. Results Nine studies (283 HCC patients) were included in the pooled analysis. The pooled DR of radiolabelled choline PET or PET/CT on a per patient- and on a per lesion-based analysis was 83% [95% confidence interval (95% CI) 75–89%] and 79% (95% CI 72–86%), respectively. A significant heterogeneity among the studies was found on a per lesion-based analysis only. No significant publication bias was found. The subgroup analysis demonstrated a trend towards a higher DR when using 18F-choline compared to 11C-choline, without a statistically significant difference. Pooled DR of HCC using dual-tracer PET/CT (radiolabelled choline and 18F-FDG) on a per patient- and a per lesion-based analysis was 91% (95% CI 87–95%) and 89% (95% CI 80–95%), respectively, without significant heterogeneity. Conclusions Radiolabelled choline PET/CT demonstrated good ability in detecting HCC. The DR increased when dual-tracer PET/CT was performed. Large multicenter studies and cost-effectiveness analyses are warranted.

The value of yttrium-90 PET/CT after hepatic radioembolization: a pictorial essay Abstract Introduction Distribution of microspheres after radioembolization can be accurately visualized using PET/CT. In this pictorial essay, we aim to demonstrate the value of 90Y-PET/CT after radioembolization. Methods 90Y-PET/CT imaging was routinely performed after radioembolization at our institute. Patients were scanned the same day or the day after treatment, using a scanner with time-of-flight technology. We retrospectively reviewed all 90Y-PET/CTs from patients treated with radioembolization (both glass and resin microspheres) between January 2011 and January 2019. Five cases were selected that are illustrative of the added value of PET/CT after radioembolization. Results 90Y-PET/CT allows for distribution assessment and dosimetry of 90Y-microspheres. It was used for the assessment of treatment success by visualization of tumor targeting, quantification of the absorbed dose, prediction of complications such as radioembolization-induced liver disease, and determining the required dosage for retreatment. Conclusion PET/CT is an excellent modality for post-treatment imaging of 90Y-microspheres and could lead to improved dose planning and more personalized treatment.

PET biomarkers and probes for treatment response assessment in glioblastoma: a work in progress Abstract Aims Several pharmacological approaches are used for glioblastoma (GBM) treatment, each hinging on the triggering of different biochemical or functional processes; the development of specific and sensitive PET procedures for monitoring their efficacy proceeds with the identification of such new treatments. This paper presents an overview of the available “tumour biomarker”–“PET probe” pairs (i.e. the combination of a tumour target and a selective PET radiopharmaceutical) for monitoring the different treatments for GBM tested in human subjects. Methods A bibliographic search for papers on PET imaging for assessing treatment response in GBM was performed in PubMed and Web of science databases using the following string: (PET or positron) and (glioblastoma) and (treatment) and (monitoring); papers dealing with studies in human subjects published over the last 10 years were reviewed. Further papers were extracted from the bibliography of the reviewed papers. Results In this review, we highlight through a detailed table that in spite of the current use in GBM patients of a large variety of PET radiopharmaceuticals, very few papers have specifically addressed the issue of the optimization and use of imaging biomarker–probe pairs for the assessment of treatment response in GBM. While new PET probes are being developed for assessing old and new GBM biomarkers, very few clinical trials have been performed to this end. Conclusion Whereas it appears that the use of old and new PET radiopharmaceuticals can advance the non-invasive assessment of treatment response in GBM, the optimal match of biomarker–probe pairs although highly needed is still being sought in particular with the active development of new highly specific treatments characterized by novel antitumoral targeting strategies.

FDG-PET/CT as a diagnostic tool in vascular graft infection: a systematic review and meta-analysis Abstract Purpose Vascular graft infection (VGI) in central grafts is a rare but dreaded complication with a high mortality. Several imaging modalities are employed, all with pros and cons. Computed tomography is the standard, but lacks sensitivity for low-grade infections. There is still no consensus regarding the diagnostic modality of choice. The study objective was to assess the role of combined positron emission tomography and computed tomography with fluorodeoxyglucose (FDG-PET/CT) in the diagnostic workup of VGI in central grafts. Methods A systematic review was conducted according to the PRISMA guidelines through a search in Embase, PubMed, and Cochrane databases. Meta-analysis on accuracy measures was carried out with random effects models for three parameters: focal uptake, visual grading scale (VGS), and maximum standardized uptake value (SUVmax). Heterogeneity among studies was assessed with the I-squared test. Results A total of 307 studies were identified and 9 were eligible for inclusion. The pooled estimates for sensitivity and specificity for focal uptake were 90.6% (95% CI 81.7–99.4%) and 82.8% (95% CI 71.3–94.3%), respectively, for VGS 86.8% (95% CI 59.3–100%) and 69.4% (95% CI 39.9–98.9%), respectively, for SUVmax 92.8% (95% CI 83.2–100%) and 69.7% (95% CI 52.4–86.9%), respectively. A single study employed tissue-to-background ratio (TBR) and found sensitivity and specificity of 71.8% (95% CI 54.6–84.4%) and 70.4% (95% CI 51.5–84.2%), respectively. Conclusions According to this systematic review and meta-analysis, FDG-PET/CT performs well especially when using focal versus diffuse FDG uptake to diagnose VGI.

Sentinel lymph node biopsy in oral–oropharyngeal squamous cell carcinoma: standards, new technical procedures, and clinical advances Abstract Purpose To provide substantial coverage and critical appraisal of standards as well as new technical procedures and clinical advances concerning sentinel lymph node biopsy (SNB) in oral squamous cell carcinoma (OSCC). Methods The MEDLINE database was searched via the PubMed interface up to January 2019 for the following MeSH heading: “sentinel lymph node biopsy” and “squamous cell carcinoma of head and neck”. Results SNB exists as an alternative to elective neck dissection (END) in OSCC. Pre-surgical planar lymphoscintigraphy with intra-operative hand-held gamma probe allows using SNB. Furthermore, the contribution of pre-surgical SPECT/CT improves the sentinel lymph node (SLN) roadmap in sites that are closer to the injection site. Portable gamma camera and freehand SPECT are not yet routine clinical practice, but can further improve intra-operative SLN detection. However, the difficulty in detecting SLNs located closer to the injection site persists. SNB with combined radioactive and near-infrared fluorescence guidance is an attractive option for improving spatial resolution of radio-guided techniques while maintaining depth penetration. Conclusion Numerous studies have demonstrated that SNB can be proposed for accurate histopathological staging of the neck and the guidelines support the introduction of SNB as an alternative to END in T1/T2 N0 OSCC patients. New hybrid imaging techniques, which are offering new possibilities to assist clinicians and surgeons in localizing the site of uptake in sentinel node detection, need to be confirmed in ongoing and future clinical trials. In the future, the integration of new PET tracers could continue along the route mapped out in SNB.

A look ahead: future directions of SSR-directed imaging and therapy in meningioma Abstract Background Meningiomas, which are the most common of CNS tumours in adults, show a high expression of the somatostatin receptor subtype 2 (SSR). Visualization of these receptors with specific PET ligands augments contrast-enhanced MRI and CT of the brain in resolving several clinical issues related to differential diagnosis, evaluation of meningioma extent, and therapy planning or follow-up. Moreover, SSR-directed radioligands labeled with beta-emitters serve for radiopeptide therapy (RPT) in patients with recurrent or refractory meningioma. In the light of recent developments in radiochemistry, neuropathology/molecular genetics, and emerging systemic treatments, we present our perspective on future directions of SSR-directed imaging and therapy in meningioma. Methods We conducted a search in the PubMed literature database until June 2019 using the terms “meningioma”, “PET”, “somatostatin receptor”, “SS(T)R”, “DOTATATE”, “DOTATOC”, “radiopeptide therapy”, “imaging”, “therapy”, “classification” alone and in combination, compiled with relevant literature from the authors’ own files. Results/conclusion Our review identifies important emerging applications of SSR-directed imaging and therapy in patients with meningioma. We summarize the state of development novel SSR-directed radio-ligands, meningioma classifications and systemic treatment options.