^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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Meixin Zhao
- 電話番号：86-10-82264936
- メール：zhaomeixin.student@sina.com
研究場所
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Beijing Municipality
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Beijing、Beijing Municipality、中国、100191
- 募集
- Peking University Third Hospital
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コンタクト：
- Meixin Zhao
- 電話番号：86-10-82264936
- メール：zhaomeixin.student@sina.com
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-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
**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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：診断
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：^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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Incidence of Adverse Events Related to ⁶⁸Ga-grazytracer PET/CT Imaging
時間枠：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
時間枠：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
時間枠：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).
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Area Under the ROC Curve (AUC) of ⁶⁸Ga-grazytracer PET SUVmax for Predicting Tumor Treatment Response
時間枠：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
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協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
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本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- IRB00006761-M20260118
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