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Area of Science:

• Nuclear Medicine
• Oncology
• Radiochemistry

Background:

• N-cadherin is a key cell adhesion molecule and a therapeutic target in various cancers.
• The N-cadherin antagonist ADH-1 demonstrates significant antitumor activity.
• Developing targeted imaging agents for N-cadherin is crucial for cancer diagnosis and treatment monitoring.

Purpose of the Study:

• To develop and evaluate a novel positron emission tomography (PET) imaging probe, [18F]AlF-NOTA-ADH-1, for N-cadherin.
• To assess the in vitro and in vivo performance of [18F]AlF-NOTA-ADH-1 for targeting N-cadherin-expressing tumors.

Main Methods:

• Radiosynthesis of [18F]AlF-NOTA-ADH-1 with high radiochemical purity (>97%).
• In vitro cell binding assays using N-cadherin-expressing (SW480) and low-expressing (BXPC3) cancer cells.
• In vivo biodistribution studies and micro-PET imaging in patient-derived xenograft (PDX) and cell line-derived tumor models.
• Immunohistochemistry and blocking experiments to confirm N-cadherin specificity.

Main Results:

• Successful radiosynthesis yielded up to 30% of [18F]AlF-NOTA-ADH-1.
• In vitro studies confirmed Cy3-ADH-1 binding to N-cadherin-positive cells.
• In vivo imaging and biodistribution showed higher probe uptake in tumors with greater N-cadherin expression, correlating with immunohistochemistry.
• Blocking experiments validated the N-cadherin-specific uptake of the probe.

Conclusions:

• [18F]AlF-NOTA-ADH-1 was successfully synthesized and demonstrated specific N-cadherin targeting in vitro.
• The probe effectively visualized differential N-cadherin expression in tumors via micro-PET imaging.
• These findings highlight the potential of [18F]AlF-NOTA-ADH-1 as a PET imaging agent for non-invasive assessment of tumor N-cadherin expression.