Preliminary results of biodistribution and dosimetric analysis of [68Ga]Ga-DOTAZOL: a new zoledronate-based bisphosphonate for PET/CT diagnosis of bone diseases

Abstract

Objective: Pre-clinical studies with gallium-68 zoledronate ([⁶⁸Ga]Ga-DOTA^ZOL) have proposed it to be a potent bisphosphonate for PET/CT diagnosis of bone diseases and diagnostic counterpart to [¹⁷⁷Lu]Lu-DOTA^ZOL and [²²⁵Ac]Ac-DOTA^ZOL. This study aims to be the first human biodistribution and dosimetric analysis of [⁶⁸Ga]Ga-DOTA^ZOL.

Methods: Five metastatic skeletal disease patients (mean age: 72 years, M: F; 4:1) were injected with 150-190 MBq (4.05-5.14 mCi) of [⁶⁸Ga]Ga-DOTA^ZOL i.v. Biodistribution of [⁶⁸Ga]Ga-DOTA^ZOL was studied with PET/CT initial dynamic imaging for 30 min; list mode over abdomen (reconstructed as six images of 300 s) followed by static (skull to mid-thigh) imaging at 45 min and 2.5 h with Siemens Biograph 2 PET/CT camera. Also, blood samples (8 time points) and urine samples (2 time points) were collected over a period of 2.5 h. Total activity (MBq) in source organs was determined using interview fusion software (MEDISO Medical Imaging Systems, Budapest, Hungary). A blood-based method for bone marrow self-dose determination and a trapezoidal method for urinary bladder contents residence time calculation were used. OLINDA/EXM version 2.0 software (Hermes Medical Solutions, Stockholm, Sweden) was used to generate residence times for source organs, organ absorbed doses and effective doses.

Results: High uptake in skeleton as target organ, kidneys and urinary bladder as organs of excretion and faint uptake in liver, spleen and salivary glands were seen. Qualitative and quantitative analysis supported fast blood clearance, high bone to soft tissue and lesion to normal bone uptake with [⁶⁸Ga]Ga-DOTA^ZOL. Urinary bladder with the highest absorbed dose of 0.368 mSv/MBq presented the critical organ, followed by osteogenic cells, kidneys and red marrow receiving doses of 0.040, 0.031 and 0.027 mSv/MBq, respectively. The mean effective dose was found to be 0.0174 mSv/MBq which results in an effective dose of 2.61 mSv from 150 MBq.

Conclusions: Biodistribution of [⁶⁸Ga]Ga-DOTA^ZOL was comparable to [¹⁸F]NaF, [^99mTc]Tc-MDP and [⁶⁸Ga]Ga-PSMA-617. With proper hydration and diuresis to reduce urinary bladder and kidney absorbed doses, it has clear advantages over [¹⁸F]NaF owing to its onsite, low-cost production and theranostic potential of personalized dosimetry for treatment with [¹⁷⁷Lu]Lu-DOTA^ZOL and [²²⁵Ac]Ac-DOTA^ZOL.

Keywords: 68Ga]Ga-DOTAZOL; Biodistribution; Bronchial carcinoma; Metastatic skeletal disease; Theranostic radionuclides.