For the successful clinical advancement of exosome therapeutics, the biodistribution and pharmacokinetic profile of exogenous exosomes in various animal models must be determined. Compared with fluorescence or bioluminescence imaging, radionuclide imaging confers multiple advantages for the in vivo tracking of biomolecular therapeutics because of its excellent sensitivity for deep tissue imaging and potential for quantitative measurement. Herein, we assessed the quantitative biodistribution and pharmacokinetics of good manufacturing practice-grade therapeutic exosomes labeled with zirconium-89 (⁸⁹Zr) after systemic intravenous administration in mice and rats. Quantitative biodistribution analysis by positron emission tomography/computed tomography and gamma counting in mice and rats revealed that the total ⁸⁹Zr signals in the organs were lower in rats than in mice, suggesting a higher excretion rate of exosomes in rats. A prolonged ⁸⁹Zr signal for up to 7 days in most organs indicated that substantial amounts of exosomes were taken up by the parenchymal cells in those organs, highlighting the therapeutic potential of exosomes for the intracellular delivery of therapeutics. Exosomes were mainly distributed in the liver and to a lesser extent in the spleen, while a moderately distributed in the kidney, lung, stomach, intestine, urinary bladder, brain, and heart. Exosomes were rapidly cleared from the blood circulation, with a rate greater than that of free ⁸⁹Zr, indicating that exosomes might be rapidly taken up by cells and tissues.

We performed in vivo PET imaging with 3-[¹⁸F]F-CP118,954 (1) for acetylcholinesterase (AChE) and [¹⁸F]fluoromethyl-PBR28-d₂ (2) for translocator protein 18-kDa (TSPO) to investigate the inflammatory brain response after stroke. Imaging studies were performed in the middle cerebral artery occlusion (MCAO) Sprague-Dawley rat model for a period of three weeks. The percentage injected dose per tissue weight (%ID/g) of striatum of 1, and cortex of 2 were obtained, respectively. To trace the sequential inflammatory responses, AChE imaging of 1 was done on post-MCAO day 2, after giving cold PK-11195 for 1 day, and TSPO imaging of 2 was carried out on post-MCAO day 11, after giving donepezil for 10 days. AChE activity in the MCAO-lesioned side were significantly higher than that of the contralateral side on day one, and TSPO activity was highest on day 11. TSPO inhibitor, PK-11195 did not affect AChE activity on day two, while AChE inhibitor, donepezil significantly lowered TSPO binding on day 12. Our study demonstrates that AChE level is elevated in the early course of brain ischemia as a trigger for the inflammatory response, and TSPO level is elevated persistently throughout the post-ischemic injury in the brain. Also, the AChE inhibitor may be able to inhibit or delay neurotoxic inflammatory responses and serve as a beneficial treatment option.

Background: Integrin α _v β ₃ is a molecular marker for the estimation of tumor angiogenesis. ^99m Tc-IDA-D-[c(RGDfK)] ₂ (also known as BIK-505) is a recently developed radiotracer for single-photon emission computed tomography, with good affinity for integrin α _v β ₃ . In this study, the authors investigated the whole-body distribution and internal radiation dosimetry of ^99m Tc-IDA-D-[c(RGDfK)] ₂ in elderly human participants. Materials and Methods: Six healthy volunteers underwent whole-body simultaneous anterior and posterior scans, preceded by transmission scans using cobalt-57 flood source, with a dual head gamma camera system, at 0, 1, 2, 4, 8, and 24 h postinjection of ^99m Tc-IDA-D-[c(RGDfK)] ₂ (injected radioactivity [mean ± SD] = 388.7 ± 29.3 MBq). Anterior and posterior images were geometrically averaged and attenuation corrected to delineate the regions of interest in the liver, gallbladder, kidneys, urinary bladder, spleen, brain, and large intestine. Radiation dose for each organ and the effective doses (EDs) were estimated using OLINDA/EXM 1.1 software. Results: High radiation doses of renal and biliary excretion tracks such as the urinary bladder wall, upper large intestine, kidneys, liver, and gallbladder wall (19.15 ± 6.84, 19.28 ± 4.78, 15.67 ± 0.90, 9.13 ± 1.71, and 9.09 ± 2.03 μGy/MBq, respectively) were observed. The ED and effective dose equivalent were 5.08 ± 0.53 and 7.11 ± 0.58 μSv/MBq, respectively. Conclusions: Dosimetry results were comparable to other radiolabeled peptides and were considered safe and efficient for clinical usage.

[⁶⁸Ga]PSMA-11 is a prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for diagnostic PET imaging. Its application can be extended to targeted radionuclide therapy (TRT). In this study, we characterize the biodistribution and pharmacokinetics of [⁶⁸Ga]PSMA-11 in PSMA-positive and negative (22Rv1 and PC3, respectively) tumor-bearing mice and subsequently estimated its internal radiation dosimetry via voxel-level dosimetry using a dedicated Monte Carlo simulation to evaluate the absorbed dose in the tumor directly. Consequently, this approach overcomes the drawbacks of the conventional organ-level (or phantom-based) method. The kidneys and urinary bladder both showed substantial accumulation of [⁶⁸Ga]PSMA-11 without exhibiting a washout phase during the study. For the tumor, a peak concentration of 4.5 ± 0.7 %ID/g occurred 90 min after [⁶⁸Ga]PSMA-11 injection. The voxel- and organ-level methods both determined that the highest absorbed dose occurred in the kidneys (0.209 ± 0.005 Gy/MBq and 0.492 ± 0.059 Gy/MBq, respectively). Using voxel-level dosimetry, the absorbed dose in the tumor was estimated as 0.024 ± 0.003 Gy/MBq. The biodistribution and pharmacokinetics of [⁶⁸Ga]PSMA-11 in various organs of subcutaneous prostate cancer xenograft model mice were consistent with reported data for prostate cancer patients. Therefore, our data supports the use of voxel-level dosimetry in TRT to deliver personalized dosimetry considering patient-specific heterogeneous tissue compositions and activity distributions.

So Hyeon Park, Yoo Sung Song, Byung Seok Moon, Byung Chul Lee, Hyun Soo Park and Sang Eun Kim. Exp Neurobiol. 2019;28:602-11. https://doi.org/10.5607/en.2019.28.5.602