First-In-Human Study Demonstrating Tumor-Angiogenesis by PET/CT Imaging with 68 Ga-NODAGA-THERANOST,a High-Affinity Peptidomimetic for α v β 3 Integrin Receptor Targeting

Abstract

⁶⁸Ga-NODAGA-THERANOST™ is an α_vβ₃ integrin antagonist and the first radiolabeled peptidomimetic to reach clinical development for targeting integrin receptors. In this first-in-human study, the feasibility of integrin receptor peptidomimetic positron emission tomography/computed tomography (PET/CT) imaging was confirmed in patients with non-small-cell lung cancer and breast cancer.

Methods:

Patients underwent PET/CT imaging with ⁶⁸Ga NODAGA-THERANOST. PET images were analyzed qualitatively and quantitatively and compared to 2-deoxy-2-(¹⁸F) fluoro-d-glucose (¹⁸F-FDG) findings. Images were obtained 60 minutes postinjection of 300–500 MBq of ⁶⁸Ga-NODAGA-THERANOST.

Results:

⁶⁸Ga-NODAGA-THERANOST revealed high tumor-to-background ratios (SUV_max=4.8) and uptake at neoangiogenesis sites. Reconstructed fused images distinguished cancers with high malignancy potential and enabled enhanced bone metastasis detection. ¹⁸F-FDG-positive lung and lymph node metastases did not show uptake, indicating the absence of neovascularization.

Conclusions:

⁶⁸Ga-NODAGA-THERANOST was found to be safe and effective, exhibiting in this study rapid blood clearance, stability, rapid renal excretion, favorable biodistribution and PK/PD, low irradiation burden (μSv/MBq/μg), and convenient radiolabeling. This radioligand might enable theranostics, that is, a combination of diagnostics followed by the appropriate therapeutics, namely antiangiogenic therapy, image-guided presurgical assessment, treatment response evaluation, prediction of pathologic response, neoadjuvant-peptidomimetic-radiochemotherapy, and personalized medicine strategies. Further clinical trials evaluating ⁶⁸Ga-NODAGA-THERANOST are warranted.