Purpose

[¹⁸F]F-AraG is a radiolabeled nucleoside analog that shows relative specificity for activated T cells. The aim of this study was to investigate the biodistribution of [¹⁸F]F-AraG in healthy volunteers and assess the preliminary safety and radiation dosimetry.

Methods

Six healthy subjects (three female and three male) between the ages of 24 and 60 participated in the study. Each subject received a bolus venous injection of [¹⁸F]F-AraG (dose range: 244.2-329.3 MBq) prior to four consecutive PET/MR whole-body scans. Blood samples were collected at regular intervals and vital signs monitored before and after tracer administration. Regions of interest were delineated for multiple organs, and the area under the time-activity curves was calculated for each organ and used to derive time-integrated activity coefficient (TIAC). TIACs were input for absorbed dose and effective dose calculations using OLINDA.

Results

PET/MR examination was well tolerated, and no adverse effects to the administration of [¹⁸F]F-AraG were noted by the study participants. The biodistribution was generally reflective of the expression and activity profiles of the enzymes involved in [¹⁸F]F-AraG's cellular accumulation, mitochondrial kinase dGK, and SAMHD1. The highest uptake was observed in the kidneys and liver, while the brain, lung, bone marrow, and muscle showed low tracer uptake. The estimated effective dose for [¹⁸F]F-AraG was 0.0162 mSv/MBq (0.0167 mSv/MBq for females and 0.0157 mSv/MBq for males).

Conclusion

Biodistribution of [¹⁸F]F-AraG in healthy volunteers was consistent with its association with mitochondrial metabolism. PET/MR [¹⁸F]F-AraG imaging was well tolerated, with a radiation dosimetry profile similar to other commonly used [¹⁸F]-labeled tracers. [¹⁸F]F-AraG's connection with mitochondrial biogenesis and favorable biodistribution characteristics make it an attractive tracer with a variety of potential applications.

People living with HIV (HIV+) are roughly twice as likely to smoke cigarettes (Smok+) as the general population. With the advent of effective antiretroviral therapies, it is increasingly important to understand the effects of chronic HIV infection and cigarette smoking on brain function and cognition since HIV+ individuals have heightened neuroinflammation and cognitive deficits even with such therapies. Based on prior studies demonstrating that smoking reduces a marker for neuroinflammation in HIV- individuals, we hypothesized that HIV+/Smok+ individuals would have less neuroinflammation and better cognitive control than HIV+/Smok- individuals. Fifty-nine participants (HIV-/Smok- [n = 16], HIV-/Smok+ [n=14], HIV+/Smok- [n = 18], and HIV+/Smok+ [n = 11]) underwent baseline eligibility tests, positron emission tomography (PET) scanning to determine levels of a marker for neuroinflammation, and assessment of cognitive control with the reverse-translated 5-choice continuous performance test (5C-CPT), with smokers having smoked to satiety prior to testing. For the PET data, a significant effect of smoking status on whole brain (WB) standardized uptake value (SUV) was found between HIV+/Smok+ and HIV+/Smok- participants (due to 18.8% lower WB SUV in the HIV+/Smok+ group). HIV+/Smok- participants exhibited a mean 13.5% higher WB SUV than HIV-/Smok- participants. For the 5C-CPT, HIV+/Smok+ participants performed significantly better than HIV+/Smok- participants (d prime), and HIV+/Smok- participants performed worse than HIV-/Smok- participants. Thus, HIV+/Smok+ individuals demonstrated lower levels of the neuroinflammation marker and better cognitive control than HIV+/Smok- individuals. Given that HIV+ individuals whose HIV is well-controlled can still have chronic neurocognitive complications, study results suggest possible paths for future research into nicotine-related treatments to prevent such complications.