The absence of a gold standard to determine when antibiotics induce a sterilizing cure has confounded the development of new approaches to treat pulmonary tuberculosis (PTB). We detected positron emission tomography and computerized tomography (PET-CT) imaging response patterns consistent with active disease, along with the presence of Mycobacterium tuberculosis (MTB) mRNA in sputum and bronchoalveolar lavage samples, in a substantial proportion of adult, HIV-negative patients with PTB after a standard 6-month treatment plus 1 year follow-up, including patients with a durable cure and others who later developed recurrent disease. The presence of MTB mRNA in the context of nonresolving and intensifying lesions on PET-CT images might indicate ongoing transcription, suggesting that even apparently curative treatment for PTB may not eradicate all of the MTB bacteria in most patients. This suggests an important complementary role for the immune response in maintaining a disease-free state. Sterilizing drugs or host-directed therapies, and better treatment response markers, are probably needed for the successful development of improved and shortened PTB-treatment strategies.
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http://dx.doi.org/10.1038/nm.4177 | DOI Listing |
EJNMMI Radiopharm Chem
December 2024
Department of Experimental Neurooncological Radiopharmacy, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig, Permoserstrasse 15, 04318, Leipzig, Germany.
Background: The cannabinoid type 2 receptors (CB2R) represent a target of increasing importance in neuroimaging due to its upregulation under various neuropathological conditions. Previous evaluation of [F]JHU94620 for the non-invasive assessment of the CB2R availability by positron emission tomography (PET) revealed favourable binding properties and brain uptake, however rapid metabolism, and generation of brain-penetrating radiometabolites have been its main limitations. To reduce the bias of CB2R quantification by blood-brain barrier (BBB)-penetrating radiometabolites, we aimed to improve the metabolic stability by developing -d and -d deuterated isotopologues of [F]JHU94620.
View Article and Find Full Text PDFJ ECT
December 2024
Department of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium.
Electroconvulsive therapy (ECT) effectively treats severe psychiatric disorders such as depression, mania, catatonia, and schizophrenia. Although its exact mechanism remains unclear, ECT is thought to induce neurochemical and neuroendocrine changes. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) have provided vital insights into ECT's neurobiological effects.
View Article and Find Full Text PDFRheumatology (Oxford)
December 2024
Department of Radiology, University of California Davis, Sacramento, CA, USA.
Objectives: To test the hypothesis that recently-developed total body-positron emission tomography (TB-PET) imaging with integrated computed tomography (CT) will enable low-dose, quantitative, domain-specific evaluation of the total inflammatory burden of psoriatic arthritis (PsA), and associate with established outcome measures of the clinical domains of PsA.
Methods: Seventy-one adult participants (40 with PsA, 16 with rheumatoid arthritis (RA), and 15 with osteoarthritis (OA)) underwent 20-min TB-PET/CT scans using [18F]FDG, a glucose analogue radiotracer. [18F]FDG uptake was assessed qualitatively and quantitatively.
Ann Neurol
December 2024
Department of Neurology, Washington University School of Medicine, St. Louis, MO.
Objective: Despite treatments which reduce relapses in multiple sclerosis (MS), many patients continue to experience progressive disability accumulation. MS is associated with metabolic disruptions and cerebral metabolic stress predisposes to tissue injury and possibly impaired remyelination. Additionally, myelin homeostasis is metabolically expensive and reliant on glycolysis.
View Article and Find Full Text PDFACS Nano
December 2024
Zhejiang Cancer Hospital, The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
Nanobodies are promising for immunoPET imaging due to their excellent antigen recognition and tumor targeting, yet rapid clearance limits their tumor accumulation. Although multimerization and albumin binding can extend their circulation time and improve tumor targeting, a simple and universal method for creating protein multimers is still needed. Here, we leveraged the facile synthesis, controllable size, and precise assembly of DNA nanotechnology to construct CD47-targeted framework nucleic acid-nanobody fusion probes with multiple valences and sizes.
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