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

• Published in: Annals of nuclear medicine 2019-06, Vol.33 (6), p.404-413
• Main Authors: Khawar, Ambreen, Eppard, Elisabeth, Roesch, Frank, Ahmadzadehfar, Hojjat, Kürpig, Stefan, Meisenheimer, Michael, Gaertner, Florian. C., Essler, Markus, Bundschuh, Ralph. A.
• Format: Article
• Language: English
• Subjects: Biocompatibility; Biomedical materials; Bisphosphonates; Bladder; Blood; Bone diseases; Bone imaging; Bone marrow; Computed tomography; Computer programs; Diagnosis; Diagnostic systems; Diuresis; Dosimeters; Dosimetry; Excretion; Fluorine isotopes; Gallium; Image reconstruction; Imaging; Kidneys; Liver; Lutetium isotopes; Medical diagnosis; Medical imaging; Medicine; Medicine & Public Health; Metastases; Nuclear Medicine; Organs; Original Article; Qualitative analysis; Quantitative analysis; Radiology; Salivary gland; Salivary glands; Skeleton; Software; Spleen; Tomography; Urinary bladder; Urine; Zoledronic acid
• ISSN: 0914-7187; 1864-6433
• DOI: 10.1007/s12149-019-01348-7

Objective Pre-clinical studies with gallium-68 zoledronate ([ 68 Ga]Ga-DOTA ZOL ) have proposed it to be a potent bisphosphonate for PET/CT diagnosis of bone diseases and diagnostic counterpart to [ 177 Lu]Lu-DOTA ZOL and [ 225 Ac]Ac-DOTA ZOL . This study aims to be the first human biodistribution and dosimetric analysis of [ 68 Ga]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 [ 68 Ga]Ga-DOTA ZOL i.v. Biodistribution of [ 68 Ga]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 [ 68 Ga]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 [ 68 Ga]Ga-DOTA ZOL was comparable to [ 18 F]NaF, [ 99m Tc]Tc-MDP and [ 68 Ga]Ga-PSMA-617. With proper hydration and diuresis to reduce urinary bladder and kidney absorbed doses, it has clear advantages over [ 18 F]NaF owing to its onsite, low-cost production and theranostic potential of personalized dosimetry for treatment with [ 177 Lu]Lu-DOTA ZOL and [ 225 Ac]Ac-DOTA ZOL .