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Immuno-Imaging (PET/SPECT)-Quo Vadis?

Carsten S Kramer1, Antonia Dimitrakopoulou-Strauss2

  • 1Curanosticum Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, D-65191 Wiesbaden, Germany.

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Summary
This summary is machine-generated.

Conventional methods struggle to assess immunotherapy response in cancer. This study analyzed 106 tracers, finding most target immune checkpoints; an orthogonal approach targeting intracellular molecules is suggested for improved patient stratification and treatment assessment.

Keywords:
PET/CTSPECT/CTcheckpoint inhibitorsdrug designimmuno-imagingimmunoPETimmunotherapymolecular imagingresponse criteriatumor microenvironment

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Area of Science:

  • Nuclear medicine
  • Radiochemistry
  • Immunology

Background:

  • Immunotherapy has transformed cancer treatment, but assessing patient response remains challenging with conventional imaging and criteria developed for chemotherapy.
  • Current methods like CT/MRT and FDG PET-CT, along with RECIST/PERCIST criteria, are insufficient for evaluating immunotherapy efficacy.
  • There is a critical need for improved imaging tracers to accurately assess treatment response and stratify patients in immunotherapy.

Purpose of the Study:

  • To analyze published SPECT/PET tracers for immunotherapy response assessment.
  • To classify tracers based on target choice, clinical developability, real-world translatability, and diagnostic quality.
  • To propose novel strategies for developing more effective imaging agents for immunotherapy.

Main Methods:

  • A comprehensive literature search identified 106 individual SPECT/PET tracers.
  • A descriptor-based analysis was performed to classify tracers.
  • Tracer characteristics including target, developability, translatability, and diagnostic quality were evaluated.

Main Results:

  • Most identified tracers target immune checkpoint receptors such as PD-L1, PD-1, CTLA-4, and CD8, often using antibodies or fragments.
  • A significant number of tracers represent minor modifications of existing agents (e.g., chelators, nuclides) rather than innovative approaches.
  • Current tracers show limited innovation, with many focusing on similar targets and methodologies.

Conclusions:

  • There is a need for more innovative tracer development in immunotherapy response assessment.
  • An orthogonal strategy focusing on underrepresented intracellular targets using PET-activatable small molecules could offer significant advantages.
  • This approach may lead to improved diagnostic quality and clinical utility for patient stratification in cancer immunotherapy.