[18F]NOS PET/CT Scan for Neuroinflammation
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Pennsylvania
Must be taking: ART, OUD treatment
Disqualifiers: Pregnancy, Epilepsy, Schizophrenia, Claustrophobia, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this research is to measure the extent of inflammation in the brain between different groups of participants using a radioactive tracer called \[18F\]NOS. A radioactive tracer is a type of imaging drug that is labeled with a radioactive tag and injected into the body. This study will see how the tracer is taken up in the brain using an imaging scan called Positron Emission Tomography / Computed Tomography (PET/CT).
Participants will undergo approximately 60 minutes of dynamic scanning of the brain starting at approximately the time of injection of \[18F\]NOS.
Participants are required to have a brain MRI performed within 1 year prior to study enrollment, or if the subject has not had a brain MRI that is deemed acceptable for use for this study they will be asked to undergo a research brain MRI after they have consented for this study.
Will I have to stop taking my current medications?
The trial requires participants with HIV to stay on a stable ART regimen (HIV treatment) and those with OUD to be on a stable dosage of OUD treatment for at least four weeks before the screening. The protocol does not specify other medication restrictions.
How does the [18F]NOS PET/CT scan differ from other treatments for neuroinflammation?
The [18F]NOS PET/CT scan is unique because it uses a radiolabeled tracer to specifically target and visualize inducible nitric oxide synthase (iNOS), a key enzyme involved in neuroinflammation, allowing for non-invasive imaging of inflammation in the brain. This approach is different from traditional treatments as it focuses on detecting and measuring inflammation rather than directly treating it.
12345Eligibility Criteria
This trial is for adults aged 18-65 with or without HIV and opioid use disorder (OUD). Participants must have stable health conditions, including a controlled viral load if HIV positive, and be on consistent OUD treatment if applicable. Pregnant or breastfeeding women, individuals over 350 lb, those with claustrophobia affecting scans, MRI contraindications like incompatible metal in the body, significant organ dysfunction, epilepsy/seizure disorders, severe head trauma history, certain psychiatric disorders including schizophrenia or active major depression with suicidal ideation are excluded.Inclusion Criteria
I am 18-65, HIV negative, have never had opioid use disorder, and haven't used opioids in the last 30 days.
I am 18-65, have HIV and opioid use disorder, on stable treatments for both, and my viral load and CD4+ count are within required ranges.
I am 18-65, HIV positive, not using opioids, with controlled HIV on stable treatment.
+1 more
Exclusion Criteria
Claustrophobia that may interfere with MRI acquisition or PET scan
Current psychiatric disorder
History of head trauma
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Imaging
Participants undergo PET/CT imaging to measure neuroinflammation using [18F]NOS tracer
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after imaging
4 weeks
Participant Groups
The study tests how a radioactive tracer called [18F]NOS behaves in the brain to measure inflammation levels using PET/CT imaging. It involves an injection of [18F]NOS followed by about an hour-long dynamic brain scan. The research includes people both with and without HIV/OUD to compare results across different health statuses.
4Treatment groups
Experimental Treatment
Group I: Healthy volunteerExperimental Treatment1 Intervention
HIV-, OUD- healthy controls who have been opioid-exposed but do not have current or past OUD
Group II: HIV positive (HIV+) subjects with Opioid Use Disorder (OUD)Experimental Treatment1 Intervention
HIV positive (HIV+) subjects with Opioid Use Disorder (OUD): HIV+/OUD+
Group III: HIV negative (HIV-) subjects with OUDExperimental Treatment1 Intervention
HIV negative (HIV-) subjects with OUD: HIV-/OUD+
Group IV: HIV Positive (HIV+) subjects with OUD negativeExperimental Treatment1 Intervention
HIV+ subjects who may have been opioid-exposed but do not have current or past OUD
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of PennsylvaniaPhiladelphia, PA
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Who Is Running the Clinical Trial?
University of PennsylvaniaLead Sponsor
References
Automated Synthesis and Initial Evaluation of (4'-Amino-5',8'-difluoro-1'H-spiro[piperidine-4,2'-quinazolin]-1-yl)(4-[18F]fluorophenyl)methanone for PET/MR Imaging of Inducible Nitric Oxide Synthase. [2021]Label="Background">Inducible nitric oxide synthase (iNOS) plays a crucial role in neuroinflammation, especially microglial activity, and may potentially represent a useful biomarker of neuroinflammation. In this study, we carefully defined a strategic plan to develop iNOS-targeted molecular PET imaging using (4'-amino-5',8'-difluoro-1'H-spiro[piperidine-4,2'-quinazolin]-1-yl)(4-fluorophenyl)methanone ([18F]FBAT) as a tracer in a mouse model of lipopolysaccharide- (LPS-) induced brain inflammation.
Design and synthesis of 2-amino-4-methylpyridine analogues as inhibitors for inducible nitric oxide synthase and in vivo evaluation of [18F]6-(2-fluoropropyl)-4-methyl-pyridin-2-amine as a potential PET tracer for inducible nitric oxide synthase. [2021]A series of position-6 substituted 2-amino-4-methylpyridine analogues was synthesized and compounds 9, 18, and 20 were identified as the inhibitors with the greatest potential to serve as PET tracers for imaging inducible nitric oxide synthase (iNOS). [(18)F]9 was synthesized and evaluated in a mouse model of lipopolysaccharide (LPS)-induced iNOS activation. In vivo biodistribution studies of [(18)F]9 indicate higher tracer uptake in the lungs of the LPS-treated mice when compared to control mice. Tracer uptake at 60 min postinjection was reduced in a blocking study using a known inhibitor of iNOS. The expression of iNOS was confirmed by Western blot analysis of lung samples from the LPS-treated mice. MicroPET studies also demonstrated accumulation of radiotracer in the lungs of the LPS-treated mice. Taken collectively, these data suggest that [(18)F]9 shows favorable properties as a PET tracer to image iNOS activation with PET.
Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added (18)F-Labelling Methods. [2020]Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and (18)F-labelled analogues would allow investigating the NOS-function by molecular imaging with positron emission tomography. Especially, the highly selective nNOS inhibitor 6-((3-((3-fluorophenethylamino)methyl)phenoxy)methyl)-4-methylpyridin-2-amine (10) lends itself as suitable compound to be (18)F-labelled in no-carrier-added (n.c.a.) form. For preparation of the (18)F-labelled nNOS-Inhibitor [(18)F]10 a "build-up" radiosynthesis was developed based on a corresponding iodonium ylide as labelling precursor. The such activated phenethyl group of the compound was efficiently and regioselectively labelled with n.c.a. [(18)F]fluoride in 79% radiochemical yield (RCY). After conversion by reductive amination and microwave assisted displacement of the protecting groups, the desired nNOS-inhibitor was obtained in about 15% total RCY. Alternatively, for a simplified "late-stage" (18)F-labelling procedure a corresponding boronic ester precursor was synthesized and successfully used in a newer, copper(II) mediated n.c.a. (18)F-fluoro-deboroniation reaction, achieving the same total RCY. Thus, both methods proved comparatively suited to provide the highly selective NOS-inhibitor [(18)F]10 as probe for preclinical in vivo studies.
Feasibility and dosimetry studies for 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans. [2021]Nitric oxide (NO), the end product of the inducible form of NO synthase (iNOS), is an important mediator of a variety of inflammatory diseases. Therefore, a radiolabeled iNOS radiopharmaceutical for assessing iNOS protein concentration as a marker for its activity would be of value to the study and treatment of NO-related diseases. We recently synthesized an (18)F-radiolabeled analog of the reversible NOS inhibitor, 2-amino-4-methylpyridine ((18)F-NOS), and confirmed its utility in a murine model of lung inflammation. To determine its potential for use in humans, we measured (18)F-NOS myocardial activity in patients after orthotopic heart transplantation (OHT) and correlated it with pathologic allograft rejection, tissue iNOS levels, and calculated human radiation dosimetry.
[18F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson's Disease. [2023]Neuroinflammation is implicated as a key pathologic mechanism in many neurodegenerative diseases and is thought to be mediated in large part by microglia, native phagocytic immune cells of the CNS. Abnormal aggregation of the protein α-synuclein after phagocytosis by microglia is one possible neuropathophysiological mechanism driving Parkinson's disease (PD). We conducted a human pilot study to evaluate the feasibility of targeting the inducible isoform of nitric oxide synthase using the [18F]NOS radiotracer to measure neuroinflammation in idiopathic PD. Ten adults consisting of 6 PD patients and 4 healthy controls (HC) underwent one hour of dynamic [18F]NOS positron emission tomography (PET) brain imaging with arterial blood sampling. We observed increased [18F]NOS whole brain distribution volume (VT) in PD patients compared to age-matched healthy controls (p < 0.008) via a 1-tissue compartment (TC) model. The rate constant K1 for transport from blood into tissue did not differ between groups (p = 0.72). These findings suggest elevated oxidative stress, a surrogate marker of inflammation, is present in early-stage idiopathic PD and indicate that [18F]NOS PET imaging is a promising, non-invasive method to measure neuroinflammation.