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MR Molecular Imaging of Prostate Cancer with a Small Molecular CLT1 Peptide Targeted Contrast Agent
Published on: September 3, 2013
First-in-Class CD146-Targeting Peptide Probes for Noninvasive PET Imaging of Melanoma
Qian Zhang1,2, Xiaoyi Guo2, Siqi Hao1,2
1GuiZhou University Medical College , Guiyang550025, Guizhou Province, China.
Abstract:
The transmembrane glycoprotein CD146, overexpressed in solid tumors and tumor vasculature, is a compelling target reinforced by CD146-targeting antibody-drug conjugates (ADCs) in clinical trials. This development underscores the unmet need for noninvasive imaging tools to guide patient selection. Here, we report the first [68Ga]Ga-labeled peptide-based molecular imaging agents targeting CD146: [68Ga]Ga-DOTA-P1 and [68Ga]Ga-DOTA-P2. Both probes were reliably synthesized with radiochemical yield >90% within 15 min and radiochemical purity exceeding 95% (n = 5). [68Ga]Ga-DOTA-P1 and [68Ga]Ga-DOTA-P2 have good in vitro stability, and high affinity for CD146-positive cell, with Kd values of 152.3 nM and 205.1 nM, respectively. In vitro cellular assays demonstrated specific binding, and fluorescence imaging with the analog FITC-P1 visually confirmed robust CD146-mediated cellular uptake. In vivo PET/CT imaging demonstrated rapid tumor uptake and tissue excretion. A375 model showed a higher tumor-to-muscle ratio (5.33 ± 0.58) with [68Ga]Ga-DOTA-P1 at 30 min, whereas [68Ga]Ga-DOTA-P2 produced lower contrast (2.55 ± 0.58) due to its slower blood clearance; in addition, the imaging ability of [68Ga]Ga-DOTA-P1 was also verified in another CD146-positive model (SK-Mel-28). An immunohistochemical test was performed to assess CD146 distribution, showing low expression in normal tissues versus positive membrane-localized expression in A375 and SK-Mel-28 tumors. This work establishes [68Ga]Ga-DOTA-P1 as a rapid, high-contrast imaging tool for CD146-expressing malignancies, offering a practical strategy for noninvasive patient stratification in the era of targeted CD146 therapies.
Insights
Researchers developed novel [68Ga]Ga-labeled peptide imaging agents, [68Ga]Ga-DOTA-P1 and [68Ga]Ga-DOTA-P2, to target CD146. [68Ga]Ga-DOTA-P1 demonstrated rapid tumor uptake and high contrast for noninvasive imaging of CD146-expressing cancers.
Area of Science:
- Molecular Imaging
- Oncology
- Radiochemistry
Background:
- CD146 is a transmembrane glycoprotein overexpressed in solid tumors and tumor vasculature.
- CD146-targeting antibody-drug conjugates are in clinical trials, highlighting the need for noninvasive imaging tools.
- Current imaging methods lack specificity and sensitivity for guiding patient selection in CD146-targeted therapies.
Purpose of the Study:
- To develop and evaluate novel peptide-based positron emission tomography (PET) imaging agents targeting CD146.
- To assess the synthesis, stability, affinity, and in vitro/in vivo performance of [68Ga]Ga-labeled DOTA-conjugated peptides (P1 and P2).
- To establish a noninvasive imaging strategy for patient stratification in CD146-targeted cancer therapy.
Main Methods:
- Synthesis and radiolabeling of [68Ga]Ga-DOTA-P1 and [68Ga]Ga-DOTA-P2 with high radiochemical yield and purity.
- In vitro evaluation of probe stability, binding affinity (Kd), and cellular uptake in CD146-positive cells.
- In vivo preclinical evaluation using PET/CT imaging in CD146-positive tumor models (A375 and SK-Mel-28).
- Immunohistochemical analysis to confirm CD146 expression in tumor tissues.
Main Results:
- Both [68Ga]Ga-DOTA-P1 and [68Ga]Ga-DOTA-P2 were synthesized efficiently (>90% yield, >95% purity) and exhibited good in vitro stability.
- [68Ga]Ga-DOTA-P1 showed high affinity (Kd = 152.3 nM) and specific binding to CD146-positive cells, with robust CD146-mediated uptake.
- In vivo PET/CT imaging revealed rapid tumor uptake and efficient tissue excretion for [68Ga]Ga-DOTA-P1, achieving a high tumor-to-muscle ratio (5.33 ± 0.58) in the A375 model at 30 min.
- [68Ga]Ga-DOTA-P1 demonstrated effective imaging in both A375 and SK-Mel-28 CD146-positive tumor models.
Conclusions:
- [68Ga]Ga-DOTA-P1 is a promising molecular imaging agent for rapid, high-contrast detection of CD146-expressing malignancies.
- This agent offers a practical noninvasive strategy for patient stratification in the context of CD146-targeted therapies.
- The development represents a significant advancement in molecular imaging for precision oncology.
