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Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
Synthesis and In Vivo and In Vitro Properties of 99mTc-Labeled Fibroblast Activation Protein Inhibitors
Sufan Tang1,2,3, Zhicong Yang1,2,3, Jiaqi Nie1,2,3
1Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou, Sichuan 646000, China.
Abstract:
Fibroblast activation protein (FAP) is expressed in more than 90% of tumor-associated fibroblasts in epithelial cancers, providing an excellent target for nuclear medicine diagnostics and therapy. Given the high cost of PET-CT, developing SPECT probes targeting FAP is necessary. A novel FAP inhibitor derived from UAMC1110 was synthesized and conjugated to DOTA via PEG chains. This resulted in a series of inhibitors with good targeting specificity, tumor uptake, and pharmacokinetics. In this study, UAMC1110 derivatives were used as FAP-targeting pharmacophores; PEG chains of varying lengths were employed for pharmacokinetic modification, and HYNIC was used as a bifunctional chelator. The derivatives were labeled with 99mTc using different coligand combinations to explore how PEG chain length and coligand composition affect the in vivo and in vitro properties of 99mTc-labeled FAPI. Four UAMC1110 derivatives (P4, P6, P8, P12) with different PEG chain lengths were synthesized, and a series of hydrophilic 99mTc complexes were prepared. Stability and specificity studies demonstrated that these complexes exhibited good in vitro and in vivo stability and FAP-targeting specificity. In micro-SPECT imaging, these tracers showed rapid tumor accumulation, with 99mTc-TE-P12 and 99mTc-TT-P12 showing promising tumor uptake, low nontarget organ uptake, and high T/NT ratios, indicating potential as SPECT probes.
Insights
Developing novel technetium-99m labeled probes targeting fibroblast activation protein (FAP) is crucial for cancer diagnostics. Researchers synthesized and evaluated new FAP inhibitors, identifying promising SPECT tracers with good tumor uptake and specificity.
Area of Science:
- Nuclear Medicine
- Radiochemistry
- Oncology
Background:
- Fibroblast activation protein (FAP) is highly expressed in epithelial cancers, making it a prime target for nuclear imaging.
- Positron Emission Tomography-Computed Tomography (PET-CT) is effective but costly; therefore, Single Photon Emission Computed Tomography (SPECT) probes are needed.
- Developing cost-effective SPECT agents targeting FAP can improve cancer diagnostics.
Purpose of the Study:
- To synthesize and characterize novel 99mTc-labeled fibroblast activation protein inhibitors (FAPI) for SPECT imaging.
- To investigate the impact of polyethylene glycol (PEG) chain length and coligand composition on the properties of 99mTc-FAPI.
- To evaluate the in vitro and in vivo performance of these novel SPECT probes.
Main Methods:
- Synthesis of UAMC1110 derivatives with varying PEG chain lengths.
- Labeling of derivatives with 99mTc using HYNIC as a bifunctional chelator and different coligands.
- In vitro stability and specificity assays against FAP.
- In vivo micro-SPECT imaging in tumor-bearing models to assess tumor uptake and biodistribution.
Main Results:
- Four 99mTc-labeled FAPI derivatives (P4, P6, P8, P12) were successfully prepared with good hydrophilicity.
- The complexes demonstrated excellent in vitro and in vivo stability and high specificity for FAP.
- Micro-SPECT imaging revealed rapid tumor accumulation, with 99mTc-TE-P12 and 99mTc-TT-P12 showing high tumor uptake and low off-target accumulation.
Conclusions:
- 99mTc-TE-P12 and 99mTc-TT-P12 exhibit promising characteristics as SPECT imaging agents for FAP-targeted cancer diagnostics.
- These novel tracers offer a potential cost-effective alternative to PET-based imaging for FAP-expressing tumors.
- Further investigation is warranted to explore their full clinical potential in nuclear medicine.
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