Biodistribution and Radiation Dosimetry of ¹²⁴I-DPA-713, a PET Radiotracer for Macrophage-Associated Inflammation

Abstract

Whole-body PET/CT was performed using I-DPA-713, a radioligand for the 18-kDa translocator protein (TSPO), to determine biodistribution and radiation dosimetry. Healthy subjects aged 18-65 y underwent whole-body PET/CT either at 4, 24, and 48 h or at 24, 48, and 72 h after intravenous injection of I-DPA-713. Time-activity curves were generated and used to calculate organ time-integrated activity coefficients for each subject. The resulting time-integrated activity coefficients provided input data for calculation of organ absorbed doses and effective dose for each subject using OLINDA. Subjects were genotyped for the polymorphism rs6971, and plasma protein binding of I-DPA-713 was measured. Three male and 3 female adults with a mean age of 40 ± 19 y were imaged. The mean administered activity and mass were 70.5 ± 5.1 MBq (range, 62.4-78.1 MBq) and 469 ± 34 ng (range, 416-520 ng), respectively. There were no adverse or clinically detectable pharmacologic effects in any of the 6 subjects. No changes in vital signs, laboratory values, or electrocardiograms were observed. I-DPA-713 cleared rapidly (4 h after injection) from the lungs, with hepatic elimination and localization to the gastrointestinal tract. The mean effective dose over the 6 subjects was 0.459 ± 0.127 mSv/MBq, with the liver being the dose-limiting organ (0.924 ± 0.501 mGy/MBq). The percentage of free radiotracer in blood was approximately 30% at 30 and 60 min after injection. I-DPA-713 clears rapidly from the lungs, with predominantly hepatic elimination, and is safe and well tolerated in healthy adults.

Salivary flow rate and radioactivity in saliva, blood and serum of benign and malignant thyroid patients after 131I therapy

“…The retention of iodine was high in serum because the iodine was bound to the plasma proteins other than the proteins involved in the clotting of blood (16,17) . The magnitude of radiation in blood or body was directly proportional to the activity of 131 I administered and also the fractions of radioactive iodine attached to the plasma proteins and other molecules in the tissues (18,19) .…”

Visualizing the dynamics of tuberculosis pathology using molecular imaging

“…A prospective, multicenter, randomized phase IIb clinical trial is under way to evaluate whether baseline stratification of disease burden quantified by 18 F-FDG PET/CT and changes in 18 F-FDG PET/CT parameters at 1 month after treatment initiation can identify pulmonary TB patients who can be cured with 4 months of standard treatment ( 59 ). Although 18 F-FDG PET is currently under investigation, more specific imaging biomarkers, such as 124 I-DPA-713 PET ( 60 , 61 ), and pathogen-specific molecular imaging approaches ( 39 ) could also be used to aid patient stratification, monitor response to treatment, and accelerate the development of novel therapeutics.…”

“…Importantly, disease outcomes in certain forms of TB, such as TB meningitis, may be more strongly associated with changes in intracerebral inflammation than with bacterial killing, as immunoinflammatory damage is a critical pathological process in this disease ( 83 ). Molecular imaging tools could allow noninvasive readouts of neuroinflammation in animal models as well as in human studies ( 60 , 83 ).…”

“…Additionally, 124 I-DPA-713 PET imaging in a rabbit model of TB meningitis showed tracer colocalization with tuberculomas, and postmortem immunohistochemical staining confirmed microglial activation ( 83 ). Biodistribution and dosimetry studies demonstrated that 124 I-DPA-713 PET was safe and well tolerated in humans with low pulmonary background signal ( 60 ). Therefore, 124 I-DPA-713 PET is an example of a molecular imaging approach that could be translated to the clinic to monitor TB-associated microglia/macrophage inflammation.…”

Molecular Imaging: a Novel Tool To Visualize Pathogenesis of Infections In Situ

“…For example, 124 I-DPA-713, a novel tracer for macrophage-associated inflammation, has recently been translated to the clinic. 124 I-DPA-713 PET studies in healthy volunteers demonstrate that 124 I-DPA-713 clears rapidly from the lungs, with predominantly hepatic elimination, and is safe and well tolerated in healthy adults (83). Human studies utilizing 11 C-rifampin PET to study antimicrobial distribution and optimize treatments for TB meningitis (29) and pulmonary TB (49) have also been performed recently.…”