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

Abstract

PurposeIn this study, DOTA-IBA was radiolabeled with 68Ga and we determined the optimum labelling conditions and assessed the biological properties of 68Ga-DOTA-IBA. We investigated the biodistribution of 68Ga-DOTA-IBA in normal animals and undertook PET/CT imaging in humans. Finally, we explored the feasibility 68Ga-DOTA-IBA as a bone imaging agent and demonstrated its potential for the therapeutic release of 177Lu/225Ac-DOTA-IBA.MethodsThe controlled variables method was used to assess the impact of variables on the radiochemical purity of 68Ga-DOTA-IBA. The biological properties of 68Ga-DOTA-IBA were investigated.68Ga-DOTA-IBA micro-PET/CT imaging was performed on animals. Volunteers were recruited for 68Ga-DOTA-IBA imaging and data were compared to 99mTc-MDP imaging studies to calculate the target to non-target ratio (T/NT) of the lesions.ResultsThe prepared 68Ga-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 68Ga-DOTA-IBA could detect more lesions compared to 99mTc-MDP and had a higher targeted to untargeted ratio.Conclusions68Ga-DOTA-IBA is an osteophilic radiopharmaceutical that can be synthesized using a simple labelling method. 68Ga-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. 68Ga-DOTA-IBA PET/CT has potential as a novel bone imaging bone modality in patients with metastatic disease.

Safety and Efficacy of 68Ga- or 177Lu-Labeled DOTA-IBA as a Novel Theranostic Radiopharmaceutical for Bone Metastases

“…Patients had received surgery, radiotherapy, chemotherapy, endocrinotherapy, immunotherapy, targeted therapy, or diphosphonate as previous treatments and were on palliative treatment with no other treatment options available or unwilling to accept other treatments except for 177 Lu-DOTA-IBA at the time of inclusion. Adequate bone marrow function, including a hemoglobin level of more than 60 g/L, total leukocyte counts greater than 2.5 × 10 9 /L, and platelet counts greater than 60 × 10 9 /L, was required for eligibility. Estimated life expectancy had to be at least 3 months.…”

A New Radiopharmaceutical 225Ac-DOTA-IBA in the Treatment of a Case of Bone Metastases

“…225 Ac-based prostate-specific membrane antigen–targeted therapy and peptide receptor radionuclide therapy are emerging as the promising new modalities for the treatment of metastatic castration-resistant prostate cancer 9,10 and neuroendocrine tumor 11–13 . DOTA-IBA is new a precursor targeting bone metastasis, which can be used for radionuclide labeling with 68 Ga, 177 Lu, and 225 Ac for the diagnosis or treatment of bone metastasis 1,2 . This case showed 225 Ac-DOTA-IBA has a satisfactory therapeutic efficacy in the treatment of bone metastasis.…”

“…This study has been approved by the ethics committee of The Affiliated Hospital of Southwest Medical University (KY2022114). Before treatment, she underwent 68 Ga-DOTA-IBA (a new tracer for evaluating bone metastasis 1,2 ) PET/CT imaging. Maximum intensity projection ( A ), axial PET ( B – D) , fused ( E – G ), and CT images ( H – J ) showed multiple bone destruction with increased tracer uptake.…”

177Lu-DOTA-IBA Therapy in Prostate Cancer With Bone Metastases

“…Preclinical studies of 68 Ga/ 177 Lu-DOTA-IBA showed high hydroxyapatite binding, good target-to-background ratio, and rapid renal clearance, providing a set of potential diagnostic and therapeutic integrative radiopharmaceuticals. 1,3 Our case showed 177 Lu-DOTA-IBA is a promising therapeutic option for the treatment of bone metastasis in prostate cancer, but more studies and experiments are needed.…”

“…ChiCTR2200064487). Before treatment, he underwent PET/CT imaging with 68 Ga-DOTA-IBA (a new tracer for evaluating bone metastasis [1][2][3] ). Maximum intensity projection (A) image showed multiple elevated tracer uptake in the whole body bones.…”