A receptor-targeted fluorescent radiopharmaceutical for multireporter sentinel lymph node imaging

Area of Science:

• Radiopharmaceutical development
• Molecular imaging
• Bioconjugation chemistry

Background:

• Sentinel lymph node (SLN) mapping is crucial for cancer staging.
• Current SLN mapping techniques have limitations in sensitivity and specificity.
• Multimodal probes offer potential for improved diagnostic accuracy.

Purpose of the Study:

• To evaluate the imaging and receptor-binding characteristics of a novel multireporter probe for SLN mapping.
• To assess the probe's efficacy using both nuclear and fluorescence detection modalities.
• To determine the optimal dosage for receptor-mediated imaging.

Main Methods:

• Synthesis of a multireporter probe by conjugating cyanine 7 (Cy7) to tilmanocept.
• In vitro binding assays using receptor-bearing macrophages to determine affinity.
• In vivo optical sentinel lymph node imaging in mice at different molar doses of the probe.
• Quantification of radioactivity and fluorescence in lymph nodes to assess uptake and extraction.

Main Results:

• The probe exhibited subnanomolar affinity in vitro (Kd = 0.25 nmol/L).
• Fluorescence imaging demonstrated high detection sensitivity.
• All evaluated imaging metrics were significantly higher in the low-dose group, confirming receptor-mediated uptake.
• The probe successfully mapped sentinel lymph nodes in vivo.

Conclusions:

• The 99mTc-labeled Cy7 tilmanocept probe possesses robust in vitro and in vivo receptor-binding properties.
• This multireporter probe facilitates successful receptor-targeted sentinel lymph node mapping.
• The probe is effective for combined nuclear and optical imaging applications.