¹²⁴I-Labeled Specific Antibody Targeting LAG-3 for ImmunoPET.

Area of Science:

• Nuclear medicine
• Molecular imaging
• Immunotherapy

Background:

• Lymphocyte-activation gene 3 (LAG-3) is a key immune checkpoint and a promising therapeutic target.
• Noninvasive methods for assessing LAG-3 expression are currently limited, hindering treatment optimization.

Purpose of the Study:

• To develop and evaluate an antibody-dependent molecular imaging strategy for noninvasive LAG-3 detection using a LAG-3-specific antibody, HuL13.
• To assess the feasibility of using radiolabeled HuL13 for Positron Emission Tomography (PET) imaging of LAG-3 expression.

Main Methods:

• The anti-LAG-3 antibody HuL13 was radiolabeled with Iodine-124 (¹²⁴I).
• Specificity and affinity of ¹²⁴I-HuL13 were confirmed using cell-based assays.
• Micro-PET/CT imaging was performed in mice bearing LAG-3-expressing tumors, followed by immunohistochemistry (IHC) for validation.

Main Results:

• ¹²⁴I-HuL13 showed high radiochemical yield (>95%), purity (>99%), and stability.
• The radiotracer exhibited specific binding to LAG-3-expressing cells with a dissociation constant (Kd) of 23.02 nM.
• In vivo imaging revealed significant accumulation of ¹²⁴I-HuL13 in tumors, with uptake correlating to LAG-3 expression.

Conclusions:

• ¹²⁴I-HuL13 is a stable and effective PET imaging radiotracer for noninvasive LAG-3 detection.
• This molecular imaging approach holds potential for guiding and optimizing LAG-3-targeted immunotherapies in clinical settings.