Head-to-head comparison between F-18-DOPA PET/CT and Ga-68-DOTA-peptide PET/CT in detecting intestinal neuroendocrine tumours:A systematic review and meta-analysis

Objective: The imaging of intestinal neuroendocrine tumours (NETs) relies on functional PET tracers; these tumours can be studied by means of both Ga-68-DOTA-peptides and F-18-DOPA PET/CT. As yet, it is unclear which of these two modalities offers the better sensitivity. We therefore conducted a meta-analysis to assess the available data. Design: PubMed, CENTRAL, Scopus and Web of Science were searched for studies comparing the sensitivity of Ga-68-DOTA-peptides and F-18-DOPA PET/CT; papers up to February 2021 were considered. Patients and Measurements: In each study, we considered sensitivity in terms of patient-based (PBA), region-based (RBA) and lesion-based analysis (LBA) and pooled the results yielded by each tracer. Multidisciplinary follow-up served as the standard of truth. Results: Of the 636 records identified, 6 articles published between 2008 and 2021 were finally selected, and 112 intestinal NET patients were included. The pooled sensitivity of F-18-DOPA PET/CT was 83%, 89% and 95% on PBA, RBA and LBA, respectively. Ga-68-DOTA peptide PET/CT showed sensitivity of 88%, 92% and 82% on PBA, RBA and LBA, respectively. No significant differences were found between the two tracers on PBA and RBA. By contrast, a clear trend towards significance in favour of F-18-DOPA PET/CT was identified on LBA. The presence of a significant difference in favour of F-18-DOPA PET/CT was confirmed in a subgroup analysis conducted only on the most recent and largest studies. In all three analyses, mild-to-high heterogeneity was found, while no publication bias was observed. Conclusion: Both F-18-DOPA PET/CT and Ga-68-DOTA-peptide PET/CT are reliable diagnostic procedures in patients with intestinal NETs. However, in terms of lesion detection, a non-negligible difference in favour of F-18-DOPA PET/CT was observed. Thus, the use of F-18-DOPA PET/CT could be considered as a first-line molecular procedure in intestinal NETs

Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective

Metachromatic leukodystrophy (MLD) is an autosomal recessively inherited metabolic disease characterized by deficient activity of the lysosomal enzyme arylsulfatase A. Its deficiency results in accumulation of sulfatides in neural and visceral tissues, and causes demyelination of the central and peripheral nervous system. This leads to a broad range of neurological symptoms and eventually premature death. In asymptomatic patients with juvenile and adult MLD, treatment with allogeneic hematopoietic stem cell transplantation (HCT) provides a symptomatic and survival benefit. However, this treatment mainly impacts brain white matter, whereas the peripheral neuropathy shows no or only limited response. Data about the impact of peripheral neuropathy in MLD patients are currently lacking, although in our experience peripheral neuropathy causes significant morbidity due to neuropathic pain, foot deformities and neurogenic bladder disturbances. Besides, the reasons for residual and often progressive peripheral neuropathy after HCT are not fully understood. Preliminary studies suggest that peripheral neuropathy might respond better to gene therapy due to higher enzyme levels achieved than with HCT. However, histopathological and clinical findings also suggest a role of neuroinflammation in the pathology of peripheral neuropathy in MLD. In this literature review, we discuss clinical aspects, pathological findings, distribution of mutations, and treatment approaches in MLD with particular emphasis on peripheral neuropathy. We believe that future therapies need more emphasis on the management of peripheral neuropathy, and additional research is needed to optimize care strategies