This study sponsored by GE Healthcare (ClinicalTrials.gov identifier: NCT04564092) was conducted according to International Conference on Harmonisation (ICH) Good Clinical Practice Guideline. It was approved by the Ethics committee of the Ruijin hospital. This single-centre study recruited healthy Chinese volunteers. Eligible subjects were generally healthy and fit Chinese males or females aged 18 to 70 years and with a body mass index (BMI) of 18 to 30 kg/m2. Pregnant or lactating women were ineligible, and women of childbearing potential had to be willing to use effective contraception. Subjects would be excluded if they had a history of motor disturbances; a history of pulmonary, cardiovascular, renal, hepatic, coagulation, or hormonal disorders, including hyperthyroidism; a history of drug, alcohol, or solvent abuse; use of any investigational medicinal product (IMP) within 30 days prior to screening or receipt of any radionuclide injection within a minimum of 5 radioactive half-lives prior to screening; use of any medication except acetaminophen (paracetamol) or oral contraceptive, including traditional Chinese medications, within 2 weeks of the imaging visit; or classification as a radiation worker.

Subjects were to attend 3 visits: screening, imaging, and follow-up. Medical history, physical examination, clinical laboratory tests and urine analysis, and 12-lead Electrocardiogram (ECG) were obtained for screening and safety assessment purposes. To minimise thyroid uptake of radioactive iodine, subjects had to have appropriate thyroid blocking, according to local practice, prior to and after administration of the IMP.

The primary objective of this phase 1 study was to evaluate the safety of a single dose of [123I]ioflupane injection in Chinese healthy volunteers (HVs). The secondary objectives were: (1) To determine the biodistribution, internal radiation dosimetry, and effective dose (ED) of [123I]ioflupane injection after intravenous (IV) administration in Chinese HVs. (2) To compare biodistribution and dosimetry findings in this Chinese group with those previously established in European HVs. (3) To compare the brain SPECT imaging results in this Chinese group with those previously established in European HVs.

GE Healthcare was responsible for the manufacturing, distribution, and reconciliation of the IMP, [123I]ioflupane injection. The IMP was prepared at GE Healthcare BV, Eindhoven, Netherlands.

Whenever possible, images were acquired at prespecified time points. During the imaging visit, each subject received a single IV bolus injection of [123I]ioflupane with a nominal 123I activity of 111 MBq ± 10% and underwent simultaneous whole-body (head to toe) anterior and posterior planar scintigraphy scans on Intevo 16 SPECT/CT system (Siemens, Erlangen, Germany) at 10 min, 1 h, 2 h, 4 h, 5 h, 24 h, and 48 h after administration. Attenuation correction was performed using transmission scans acquired using a flood source filled with a solution of 123I. Brain SPECT imaging was performed at 3 and 6 h after administration. A reference source was imaged alongside the subject. Whole-body planar images were acquired in a 256 × 1024 matrix and a low-energy, high-resolution, parallel-hole collimator. Brain SPECT acquisition was performed using the same collimator, a 128 × 128 matrix, and a total of 32 frames over 180° with 30 s per frame. After acquisition, Butter-worth low-pass filter and Ramp function were used to reconstruct transverse images.

Blood samples were collected before the [123I]ioflupane injection and at 5, 15, 30 min and 1, 2, 3, 4, 5, 24, and 48 h after injection for pharmacokinetic analysis. For each HV, up to 5-mL venous blood samples were taken at each time point to allow measurement of 123I content in whole blood and plasma over time. The maximum amount of blood taken for activity counting was 55 mL for each HV.

Urine excreted from 1 h before administration of [123I]ioflupane injection to 48 h after injection was collected as voided. The time and volume of each void was recorded. From each void, 3 aliquots of urine of a nominal 1 mL volume each were taken and assayed for 123I activity content over 60 s intervals.

The striatal binding ratio (SBR) is a measure of how much [123I]ioflupane binds to DaT in different regions of the brain compared to a reference region where there is no binding. DaTQUANT™ software was used to automatically delineate the volumes of interest (VOIs) in the striatal regions and reference region (occipital lobe), and quantify left and right SBRs from SPECT images acquired at approximately 3 and 6 h post-injection for each subject. The VOIs of sub-regions over the putamen and caudate were also considered using DaTQUANT™ software. To calculate the SBR, DaTQUANT™ uses a formula that involves dividing the average pixel intensity of a VOI by the average pixel intensity of a reference region (REF). The formula is: SBR = (VOI − REF)/REF.

Time-activity curves were then generated from attenuation corrected, conjugate view 123I activity data for each subject and parameterised by mono- or biexponential curve fitting to calculate the normalised cumulative activity in each source region using the OLINDA/EXM Version 1.1 software [9], which was then used along with the Medical Internal Radiation Dosimetry (MIRD) schema to determine the internal radiation dosimetry [10]. The dosimetry was evaluated for the Cristy–Eckerman female and hermaphrodite male phantoms [11].

Tabulations of summary statistics, graphical presentations, and statistical analyses were performed by using SAS® software, Version 9.4. The last observation prior to administration of IMP was used as the baseline value for calculating post-administration changes from baseline. p-values was interpreted as a metric of uncertainty. Confidence intervals, both individual and simultaneous, were at the 95% confidence level. The 2-sample t-test was used to compare the radiation dosimetry data from the Chinese healthy volunteers (HVs) in this study to the HVs in the earlier European study [8]. The difference between the SBR at 3 and 6 h calculated for each subject was tested by Wilcoxon signed-rank test. No sample size calculation was performed. The sample size was chosen to fulfil regulatory requirements.