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

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.