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In Vivo Interrogation of Cell-Penetrating Peptide Function: Accumulation in Tumors and the Potential as a Specific
Zhan Si1,2, Lulu Tian3, Hongxin Zhou4
1Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Abstract:
We aimed to evaluate the biodistribution and specificity of 68Ga-DOTA-TAT and RHO-TAT using MGC-803 and HT-29 tumor cells as well as tumor-xenografted nude mice and to demonstrate its application in positron emission tomography (PET) imaging. The in vitro evaluation of 68Ga-DOTA-TAT was assessed in MGC-803 and HT-29 cell lines, and the in vivo evaluation of 68Ga-DOTA-TAT was also performed in mice bearing MGC-803 or HT-29 tumors, respectively. Fluorescence microscopy was also employed to evaluate the specificity of RHO-TAT in vitro in MGC-803 and HT-29 cells as well as ex vivo in tumor slices of the corresponding tumor models. The in vivo imaging differences between 68Ga-DOTA-TAT and 18F-FDG in MGC-803 and HT-29 tumors were also studied. The biodistribution and micro-PET results demonstrated significant uptake of 68Ga-DOTA-TAT in non-FDG-avid MGC-803 tumors, whereas there was negligible uptake in FDG-avid HT-29 tumors. RHO-TAT showed superior fluorescence microscopy imaging effects in MGC-803 cells and tumor slices but not in HT-29 cells and tumor slices, which were consistent with the in vivo results. 68Ga-DOTA-TAT combined with 18F-FDG can be applied noninvasively in cancers with PET imaging for potential patient selection and stratification. We demonstrated a higher binding of 68Ga-DOTA-TAT and RHO-TAT to MGC-803 cells as well as to non-FDG-avid MGC-803 xenografted tumors and a lower binding to HT-29 cells and FDG-avid xenografted tumors. These results suggest that TAT has the potential to be a ligand for targeting certain tumors.
Insights
This study shows that 68Ga-DOTA-TAT and RHO-TAT target MGC-803 tumors but not HT-29 tumors. This peptide (TAT) shows potential for positron emission tomography (PET) imaging in specific cancer types.
Area of Science:
- Nuclear Medicine
- Molecular Imaging
- Oncology
Background:
- Targeted molecular imaging agents are crucial for cancer diagnosis and treatment selection.
- The peptide TAT (transporter of activated transcription) has shown potential for tumor targeting.
- Evaluating novel radiotracers like 68Ga-DOTA-TAT and fluorescent probes like RHO-TAT is essential for advancing PET imaging.
Purpose of the Study:
- To assess the biodistribution and specificity of 68Ga-DOTA-TAT and RHO-TAT in preclinical cancer models.
- To investigate the utility of 68Ga-DOTA-TAT for positron emission tomography (PET) imaging.
- To compare the tumor uptake of 68Ga-DOTA-TAT with 18F-FDG in different tumor types.
Main Methods:
- In vitro studies using MGC-803 and HT-29 cell lines to evaluate 68Ga-DOTA-TAT and RHO-TAT binding.
- In vivo biodistribution and micro-PET imaging of 68Ga-DOTA-TAT in mice bearing MGC-803 or HT-29 xenografts.
- Fluorescence microscopy of RHO-TAT in cells and ex vivo tumor slices to confirm specificity.
Main Results:
- 68Ga-DOTA-TAT demonstrated significant uptake in non-FDG-avid MGC-803 tumors but negligible uptake in FDG-avid HT-29 tumors.
- RHO-TAT showed superior fluorescence imaging in MGC-803 cells and tumors, consistent with 68Ga-DOTA-TAT biodistribution.
- Binding was higher for MGC-803 cells and tumors, and lower for HT-29 cells and tumors, for both TAT-based agents.
Conclusions:
- The TAT peptide shows potential as a ligand for targeting specific tumor types, particularly non-FDG-avid ones.
- 68Ga-DOTA-TAT PET imaging can differentiate between tumor types based on tracer uptake.
- Combined use of 68Ga-DOTA-TAT and 18F-FDG PET may aid in cancer patient selection and stratification.
