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Updated: Jan 11, 2026
![Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F68356.jpg&w=3840&q=50)
Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
Novel dimeric dual-modality FAP-targeted agents with favorable tumor retention for image-guided surgery: a
Giacomo Gariglio1, Thomas Hasenöhrl2, Katerina Bendova3
1Department of Nuclear Medicine, Medical University of Innsbruck, 6020, Innsbruck, Austria.
Purpose:
Complete and minimally invasive cancer surgery remains challenging. Targeting the fibroblast activation protein (FAP) offers valuable opportunities for surgical planning, intraoperative guidance and improved resection outcomes. Herein, we developed the first dimeric, dual-modality FAP-targeted imaging agents and investigated the influence of different near-infrared cyanine-7 dyes on their final properties.
Methods:
Four dual-modality ligands based on the Fusarinine C scaffold were synthesized. Their FAP specificity and retention were evaluated in cellular and xenograft tumor models. The most promising candidates were labelled with 67/68Ga and assessed in vivo at early time points by PET/CT imaging and by comparative SPECT/CT and NIR fluorescence imaging (FI) up to two days post-injection.
Results:
Distinct fluorophore influences on the properties of the final compounds were identified. The introduction of the s775z dye demonstrated a beneficial effect on the cellular uptake and on the in vivo biodistribution profile as revealed by the greatest improvement in blood clearance and the least off-target accumulation in liver and kidneys when compared to the control and to the other candidates respectively. Ex vivo experiments and in vivo PET/CT, SPECT/CT and FI studies in xenografted mice confirmed these findings and demonstrated sustained tumor uptake (> 7% ID/g and > 5% ID/g at 1 h and 1 day p.i. respectively) for 67Ga-s775z-FFAPi and 67Ga-IRDye-FFAPi.
Conclusions:
In this study we introduced and evaluated novel dimeric FAP-targeting agents for dual-modality applications. In the preclinical setting, within the group of compounds investigated, two candidates enabled tumor visualization through PET, SPECT and optical imaging, providing satisfactory background contrast after a single administration and supporting their potential for preoperative nuclear imaging and subsequent fluorescence-guided surgery.
Insights
Novel dimeric fibroblast activation protein (FAP) imaging agents were developed. The s775z dye enhanced uptake and reduced off-target accumulation, showing promise for dual-modality cancer surgery guidance.
Area of Science:
- Oncology
- Radiochemistry
- Medical Imaging
Background:
- Complete and minimally invasive cancer surgery requires improved tools for planning and guidance.
- Targeting fibroblast activation protein (FAP) is a promising strategy for enhancing surgical outcomes.
- Developing dual-modality imaging agents offers potential for comprehensive intraoperative visualization.
Purpose of the Study:
- To develop novel dimeric, dual-modality fibroblast activation protein (FAP)-targeted imaging agents.
- To investigate the influence of different near-infrared cyanine-7 dyes on the properties of these agents.
- To evaluate the potential of these agents for surgical planning and intraoperative guidance.
Main Methods:
- Synthesis of four dual-modality ligands based on the Fusarinine C scaffold.
- Evaluation of FAP specificity and retention in cellular and xenograft tumor models.
- Labeling promising candidates with 67/68Ga and in vivo assessment using PET/CT, SPECT/CT, and NIR fluorescence imaging.
Main Results:
- The s775z dye incorporation improved cellular uptake and in vivo biodistribution, enhancing blood clearance and reducing off-target accumulation.
- PET/CT, SPECT/CT, and fluorescence imaging demonstrated sustained tumor uptake for 67Ga-s775z-FFAPi and 67Ga-IRDye-FFAPi.
- Two dimeric FAP-targeting agents provided satisfactory tumor visualization with good background contrast.
Conclusions:
- Novel dimeric FAP-targeting agents were successfully developed and evaluated for dual-modality applications.
- The s775z-containing agent demonstrated superior properties for in vivo imaging.
- These agents show potential for preoperative nuclear imaging and fluorescence-guided surgery in preclinical models.
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