^68Ga-grazytracer PET for In Vivo Visualization of Immune Cell Effector Functions
In Vivo Visualization of Immune Cell Effector Functions Using ^68Ga-grazytracer PET: An Exploratory Study of Cancer and Autoimmune Diseases
This is a prospective, single-center, exploratory clinical study designed to evaluate the feasibility, safety, and clinical utility of ^68Ga-grazytracer positron emission tomography (PET) for noninvasive in vivo visualization of immune cell effector function in patients with cancer and autoimmune diseases. ^68Ga-grazytracer is a granzyme B (GZMB)-targeted PET radiotracer developed to visualize cytotoxic immune activation.
Approximately 60-80 adult participants will be enrolled in two study cohorts: (1) patients with malignant tumors who are scheduled to receive systemic anticancer therapy, including immune checkpoint inhibitors, CAR-T cell therapy, chemotherapy, radiotherapy, targeted therapy, or combination therapy; and (2) patients with autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, and immune myocarditis, who are receiving or planning to receive immunomodulatory treatment.
Participants will undergo ^68Ga-grazytracer PET/CT imaging before treatment initiation and again during the predefined treatment period. Imaging findings, including tracer uptake and semiquantitative parameters (e.g., SUVmax and target-to-background ratio), will be analyzed together with clinical outcomes, laboratory findings, disease activity assessments, and follow-up data.
The primary objectives are to evaluate the safety and tolerability of ^68Ga-grazytracer PET imaging and to investigate the association between GZMB-targeted PET imaging and treatment response in patients with cancer, disease activity and organ involvement in autoimmune diseases, and therapeutic response to immunomodulatory treatment. This study aims to provide preliminary evidence supporting the use of ^68Ga-grazytracer PET as a molecular imaging biomarker for noninvasive assessment of immune effector function in cancer and autoimmune diseases.
Aperçu de l'étude
Statut
Intervention / Traitement
Description détaillée
Background Granzyme B (GZMB) is a key effector molecule released by activated cytotoxic T lymphocytes and natural killer cells during immune responses. GZMB-mediated cytotoxic activity plays an important role in antitumor immunity and is also involved in tissue injury, immune remodeling, and therapeutic responses in autoimmune diseases. Therefore, noninvasive visualization of GZMB activity may provide a direct assessment of immune effector function in vivo.
^68Ga-grazytracer is a GZMB-targeted PET radiotracer developed for molecular imaging of immune effector activity. Previous preclinical and early clinical studies have demonstrated the feasibility of this tracer for monitoring immune responses and predicting treatment outcomes in patients receiving immunotherapy. However, its clinical value across different disease settings has not been systematically evaluated.
Objectives This study aims to investigate the clinical utility of ^68Ga-grazytracer PET for evaluating immune cell effector function in patients with cancer and autoimmune diseases. The specific objectives are:To evaluate the association between ^68Ga-grazytracer PET findings and treatment response in patients receiving cancer immunotherapy.To investigate the relationship between tracer uptake and disease activity, organ involvement, and therapeutic response in patients with autoimmune diseases.To evaluate the safety, tolerability, and imaging feasibility of ^68Ga-grazytracer PET.
Study Design This is a prospective, single-center, exploratory clinical study conducted at Peking University Third Hospital. Approximately 60-80 adult participants will be enrolled in two cohorts:a cancer cohort including patients with malignant tumors receiving systemic anticancer therapy; and an autoimmune disease cohort including patients with systemic lupus erythematosus, systemic sclerosis, or immune myocarditis receiving immunomodulatory therapy.
Participants will undergo ^68Ga-grazytracer PET/CT imaging before treatment initiation and again during the predefined treatment period. PET imaging findings will be analyzed together with clinical outcomes, laboratory biomarkers, disease activity assessments, and follow-up data to evaluate the relationship between GZMB-targeted imaging and immune responses.
Outcome Assessment Imaging analyses will include visual assessment and semiquantitative parameters such as maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR). The study will evaluate the relationship between PET imaging findings and treatment response, disease activity, organ involvement, and clinical outcomes. Safety assessments will include monitoring of tracer-related adverse events and overall tolerability.
Significance This study is expected to provide preliminary evidence supporting the use of ^68Ga-grazytracer PET as a noninvasive molecular imaging biomarker for immune cell effector function. The results may facilitate treatment response assessment in cancer immunotherapy and improve evaluation of disease activity and immune modulation in autoimmune diseases, thereby providing a foundation for future multicenter validation studies.
Type d'étude
Inscription (Estimé)
Phase
- N'est pas applicable
Contacts et emplacements
Coordonnées de l'étude
- Nom: Meixin Zhao
- Numéro de téléphone: 86-10-82264936
- E-mail: zhaomeixin.student@sina.com
Lieux d'étude
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Beijing Municipality
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Beijing, Beijing Municipality, Chine, 100191
- Recrutement
- Peking University Third Hospital
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Contact:
- Meixin Zhao
- Numéro de téléphone: 86-10-82264936
- E-mail: zhaomeixin.student@sina.com
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
**Inclusion Criteria:**
- Age ≥18 years, regardless of sex.
- Ability to understand the study objectives and provide written informed consent.
- Cancer cohort:
- Patients with a confirmed diagnosis of malignancy who are scheduled to receive systemic anticancer treatment.
- Patients who have not previously received immunotherapy.
- Autoimmune disease cohort:
- Patients with a confirmed diagnosis of an autoimmune disease, such as systemic sclerosis or systemic lupus erythematosus, with evidence of immune-mediated inflammation.
- Patients who are scheduled to receive or are currently receiving immunomodulatory therapy.
**Exclusion Criteria:**
- Pregnant or breastfeeding women.
- Patients with severe cardiac, hepatic, renal, or other major organ dysfunction who are considered unsuitable for study participation by the investigator.
- Patients unable to tolerate PET/CT imaging or complete the required follow-up assessments.
- Patients with any other condition that, in the investigator's judgment, makes them unsuitable for participation in the study.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Diagnostique
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: ^68Ga-grazytracer PET Imaging
All enrolled participants will undergo ^68Ga-grazytracer PET/CT imaging according to the study protocol for noninvasive assessment of immune cell effector function. Participants include patients with cancer and autoimmune diseases. PET/CT imaging will be performed before treatment initiation and during the predefined treatment period according to the study protocol. Imaging findings will be correlated with clinical characteristics, treatment response, and disease activity. |
Participants will undergo whole-body ^68Ga-grazytracer PET/CT imaging following intravenous administration of ^68Ga-grazytracer according to the study protocol. PET/CT imaging will be performed before treatment initiation and during the predefined treatment period to noninvasively assess granzyme B expression and immune cell effector function in vivo. Imaging findings will be analyzed in conjunction with clinical characteristics, treatment response, disease activity, and other study assessments. |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Incidence of Adverse Events Related to ⁶⁸Ga-grazytracer PET/CT Imaging
Délai: From tracer administration through completion of PET/CT imaging (approximately 2 hours).
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The number and percentage of participants experiencing adverse events (AEs) related to ⁶⁸Ga-grazytracer administration or PET/CT imaging will be assessed. Adverse events will be evaluated according to their occurrence, severity (CTCAE grade), and relationship to the imaging procedure, including serious adverse events (SAEs). |
From tracer administration through completion of PET/CT imaging (approximately 2 hours).
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Change in Maximum Standardized Uptake Value (SUVmax) on ⁶⁸Ga-grazytracer PET
Délai: Baseline and during the predefined treatment period (up to 6 months).
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The maximum standardized uptake value (SUVmax) will be measured in predefined target lesions or affected tissues using ⁶⁸Ga-grazytracer PET imaging. Changes in SUVmax from baseline to follow-up will be assessed to characterize granzyme B-related immune activity during treatment. |
Baseline and during the predefined treatment period (up to 6 months).
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Change in Target-to-Background Ratio (TBR) on ⁶⁸Ga-grazytracer PET
Délai: Baseline and during the predefined treatment period (up to 6 months).
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The target-to-background ratio (TBR) will be calculated for predefined target lesions or affected tissues using ⁶⁸Ga-grazytracer PET imaging, with a predefined reference region such as the blood pool or liver. Changes in TBR from baseline to follow-up will be assessed to characterize relative tracer uptake during treatment. TBR is a dimensionless ratio. |
Baseline and during the predefined treatment period (up to 6 months).
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Area Under the ROC Curve (AUC) of ⁶⁸Ga-grazytracer PET SUVmax for Predicting Tumor Treatment Response
Délai: Up to 6 months
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The discriminative performance of ⁶⁸Ga-grazytracer PET maximum standardized uptake value (SUVmax) for distinguishing treatment responders from non-responders will be evaluated in the cancer cohort using receiver operating characteristic (ROC) curve analysis. Tumor response will be assessed according to RECIST 1.1 or iRECIST criteria, with responders defined as complete response (CR) or partial response (PR), and non-responders as stable disease (SD) or progressive disease (PD). The area under the ROC curve (AUC), a dimensionless measure ranging from 0 to 1, will be reported with its 95% confidence interval. |
Up to 6 months
|
Collaborateurs et enquêteurs
Parrainer
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Métabolisme, erreurs innées
- Maladies génétiques, innées
- Maladies métaboliques
- Maladies du tissu conjonctif
- Maladies du système immunitaire
- Maladies de la peau
- Troubles du métabolisme lipidique
- Métabolisme des lipides, erreurs innées
- Maladies de la peau, métabolisme
- Maladies et anomalies congénitales, héréditaires et néonatales
- Maladies nutritionnelles et métaboliques
- Maladies de la peau et du tissu conjonctif
- Lipodystrophie
- Tumeurs
- Lupus érythémateux systémique
- Maladies auto-immunes
- Sclérodermie systémique
- Lipodystrophie congénitale généralisée
Autres numéros d'identification d'étude
- IRB00006761-M20260118
Plan pour les données individuelles des participants (IPD)
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Informations sur les médicaments et les dispositifs, documents d'étude
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