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[18F]ZDG2 First-in-Human PET Imaging in PAH

11. listopadu 2026 aktualizováno: The Methodist Hospital Research Institute

First-in-Human PET Imaging of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension Using [18F]ZDG2: Safety, Biodistribution, Dosimetry and Pharmacokinetics

The goal of this study is to find out whether [18F]ZDG2 can detect early blood vessel changes in people with pulmonary arterial hypertension (PAH). The study will help answer this question:

Can a positron emission tomography (PET) scan using [18F]ZDG2 help identify PAH?

Participants will:

  • Receive one or two doses of the study tracer [18F]ZDG2 and have a PET/CT scan after each dose
  • Provide blood and urine samples
  • Tell the study team about any side effects or symptoms you experience

Přehled studie

Postavení

Zatím nenabíráme

Podmínky

Intervence / Léčba

Detailní popis

Pulmonary arterial hypertension (PAH) affects approximately 220,000 people in the United States and more than 2 million people worldwide. There is currently no cure, and despite available treatments, the five-year mortality rate remains approximately 50%. Diagnosis is often delayed by more than two years because commonly used screening tests lack accuracy, while the gold-standard diagnostic test requires invasive right heart catheterization. By the time PAH is diagnosed, patients may have already lost up to 70% of their pulmonary vascular reserve, resulting in irreversible disease progression.

Current diagnosis is based on elevated pulmonary artery pressure, a relatively late manifestation of the disease, rather than the underlying biological changes that occur during its early stages. One of these early changes is pulmonary vascular remodeling, which leads to loss of pulmonary vascular reserve and is driven in part by vascular endothelial growth factor (VEGF) signaling.

To address this unmet need, we have developed an imaging tracer designed to detect these early molecular changes by targeting dysregulation of vascular endothelial growth factor receptor 2 (VEGFR2). Houston Methodist Research Institute has developed [18F]ZDG2, a novel PET imaging tracer that selectively binds to VEGFR2 and can be visualized using positron emission tomography. This approach may enable noninvasive measurement of VEGFR2 expression and provide a means to detect PAH at earlier stages of disease, before significant and irreversible vascular damage has occurred.

Typ studie

Intervenční

Zápis (Odhadovaný)

20

Fáze

  • Raná fáze 1

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

21 let až 75 let (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ano

Pohlaví způsobilá ke studiu

Všechno

Popis

Healthy Volunteer Criteria

Inclusion Criteria- Healthy Volunteers

  1. Age 21-75 years (inclusive) at time of consent

  2. Body Mass Index 18.5-35 kg/m²

  3. Willing and able to provide written informed consent

  4. Willing and able to comply with all study procedures

  5. Able to lie flat in supine position for 60 minutes without significant discomfort

  6. No history of cardiovascular disease including:

    • Symptomatic Coronary artery disease
    • Significant Valvular heart disease (stenotic or regurgative disease of moderate or grater severity)
    • Congenital heart disease
    • Symptomatic Arrhythmias
    • Pulmonary hypertension
    • Thromboembolic disease (history of recurrent pulmonary embolisms)

  7. Normal baseline electrocardiogram within 28 days

  8. Normal baseline echocardiogram within 6 months demonstrating:

    • Normal RV size and systolic function (Tricuspid Annular Plane Systolic Excursion>17 mm)
    • No tricuspid regurgitation jet or estimated Right Ventricular Systolic Pressure <35 mmHg
    • Normal Left Ventricle size and systolic function (Left Ventricular Ejection Fraction ≥50%)
    • No significant valvular disease

  9. Baseline NT-proBNP <125 pg/mL (or BNP <50 pg/mL)

  10. Non-smoker OR former smoker with quit date ≥1 year ago and <10 pack-year history

  11. For women of childbearing potential:

    -Agrees to use highly effective contraception from screening through 30 days after imaging

  12. For men with Women of Childbearing Potential partners:

    • Agrees to use barrier contraception from screening through 30 days after imaging

Exclusion Criteria- Healthy Volunteers

  1. Active cancer (except non-melanoma skin cancer >2 years disease-free), metabolic encephalopathy, infection, or cardiovascular disease.

  2. Active hematological, renal, pulmonary, endocrine, or hepatic disorders, except for treated thyroid disease.

  3. History of pulmonary disease including:

    • Asthma
    • Chronic Obstructive Pulmonary Disease
    • Interstitial lung disease
    • Prior pneumonia with residual changes
    • Sleep apnea

  4. Participation in any investigational diagnostic or therapeutic radiopharmaceutical studies in the last year.

  5. Coronary revascularization (Percutaneous Coronary Intervention or Coronary Artery Bypass Graft) within 6 months

  6. Stroke or Transient Ischemic Attack within 6 months

  7. Uncontrolled systemic hypertension (Systolic Blood Pressure(SBP)>160 or Diastolic Blood Pressure(DBP)>100 mmHg)

  8. Resting systolic blood pressure <90 mmHg

  9. Clinically significant arrhythmia requiring treatment

  10. Use of any prescription medication

  11. Significant alcohol use (>14 drinks/week for men, >7 drinks/week for women)

  12. Illicit drug use within 2 years (including, use of stimulants such as methamphetamine)

  13. Use of amphetamine weight loss drugs

  14. Portal hypertension

  15. Radiation exposure >50 mSv in the past 12 months

  16. Occupational radiation exposure

  17. Known genetic risk factors for PAH (ex: Bone Morphogenetic Protein Receptor Type 2 mutations)

  18. History of scleroderma

  19. History of pre-term birth

  20. History of Human Immunodeficiency Virus

  21. Known allergy or hypersensitivity to any component of the investigational product

  22. Contraindication to Positron Emission Tomography / Computed Tomography imaging

  23. Weight >227 kg (500 lbs. - scanner table limit)

  24. Any condition that, in the opinion of the investigator, would compromise subject safety or study data quality

  25. Incarceration

PAH Patients Criteria

Inclusion Criteria- PAH Patients

  1. Age 21-75 years (inclusive) at time of consent

  2. Body Mass Index 18.5-40 kg/m²

  3. Willing and able to provide written informed consent

  4. Willing and able to comply with all study procedures

  5. Able to lie flat (or semi-recumbent with 15-30° elevation) for 60 minutes

  6. Confirmed diagnosis of pulmonary arterial hypertension (World Health Organization (WHO) Group 1) by right heart catheterization meeting ALL of the following hemodynamic criteria within the last 3 months:

    • Mean pulmonary artery pressure ≥20 mmHg
    • Pulmonary artery wedge pressure ≤15 mmHg
    • Pulmonary vascular resistance ≥3 Wood Units

  7. PAH etiology limited to WHO Group 1 subtypes:

    • Idiopathic PAH

    • Heritable PAH

    • Drug or toxin-induced PAH

    • Associated PAH including:

      • Connective tissue disease: scleroderma, lupus, Mixed Connective Tissue Disease, etc.
      • Congenital heart disease: repaired shunts only
      • Portal hypertension
      • HIV infection

  8. WHO Functional Class I, II or III:

    • Class I: No limitation of physical activity
    • Class II: Slight limitation of physical activity; ordinary activity causes symptoms
    • Class III: Marked limitation of physical activity; less than ordinary activity causes symptoms

  9. 6-minute walk distance: 150-450 meters (performed with 8 weeks of screening)

    -≥150 meters: Ensures patient can complete study procedures

    -≤450 meters: Ensures meaningful disease severity for signal detection

  10. Adequate organ function:

    • Serum creatinine ≤2.0 mg/dL OR estimated Creatinine Clearance ≥30 mL/min
    • AST/ALT ≤2.5× ULN
    • Total bilirubin ≤1.5× ULN

  11. Clinically stable for ≥8 weeks prior to enrollment:

    • No hospitalization for PAH or heart failure
    • No PAH exacerbation or clinical worsening
    • No syncope or presyncope
    • No escalation of diuretic dose for >2 weeks

  12. Stable PAH-specific medication regimen for ≥8 weeks:

    • No addition, discontinuation, or dose change of:
    • Endothelin receptor antagonists
    • Phosphodiesterase-5 inhibitors
    • Soluble guanylate cyclase stimulators
    • Prostacyclin pathway agents
    • Activin Receptor Antagonist (Sotatercept)

  13. Comprehensive echocardiogram within 8 weeks demonstrating:

    • RV size and function quantified (TAPSE, RV S')
    • Estimated RVSP documented, if adequate tricuspid regurgitation jet available
    • No severe LV dysfunction (LVEF ≥40%)
    • No more than moderate valvular disease

  14. Pulmonary function tests (as measured per standard of care) within 12 months demonstrating:

    • Forced Expiratory Volume(FEV)1/Forced Vital Capacity (FVC) >0.70 OR if <0.70, FEV1 >60% predicted
    • DLCO >30% predicted

  15. High-resolution chest CT (as measured per standard of care) within 12 months demonstrating:

    • No significant parenchymal lung disease (emphysema, fibrosis)
    • Enlarged main pulmonary artery typical of PH (PA diameter >29 mm)
    • No evidence of chronic thromboembolic disease

  16. Ventilation-perfusion scan (as measured per standard of care) within 12 months demonstrating:

    • Low probability OR normal study
    • No mismatched perfusion defects (excludes Chronic Thromboembolic Pulmonary Hypertension)

  17. For Women Of Childbearing Potential:

    -Agrees to use highly effective contraception through 30 days after imaging

  18. For men with Women Of Childbearing Potential partners:

    -Agrees to use barrier contraception through 30 days after imaging

  19. Life expectancy ≥6 months in the judgment of the investigator

Exclusion Criteria- PAH Patients

  1. Acute coronary syndrome within 6 months

  2. Coronary revascularization (PCI or CABG) within 6 months

  3. Stroke or TIA within 6 months

  4. Uncontrolled systemic hypertension (SBP >160 or DBP >100 mmHg)

  5. Resting systolic blood pressure <90 mmHg

  6. Clinically significant arrhythmia requiring treatment (except stable atrial fibrillation)

  7. Active pulmonary infection or pneumonia within 3 months

  8. Pulmonary embolism (acute) within 6 months

  9. Classification of other PH groups confirmed by:

    • Group 2 (LHD): PAWP ≤15 mmHg, no significant LV disease on echo
    • Group 3 (lung disease): FEV1/FVC >0.70 OR FEV1 >60% if obstructive; DLCO >40% predicted; no significant interstitial lung disease on CT in the past 12 months (If no PFT available for the past 12 months patient will need one at the time of screening)
    • Group 4 (CTEPH): Ventilation-perfusion scan any time since diagnosis showing low probability or normal (no mismatched defects)
    • Group 5: No evidence of multifactorial/unclear PH mechanisms
    • For PAH: Significant Group 2, 3, 4, or 5 PH contribution

  10. WHO Functional Class IV (symptoms at rest - too sick for study)

  11. Radiation exposure >50 mSv in the past 12 months

  12. Occupational radiation exposure

  13. Cirrhosis with portal hypertension

  14. Known allergy or hypersensitivity to any component of the investigational product

  15. Contraindication to PET/CT imaging

  16. Weight >227 kg (500 lbs. - scanner table limit)

  17. Active malignancy (except non-melanoma skin cancer >2 years disease-free)

  18. Participation in any investigational diagnostic or therapeutic radiopharmaceutical studies in the last year.

  19. Any condition that, in the opinion of the investigator, would compromise subject safety or study data quality

  20. Incarceration

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Diagnostický
  • Přidělení: N/A
  • Intervenční model: Přiřazení jedné skupiny
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: PAH Patients

Patients diagnosed with PAH will receive the tracer. A subset (10/12) will participate in reproducibility testing.
Lék: [18F]ZDG2- Single Dose

[18F]ZDG2 will be administered as an intravenous injection on the day of imaging. Participants in the reproducibility cohort will receive an additional dose and imaging session one to weeks after the first.

Heathy volunteers and PAH patients not in the reproducibility cohort will receive only one dose and imaging session.
Experimentální: Healthy Volunteers

Healthy volunteers will receive the tracer.
Lék: [18F]ZDG2- Single Dose

[18F]ZDG2 will be administered as an intravenous injection on the day of imaging. Participants in the reproducibility cohort will receive an additional dose and imaging session one to weeks after the first.

Heathy volunteers and PAH patients not in the reproducibility cohort will receive only one dose and imaging session.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Incidence and severity of adverse events
Časové okno: From enrolment to the final follow up visit, 3-7 days after the last dose.

Incidence recorded and severity graded per CTCAE v6.0
From enrolment to the final follow up visit, 3-7 days after the last dose.
Changes in blood pressure from baseline
Časové okno: From enrolment to the final follow up visit, 3-7 days after the last dose.

Systolic and diastolic (mmHg)
From enrolment to the final follow up visit, 3-7 days after the last dose.
Changes in heart rate from baseline
Časové okno: From enrolment to the final follow up visit, 3-7 days after the last dose.

(bpm)
From enrolment to the final follow up visit, 3-7 days after the last dose.
Changes in oxygen saturation from baseline
Časové okno: From enrolment to the final follow up visit, 3-7 days after the last dose.

As measured via pulse oximetry (%)
From enrolment to the final follow up visit, 3-7 days after the last dose.
Changes in temperature from baseline
Časové okno: From enrolment to the final follow up visit, 3-7 days after the last dose.

(°C or °F)
From enrolment to the final follow up visit, 3-7 days after the last dose.
Standardized uptake values in major organs
Časové okno: From tracer administration to the final scan at 180 minutes post administration

(SUVmax, SUVmean)
From tracer administration to the final scan at 180 minutes post administration
Number of participants with abnormal results in hematology assessments
Časové okno: From enrolment to the final follow up visit, 3-7 days after the last dose.

The following will be assessed as part of the hematology panel:

WBC, Platelet count, RBC, Neutrophils, HGB, Lymphocytes, HCT, Monocytes, MCV, Eosinophils, MCH, Basophils, MCHC Changes from baseline and results outside of the normal range will be evaluated by the PI and safety committee for clinical significance.
From enrolment to the final follow up visit, 3-7 days after the last dose.
Number of participants with abnormal results in chemistry laboratory assessments
Časové okno: From enrolment to the final follow up visit, 3-7 days after the last dose.

The following will be assessed as part of the chemistry panel:

Sodium, Calcium, Potassium, Protein, Chloride, Albumin, CO2, Alkaline phosphatase, BUN, AST, Creatinine, ALT, Glucose, Total bilirubin, eGFR Changes from baseline and results outside of the normal range will be evaluated by the PI and safety committee for clinical significance.
From enrolment to the final follow up visit, 3-7 days after the last dose.
Number of participants with abnormal results in coagulation laboratory assessments
Časové okno: From enrolment to the final follow up visit, 3-7 days after the last dose.

The following will be assessed as part of the coagulation panel:

INR, Prothrombin time (PT) Changes from baseline and results outside of the normal range will be evaluated by the PI and safety committee for clinical significance.
From enrolment to the final follow up visit, 3-7 days after the last dose.
Number of participants with abnormal results in urinalysis laboratory assessments
Časové okno: From enrolment to the final follow up visit, 3-7 days after the last dose.

The following will be assessed as part of the urinalysis panel:

Color, Bilirubin, Appearance, Blood, Specific gravity, Nitrite, pH, Urobilinogen, Protein, WBC, Glucose, RBC, Ketones Changes from baseline and results outside of the normal range will be evaluated by the PI and safety committee for clinical significance.
From enrolment to the final follow up visit, 3-7 days after the last dose.
Number of participants with abnormal results in NTproBNP laboratory assessments
Časové okno: From enrolment to the final follow up visit, 3-7 days after the last dose.

Changes from baseline and results outside of the normal range will be evaluated by the PI and safety committee for clinical significance.

(pg/mL)
From enrolment to the final follow up visit, 3-7 days after the last dose.
Number of participants with abnormal results in HgbA1c laboratory assessments
Časové okno: From enrolment to the final follow up visit, 3-7 days after the last dose.

Changes from baseline and results outside of the normal range will be evaluated by the PI and safety committee for clinical significance.

(%)
From enrolment to the final follow up visit, 3-7 days after the last dose.
Time-activity curves for major organs including lungs and heart
Časové okno: From tracer administration to the final scan at 180 minutes post administration

Organ radioactivity concentration measured over time following tracer administration.
From tracer administration to the final scan at 180 minutes post administration
Identification of excretory pathways
Časové okno: From tracer administration to the final scan at 180 minutes post administration

Determined from serial PET imaging and biologic sample analysis following tracer administration.
From tracer administration to the final scan at 180 minutes post administration
Radiation Dosimetry
Časové okno: From tracer administration to the final scan at 180 minutes post administration.

We will calculate organ-specific absorbed radiation doses and the total effective dose.
From tracer administration to the final scan at 180 minutes post administration.
Plasma concentration-time profile
Časové okno: From tracer administration to the final scan at 180 minutes post administration

Plasma tracer concentration measured at multiple timepoints following administration.
From tracer administration to the final scan at 180 minutes post administration
Parent fraction analysis
Časové okno: From tracer administration to the final scan at 180 minutes post administration

metabolite profiling
From tracer administration to the final scan at 180 minutes post administration
Plasma free fraction determination
Časové okno: From tracer administration to the final scan at 180 minutes post administration

Fraction of tracer unbound to plasma proteins, reported as a percentage.
From tracer administration to the final scan at 180 minutes post administration

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
VEGFR Quantification
Časové okno: From 90 minutes post tracer administration to 180 minutes post administration.

We will quantify pulmonary artery and right ventricular VEGFR expression in PAH patients compared to healthy volunteers.
From 90 minutes post tracer administration to 180 minutes post administration.
Mean pulmonary artery pressure
Časové okno: From tracer administration to the final scan at 180 minutes post administration

As measured via standard of care heart catheterization
From tracer administration to the final scan at 180 minutes post administration
Pulmonary vascular resistance
Časové okno: From tracer administration to the final scan at 180 minutes post administration

As measured via standard of care heart catheterization
From tracer administration to the final scan at 180 minutes post administration
Cardiac output
Časové okno: From tracer administration to the final scan at 180 minutes post administration

As measured via standard of care heart catheterization
From tracer administration to the final scan at 180 minutes post administration
Cardiac index
Časové okno: From tracer administration to the final scan at 180 minutes post administration

As measured via standard of care heart catheterization
From tracer administration to the final scan at 180 minutes post administration
WHO functional class
Časové okno: From enrolment to the final follow up visit, 3-7 days after the last dose.

WHO functional class assessed at baseline per standard of care and reported as Class I, II, III, or IV.
From enrolment to the final follow up visit, 3-7 days after the last dose.
Highest pulmonary artery-to-background ratio
Časové okno: From tracer administration to the final scan at 180 minutes post administration.

As assessed via PET imaging
From tracer administration to the final scan at 180 minutes post administration.

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

The Methodist Hospital Research Institute

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Odhadovaný)

14. listopadu 2026

Primární dokončení (Odhadovaný)

30. dubna 2028

Dokončení studie (Odhadovaný)

31. října 2028

Termíny zápisu do studia

První předloženo

29. září 2026

První předloženo, které splnilo kritéria kontroly kvality

11. listopadu 2026

První zveřejněno (Aktuální)

12. listopadu 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

12. listopadu 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

11. listopadu 2026

Naposledy ověřeno

1. listopadu 2026

Více informací

Termíny související s touto studií

Další relevantní podmínky MeSH

Další identifikační čísla studie

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Plánujete sdílet data jednotlivých účastníků (IPD)?

NE

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Studuje lékový produkt regulovaný americkým FDA

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Studuje produkt zařízení regulovaný americkým úřadem FDA

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