Related Experiment Video
Updated: Dec 31, 2025
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Synthesis and Application of a Long-Circulating Radiolabeled Peptide for Targeting of Osteosarcoma
Yesen Li1,2, Daifeng Li2,3, Hua Wu1
1Department of Nuclear Medicine and Minnan PET Center, Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China.
Purpose:
The small peptide TMTP1 (NVVRQ) has been proved to target a series of highly metastatic tumor cells. The aim of this study was to develop a new agent based on TMTP1 conjugated with Evans blue (EB), to increase tumor uptake and modify the pharmacokinetic characteristics of the resulting radiolabeled agent.
Procedures:
DOTA-EB-TMTP1 was prepared through conventional solid-phase peptide synthesis chemistry. Then, it was successfully labeled with Cu-64 to obtain [64Cu]DOTA-EB-TMTP1. The tumor targeting properties were evaluated in vivo using 143B xenografts.
Results:
DOTA-EB-TMTP1 was successfully labeled with Cu-64 in a yield of 87.3 ± 5.2 %. In a small animal positron emission tomography/X-ray computed tomography (PET/CT) study in osteosarcoma 143B xenograft mice, [64Cu]DOTA-EB-TMTP1 was found to rapidly accumulate in the tumor tissue. The tumor uptake increased over time and reached a plateau of 6.50 ± 0.88 % ID/g 8 h after tail vein injection. The radioactivity remained in the tumor tissue 48 h postinjection with a negligible decrease.
Conclusions:
Overall, the introduction of the EB motif to TMTP1 significantly changed its pharmacokinetics in vivo, and this strategy fulfills the purpose of prolonging the blood circulation and enhancing the tumor uptake. [64Cu]DOTA-EB-TMTP1 is a promising agent for osteosarcoma targeting. Moreover, our study highlights that DOTA-EB-TMTP1 is a good candidate for labeling with different radionuclides for potential theranostic applications.
Insights
A new radiolabeled agent, [64Cu]DOTA-EB-TMTP1, enhances tumor uptake and prolongs circulation for osteosarcoma targeting. This peptide-drug conjugate shows promise for theranostic applications.
Area of Science:
- Biomedical imaging
- Radiochemistry
- Oncology
Background:
- The peptide TMTP1 targets metastatic tumors.
- Developing targeted radiolabeled agents is crucial for cancer imaging and therapy.
Purpose of the Study:
- To create a novel agent by conjugating TMTP1 with Evans blue (EB).
- To enhance tumor uptake and modify pharmacokinetics of a radiolabeled TMTP1-based agent.
Main Methods:
- Synthesis of DOTA-EB-TMTP1 via solid-phase peptide synthesis.
- Radiolabeling with Copper-64 (64Cu) to form [64Cu]DOTA-EB-TMTP1.
- In vivo evaluation of tumor targeting in 143B xenografts using PET/CT.
Main Results:
- Successful radiolabeling of DOTA-EB-TMTP1 with 64Cu achieved 87.3% yield.
- [64Cu]DOTA-EB-TMTP1 rapidly accumulated in osteosarcoma tumors.
- Tumor uptake reached 6.50% ID/g at 8 hours and remained high at 48 hours post-injection.
Conclusions:
- Conjugating EB to TMTP1 improved pharmacokinetics, increasing blood circulation and tumor uptake.
- [64Cu]DOTA-EB-TMTP1 is a promising agent for osteosarcoma targeting.
- DOTA-EB-TMTP1 is suitable for labeling with various radionuclides for theranostic use.
