Emerging ImmunoPET probes for precision cancer immunotherapy: molecular targets and translational applications

Area of Science:

• Oncology
• Immunology
• Molecular Imaging

Background:

• Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but predicting patient response remains challenging.
• Current stratification tools like biopsy and PD-L1 IHC fail to capture tumor immune microenvironment heterogeneity.
• Positron emission tomography (PET) with radiolabeled antibodies (ImmunoPET) offers a non-invasive, whole-body approach.

Purpose of the Study:

• To review the biological rationale and translational status of ImmunoPET for mapping immune checkpoints in cancer.
• To explore ImmunoPET's potential in predicting treatment outcomes across various cancer types.
• To discuss probe engineering, theranostic applications, and radiomics in ImmunoPET.

Main Methods:

• Review of existing literature on ImmunoPET targets, including inhibitory (PD-1/PD-L1, CTLA-4) and co-stimulatory receptors.
• Examination of probe engineering principles (scaffold, radionuclide, pretargeting).
• Analysis of clinical data comparing ImmunoPET metrics with immunohistochemistry (IHC) for treatment outcome prediction.

Main Results:

• Whole-body ImmunoPET metrics demonstrate superior prediction of treatment outcomes compared to concurrent IHC.
• Clinical evidence supports ImmunoPET's utility across thoracic, genitourinary, hematological, and neuro-oncological malignancies.
• ImmunoPET enables non-invasive mapping of immune checkpoint expression across the entire disease burden, addressing spatial heterogeneity.

Conclusions:

• ImmunoPET is a promising tool for overcoming limitations of current stratification methods in oncology.
• Standardization of quantitative thresholds and acquisition protocols is crucial for regulatory approval.
• ImmunoPET holds potential as a companion diagnostic for guiding ICI therapy.