Evaluating Ga-68 Peptide Conjugates for Targeting VPAC Receptors: Stability and Pharmacokinetics
Pardeep Kumar1, Sushil K Tripathi1, C P Chen2
1Departments of Radiology, Thomas Jefferson University, Philadelphia, PA, USA.
Molecular Imaging and Biology
|May 27, 2018
Summary
Gallium-68 labeled NODAGA-peptide shows superior tumor imaging compared to DOTA-peptide for detecting breast cancer (BC) via positron emission tomography/computed tomography (PET/CT). Despite lower in vivo stability, NODAGA-peptide offers better tumor-to-muscle ratios, aiding oncologic disease visualization.
Area of Science:
- Radiopharmaceutical chemistry
- Molecular imaging
- Oncology
Background:
- Gallium-68 (Ga-68) labeled peptides are advancing oncologic disease imaging.
- Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) receptors are targets on tumor cells.
Purpose of the Study:
- To evaluate the stability and pharmacokinetics of Ga-68 labeled NODAGA and DOTA-peptide conjugates targeting VPAC receptors.
- To compare their efficacy in imaging breast cancer (BC) xenografts.
Main Methods:
- Peptide synthesis and conjugation to NODAGA and DOTA chelators.
- Radiolabeling with Ga-68 and assessment of radiochemical purity.
- In vitro and in vivo stability studies in plasma, urine, and tumor-bearing mice.
- Cell binding assays and positron emission tomography/computed tomography (PET/CT) imaging.
Main Results:
- Both conjugates demonstrated high chemical and radiochemical purity (>95%) and stability against transchelation/transmetallation.
- [68Ga]NODAGA-peptide exhibited significantly higher specific binding to BT474 breast cancer cells (53.9%) compared to [68Ga]DOTA-peptide (25.8%).
- PET/CT imaging revealed a superior tumor-to-muscle ratio for [68Ga]NODAGA-peptide (3.4) versus [68Ga]DOTA-peptide (1.8).
Conclusions:
- NODAGA offers faster radiolabeling kinetics and higher specific activity compared to DOTA.
- While both conjugates show limited in vivo stability, [68Ga]NODAGA-peptide effectively delineates breast cancer tumors in PET/CT imaging, outperforming [68Ga]DOTA-peptide.
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