Details

Autor(en) / Beteiligte

• Bouleau, Alizée
• Nozach, Hervé
• Dubois, Steven
• Kereselidze, Dimitri
• Chevaleyre, Céline
• Wang, Cheng-I
• Evans, Michael J
• Lebon, Vincent
• Maillère, Bernard
• Truillet, Charles

Titel

Optimizing Immuno-PET Imaging of Tumor PD-L1 Expression: Pharmacokinetic, Biodistribution, and Dosimetric Comparisons of 89 Zr-Labeled Anti-PD-L1 Antibody Formats

Ist Teil von

• Journal of Nuclear Medicine, 2022-08, Vol.63 (8), p.1259-1265

Ort / Verlag

United States: Society of Nuclear Medicine

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• PET imaging of programmed cell death ligand 1 (PD-L1) may help to noninvasively predict and monitor responses to anti-programmed cell death 1/anti-PD-L1 immunotherapies. In this study, we compared the imaging characteristics of 3 radioligands derived from the anti-PD-L1 IgG1 complement 4 (C4). In addition to the IgG C4, we produced a fragment antigen-binding (Fab) C4, as well as a double-mutant IgG C4 (H310A/H435Q) with minimal affinity for the murine neonatal Fc receptor. The pharmacokinetics, biodistribution, and dosimetry of the 3 Zr-labeled C4 ligands were compared by longitudinal PET/CT imaging in nude mice bearing subcutaneous human non-small cell lung cancer xenografts with positive (H1975 model) or negative (A549 model) endogenous PD-L1 expression. The C4 radioligands substantially accumulated in PD-L1-positive tumors but not in PD-L1-negative tumors or in blocked PD-L1-positive tumors, confirming their PD-L1-specific tumor targeting. Zr-Fab C4 and Zr-IgG C4 (H310A/H435Q) were rapidly eliminated compared with Zr-IgG C4. Consequently, maximal tumor-to-muscle ratios were obtained earlier, at 4 h after injection for Zr-Fab C4 (ratio, ∼6) and 24 h after injection for Zr-IgG C4 (H310A/H435Q) (ratio, ∼9), versus 48 h after injection for Zr-IgG C4 (ratio, ∼8). Background activity in nontumor tissues was low, except for high kidney retention of Zr-Fab C4 and persistent liver accumulation of Zr-IgG C4 (H310A/H435Q) compared with Zr-IgG C4. Dosimetry estimates suggested that the C4 radioligands would yield organ-absorbed doses tolerable for repeated clinical PET imaging studies. This study highlights the potential of designing radioligands with shorter pharmacokinetics for PD-L1 immuno-PET imaging in a preclinical model and encourages further clinical translation of such radioligands.