Hypoxia plays a critical role in tumor development and aggressiveness and is an important prognostic factor for resistance to antineoplastic treatments; therefore, it is required to measure the hypoxic level of tumor for a favorable outcome. The pretherapy information on the oxygenation status of a tumor microenvironment should also have implications for treatment selection. A diffuse distribution of hypoxia in a tumor might suggest a benefit from a systemic approach, such as a hypoxic cell cytotoxin, tirapazamine, or antigrowth factor drugs to combat the limitations of hypoxia. Alternatively, a more focal hypoxia might benefit from a local/regional approach, such as intensity-modulated radiation therapy-based radiation dose escalation to the hypoxic subvolume. This review anticipates that (18)F-FMISO ((18)F-fluoromisonodazole) and (64)Cu-ATSM-positron emission tomography (PET) will prove useful for selecting individual patients for the most appropriate treatment. The advent of new radiotracers has allowed noninvasive assessment of hypoxia, with the most extensively investigated and validated PET radiotracer for hypoxia to date being (18)F-FMISO. This article discusses the relevance and biology of hypoxia in cells and organ systems and reviews the laboratory and clinical applications of (18)F-FMISO and other agents in oncology.

Nature Communications

Dynamic PET reveals compartmentalized brain and lung tissue antibiotic exposures of tuberculosis drugs

Article

Author: Jeon, Byeonghoon ; Carroll, Laurence S ; Singh, Medha ; Chen, Xueyi ; Ivaturi, Vijay D ; Shah, Maunank ; Peloquin, Charles A ; Nino-Meza, Oscar J ; Arun, Bhavatharini ; Sarhan, Mona O ; Mane, Kishor ; Freundlich, Joel S ; Jain, Sanjay K ; Tucker, Elizabeth W

Tuberculosis (TB) remains a leading cause of death, but antibiotic treatments for tuberculous meningitis, the deadliest form of TB, are based on those developed for pulmonary TB and not optimized for brain penetration. Here, we perform first-in-human dynamic ¹⁸F-pretomanid positron emission tomography (PET) in eight human subjects to visualize ¹⁸F-pretomanid biodistribution as concentration-time exposures in multiple compartments (NCT05609552), demonstrating preferential brain versus lung tissue partitioning. Preferential, antibiotic-specific partitioning into brain or lung tissues of several antibiotics, active against multidrug resistant (MDR) Mycobacterium tuberculosis strains, are confirmed in experimentally-infected mice and rabbits, using dynamic PET with chemically identical antibiotic radioanalogs, and postmortem mass spectrometry measurements. PET-facilitated pharmacokinetic modeling predicts human dosing necessary to attain therapeutic brain exposures. These data are used to design optimized, pretomanid-based regimens which are evaluated at human equipotent dosing in a mouse model of TB meningitis, demonstrating excellent bactericidal activity without an increase in intracerebral inflammation or brain injury. Importantly, several antibiotic regimens demonstrate discordant activities in brain and lung tissues in the same animal, correlating with tissue antibiotic exposures. These data provide a mechanistic basis for the compartmentalized activities of antibiotic regimens, with important implications for developing treatments for meningitis and other infections in compartments with unique antibiotic penetration.

Hellenic journal of nuclear medicine

Analysis of the diagnostic effect of ¹⁸F-FDG PET/CT in IIM patients and its relationship with disease severity.

Article

Author: Liu, Lu ; Wang, Na ; Wang, Binbin ; Sun, Yanpeng ; Chen, Yuqian

OBJECTIVETo analyze the diagnostic effect of fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) in patients with idiopathic inflammatory myopathies (IIM) and its relationship with disease severity.SUBJECTS AND METHODSA retrospective analysis was conducted on the clinical and imaging data of 31 IIM patients treated in our hospital from April 2020 to April 2024, who were included in the lesion group. Additionally, 30 patients without muscle disease during the same period were selected as the control group. The maximum standardized uptake value (SUVmax) of the proximal limb girdle muscles was measured in both groups and compared. A receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic value of SUVmax for IIM using ¹⁸F-FDG PET/CT. Spearman rank correlation was used to analyze the relationship between muscle SUVmax in IIM patients and relevant laboratory indicators, including creatine kinase (CK), creatine kinase-MB (CK-MB), C-reactive protein (CRP), serum ferritin (SF), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT).RESULTSThe SUVmax level of the lesion group (2.94±0.58) was significantly higher than that of the control group (1.17±0.23) (t=15.568, P<0.05). A receiver operating characteristic curve analysis indicated that the optimal cut-off value of SUVmax for distinguishing the lesion group from the control group was 2.16g/mL, with a diagnostic sensitivity of 100%, specificity of 91.8%, and an area under the curve (AUC) of 0.952. Correlation analysis showed a positive correlation between SUVmax and CK (r=0.659), CK-MB (r=0.523), AST (r=0.458), and LDH (r=0.437) (P<0.05), but no significant correlation with CRP (r=0.219), SF (r=0.348), or ALT (r=0.237).CONCLUSIONFluorine-18-FDG PET/CT demonstrates an ideal diagnostic effect for IIM patients, and its semi-quantitative parameter, SUVmax, holds good auxiliary diagnostic value for IIM. It can reflect the activity and severity of the disease to a certain extent.

100 Deals associated with F-18 quinoline

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Preclinical	US	The University of Texas at Dallas	01 Jul 2013

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