Preparation, biological characterization and preliminary human imaging studies of 68Ga-DOTA-IBA

PurposeIn this study, DOTA-IBA was radiolabeled with Ga-68 and we determined the optimum labelling conditions and assessed the biological properties of Ga-68-DOTA-IBA. We investigated the biodistribution of Ga-68-DOTA-IBA in normal animals and undertook PET/CT imaging in humans. Finally, we explored the feasibility Ga-68-DOTA-IBA as a bone imaging agent and demonstrated its potential for the therapeutic release of Lu-177/Ac-225-DOTA-IBA. MethodsThe controlled variables method was used to assess the impact of variables on the radiochemical purity of Ga-68-DOTA-IBA. The biological properties of Ga-68-DOTA-IBA were investigated.Ga-68-DOTA-IBA micro-PET/CT imaging was performed on animals. Volunteers were recruited for Ga-68-DOTA-IBA imaging and data were compared to Tc-99m-MDP imaging studies to calculate the target to non-target ratio (T/NT) of the lesions. ResultsThe prepared Ga-68-DOTA-IBA had a radiochemical purity of >97% and demonstrated good biological properties with a good safety profile in normal mice. PET/CT imaging of the animals showed rapid blood clearance with high contrast between the bone and stroma. Human imaging showed that Ga-68-DOTA-IBA could detect more lesions compared to Tc-99m-MDP and had a higher targeted to untargeted ratio. Conclusions(68)Ga-DOTA-IBA is an osteophilic radiopharmaceutical that can be synthesized using a simple labelling method. Ga-68-DOTA-IBA has high radiochemical purity and is stable in vitro stability. It is rapidly cleared from the blood, has low toxicity and has strong targeting to the bone with long retention times. We also found that it is rapidly cleared in non-target tissues and has high contrast on whole-body bone imaging. Ga-68-DOTA-IBA PET/CT has potential as a novel bone imaging bone modality in patients with metastatic disease.

Automated summary

This study radiolabeled DOTA-IBA with Ga-68, assessed its distribution in animals and imaging in humans, and explored its potential as a bone imaging agent. Ga-68-DOTA-IBA demonstrated high purity, good biological properties, and potential for novel bone imaging modalities.