RT Journal Article
SR Electronic
T1 Development of Fluorinated NP-59: A Revival of Cholesterol Use Imaging with PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1949
OP 1955
DO 10.2967/jnumed.122.263864
VO 63
IS 12
A1 Allen F. Brooks
A1 Wade P. Winton
A1 Jenelle Stauff
A1 Janna Arteaga
A1 Bradford Henderson
A1 Jeremy Niedbala
A1 Peter J.H. Scott
A1 Benjamin L. Viglianti
YR 2022
UL http://jnm.snmjournals.org/content/63/12/1949.abstract
AB Imaging of cholesterol use is possible with the 131I scintiscanning/SPECT agent NP-59. This agent provided a noninvasive measure of adrenal function and steroid synthesis. However, iodine isotopes resulted in poor resolution, manufacturing challenges, and high radiation dosimetry to patients that have limited their use and clinical impact. A 18F analog would address these shortcomings while retaining the ability to image cholesterol use. The goal of this study was to prepare and evaluate a 18F analog of NP-59 to serve as a PET imaging agent for functional imaging of the adrenal glands based on cholesterol use. Previous attempts to prepare such an analog of NP-59 have proven elusive. Preclinical and clinical evaluation could be performed once the new fluorine analog of NP-59 production was established. Methods: The recent development of a new reagent for fluorination along with an improved route to the NP-59 precursor allowed for the preparation of a fluorine analog of NP-59, FNP-59. The radiochemistry for the 18F-radiolabeled 18F-FNP-59 is described, and rodent radiation dosimetry studies and in vivo imaging in New Zealand rabbits was performed. After in vivo toxicity studies, an investigational new drug approval was obtained, and the first-in-humans images with dosimetry using the agent were acquired. Results: In vivo toxicity studies demonstrated that FNP-59 is safe for use at the intended dose. Biodistribution studies with 18F-FNP-59 demonstrated a pharmacokinetic profile similar to that of NP-59 but with decreased radiation exposure. In vivo animal images demonstrated expected uptake in tissues that use cholesterol: gallbladder, liver, and adrenal glands. In this first-in-humans study, subjects had no adverse events and images demonstrated accumulation in target tissues (liver and adrenal glands). Manipulation of uptake was also demonstrated with patients who received cosyntropin, resulting in improved uptake. Conclusion: 18F-FNP-59 provided higher resolution images, with lower radiation dose to the subjects. It has the potential to provide a noninvasive test for patients with adrenocortical diseases.