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[68Ga]Ga-GZP PET for Early Response Prediction in Colorectal Cancer During Neoadjuvant Therapy

H

Huazhong University of Science and Technology

Status

Completed

Conditions

Colorectal Cancer Recurrent
Colorectal Cancer Control and Prevention
Colorectal Cancer Metastatic
Colorectal Cancer Screening

Treatments

Diagnostic Test: Received 68Ga-NOTA-GZP PET scanning

Study type

Interventional

Funder types

Other

Identifiers

NCT06982053
XLan-0506

Details and patient eligibility

About

This diagnostic study investigates the value of 68Ga-NOTA-GZP PET imaging in predicting and evaluating immunotherapy response in malignant tumors by enrolling pathologically confirmed patients scheduled for immunotherapy and healthy volunteers. All participants underwent immunohistochemical staining of tumor tissue for immune checkpoint markers (PD-1 or CTLA-4) and granzyme B expression prior to signing informed consent for 68Ga-NOTA-GZP PET imaging. Patients received baseline scans before initial immunotherapy and follow-up scans during treatment cycles 2-4, with clinical monitoring continuing until 6 months post-treatment, while healthy volunteers completed single scans with pharmacokinetic analysis through serial blood/urine sampling. Comprehensive data collection included demographic information, clinical characteristics, immunohistochemistry results, laboratory tests (blood routine, liver/kidney function), PET imaging findings, and other relevant imaging data, with treatment response ultimately assessed according to RECIST 1.1 and iRECIST criteria at the 6-month follow-up endpoint.

Full description

Malignant tumors represent one of the leading causes of mortality worldwide, posing a significant threat to human health, where early diagnosis and timely intervention can substantially improve clinical outcomes. In recent years, immunotherapy has emerged as a cornerstone in comprehensive cancer treatment, with immune checkpoint inhibitors (ICIs) serving as a primary therapeutic modality. ICIs function by targeting regulatory pathways of T cells, specifically through blockade of immune checkpoints to enhance cytotoxic T cell activity and thereby elicit anti-tumor immune responses. However, the clinical benefits remain limited to a subset of patients, with many eventually experiencing disease progression or recurrence. Given the heterogeneous response patterns observed during immunotherapy, early and dynamic treatment response assessment becomes paramount - early identification of responders versus non-responders enables timely stratification of patients to avoid ineffective treatments, while continuous monitoring allows for comprehensive evaluation of tumor response patterns to minimize unnecessary adverse effects.

The cytotoxic lymphocytes play a pivotal role in anti-tumor immunity, with granzyme B, a serine protease released by activated cytotoxic lymphocytes during immune responses, representing one of the two principal mechanisms through which lymphocytes mediate cancer cell apoptosis. The quantification of granzyme B directly reflects the activity status of cytotoxic lymphocytes. Compared to general immune cell infiltration assessments, measuring active immune cell populations provides a more precise indicator of immune response intensity and greater predictive value for immunotherapy outcomes. The development of 68Ga-NOTA-GZP, a 68Ga-labeled peptide specifically targeting granzyme B, enables non-invasive visualization of cytotoxic lymphocyte activity. This novel PET tracer shows potential for early differentiation between treatment responders and non-responders, facilitating prompt clinical decision-making to discontinue ineffective therapies.

Building upon the promising potential of 68Ga-NOTA-GZP in immunotherapy monitoring, this study aims to systematically evaluate its efficacy in predicting and assessing treatment responses in malignant tumors. Using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) and immune-modified RECIST (iRECIST) as reference standards, we will investigate the tracer's capability for early treatment response prediction and real-time monitoring, with the ultimate goals of accurately stratifying patients at the earliest timepoint and minimizing unnecessary immunotherapy-related toxicities.

Enrollment

21 patients

Sex

All

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Histologically confirmed treatment-naïve locally advanced rectal adenocarcinoma (T3-4N0M0 or T1-4N+M0)
  • No severe hematologic, cardiac, pulmonary, hepatic, or renal dysfunction
  • No immunodeficiency diseases
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Exclusion criteria

  • Prior anti-PD-1/PD-L1 antibody therapy
  • History of pelvic radiotherapy
  • Active autoimmune disease (excluding vitiligo and type 1 diabetes)
  • Hypersensitivity to monoclonal antibodies
  • History of interstitial lung disease
  • Active uncontrolled infection

Trial design

Primary purpose

Diagnostic

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

21 participants in 1 patient group

Received 68Ga-NOTA-GZP PET scanning
Experimental group
Treatment:
Diagnostic Test: Received 68Ga-NOTA-GZP PET scanning

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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