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Updated: Aug 29, 2026
Preparing a 68Ga-labeled Arginine Glycine Aspartate (RGD)-peptide for Angiogenesis
Published on: January 7, 2019
MicroPET and autoradiographic imaging of breast cancer alpha v-integrin expression using 18F- and 64Cu-labeled RGD
Xiaoyuan Chen1, Ryan Park, Michel Tohme
1PET Imaging Science Center, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA.
Abstract:
Cell adhesion molecules alphavbeta3 and alphavbeta5 play a pivotal role in tumor angiogenesis and metastasis. Antiangiogenic therapy by using small peptide antagonists of alphav-integrins slows tumor growth and prevents tumor spread. The ability to visualize and quantify integrin expression will enable selection of appropriate patients for clinical trials, following determination of treatment efficacy and development of new potent drugs. We have previously labeled cyclic RGD peptide c(RGDyK) with 125I and 18F and applied the radiotracers to both subcutaneous and orthotopic brain tumor models. Here we conjugated c(RGDyK) with 1,4,7,10-tetraaza-1,4,7,10-tetradodecane-N,N',N' ',N' "-tetraacetic acid (DOTA) and labeled the DOTA-RGD conjugate with 64Cu (t1/2) = 12.8 h, 19% beta+) in high radiochemical purity and specific activity. The tumor targeting ability and in vivo kinetics of 64Cu-DOTA-RGD was compared with [18F]FB-RGD and 125I-RGD in orthotopic MDA-MB-435 breast cancer model. All three radiotracers revealed fast blood clearance and high tumor-to-blood and tumor-to-muscle ratios. 125I-RGD had higher tumor uptake than the corresponding 18F and 64Cu analogues. [18F]FB-RGD indicated a fast tumor washout rate and an unfavorable hepatobiliary excretion pathway, resulting in significant activity accumulation in gallbladder and intestines. 64Cu-DOTA-RGD had prolonged tumor retention (1.44 +/- 0.09 %ID/g at 4 h postinjection) and persistent uptake in the liver. All three tracers revealed receptor specific tumor accumulation which were illustrated by effective blocking via coinjection with a blocking dose of c(RGDyK). Static microPET imaging and whole-body autoradiography showed strong contrast from the contralateral background. In conclusion, overall molecular charge and characteristics of radiolabels have profound effects on tumor accumulation and in vivo kinetics of radiolabeled RGD peptide. Further modification of the RGD peptide and optimization of the tracer for prolonged tumor uptake and improved in vivo kinetics are being explored.
Insights
Researchers compared three radiotracers for imaging integrin expression in breast cancer. 64Cu-DOTA-RGD showed prolonged tumor retention, offering potential for improved cancer diagnostics and targeted therapies.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Integrins alphavbeta3 and alphavbeta5 are key in tumor growth and spread.
- Antiangiogenic therapy targeting integrins shows promise but requires effective patient selection and monitoring.
- Visualizing integrin expression is crucial for clinical trials and drug development.
Purpose of the Study:
- To evaluate and compare the tumor targeting and in vivo kinetics of three RGD-based radiotracers: 125I-RGD, [18F]FB-RGD, and 64Cu-DOTA-RGD.
- To assess their potential for imaging integrin expression in orthotopic breast cancer models.
Main Methods:
- Conjugation of cyclic RGD peptide c(RGDyK) with DOTA and subsequent labeling with 64Cu.
- Comparison of 64Cu-DOTA-RGD with [18F]FB-RGD and 125I-RGD in an orthotopic MDA-MB-435 breast cancer model.
- Analysis of tumor uptake, blood clearance, biodistribution, and blocking studies using microPET imaging and autoradiography.
Main Results:
- All three radiotracers demonstrated fast blood clearance and favorable tumor-to-background ratios.
- 125I-RGD exhibited higher tumor uptake compared to 18F and 64Cu analogues.
- [18F]FB-RGD showed rapid tumor washout and unfavorable hepatobiliary excretion, while 64Cu-DOTA-RGD displayed prolonged tumor retention with persistent liver uptake.
Conclusions:
- Radiotracer characteristics, including molecular charge and radiolabel properties, significantly influence tumor accumulation and in vivo kinetics.
- 64Cu-DOTA-RGD demonstrates promising prolonged tumor retention for potential use in molecular imaging.
- Further optimization of RGD peptide tracers is warranted to enhance tumor uptake and improve in vivo behavior for diagnostic and therapeutic applications.
