PET Imaging of Neurofibromatosis Type 1 with a Fluorine-18 Labeled Tryptophan Radiotracer.

Autor: Yue X; Department of Radiology, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA.; Diagnostic & Research PET/MR Center, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA., Stauff E; Department of Radiology, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA.; Diagnostic & Research PET/MR Center, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA., Boyapati S; Department of Radiology, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA., Langhans SA; Diagnostic & Research PET/MR Center, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA.; Division of Neurology, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA., Xu W; Department of Radiology, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA.; Diagnostic & Research PET/MR Center, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA., Makrogiannis S; Division of Physics, Engineering, Mathematics, and Computer Science, Delaware State University, Dover, DE 19901, USA., Okorie UJ; Division of Physics, Engineering, Mathematics, and Computer Science, Delaware State University, Dover, DE 19901, USA., Okorie AM; Division of Physics, Engineering, Mathematics, and Computer Science, Delaware State University, Dover, DE 19901, USA., Kandula VVR; Department of Radiology, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA., Kecskemethy HH; Department of Radiology, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA.; Diagnostic & Research PET/MR Center, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA., Nikam RM; Department of Radiology, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA.; Diagnostic & Research PET/MR Center, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA., Averill LW; Department of Radiology, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA.; Diagnostic & Research PET/MR Center, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA., Shaffer TH; Nemours Biomedical Research, Nemours Children's Health, Delaware, Wilmington, DE 19803, USA.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2024 May 27; Vol. 17 (6). Date of Electronic Publication: 2024 May 27.
DOI: 10.3390/ph17060685
Abstrakt: Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder. Plexiform neurofibromas (PNFs) are benign tumors commonly formed in patients with NF1. PNFs have a high incidence of developing into malignant peripheral nerve sheath tumors (MPNSTs) with a 5-year survival rate of only 30%. Therefore, the accurate diagnosis and differentiation of MPNSTs from benign PNFs are critical to patient management. We studied a fluorine-18 labeled tryptophan positron emission tomography (PET) radiotracer, 1-(2-[ 18 F]fluoroethyl)-L-tryptophan (L-[ 18 F]FETrp), to detect NF1-associated tumors in an animal model. An ex vivo biodistribution study of L-[ 18 F]FETrp showed a similar tracer distribution and kinetics between the wild-type and triple mutant mice with the highest uptake in the pancreas. Bone uptake was stable. Brain uptake was low during the 90-min uptake period. Static PET imaging at 60 min post-injection showed L-[ 18 F]FETrp had a comparable tumor uptake with [ 1 ⁸F]fluorodeoxyglucose (FDG). However, L-[ 18 F]FETrp showed a significantly higher tumor-to-brain ratio than FDG ( n = 4, p < 0.05). Sixty-minute-long dynamic PET scans using the two radiotracers showed similar kidney, liver, and lung kinetics. A dysregulated tryptophan metabolism in NF1 mice was further confirmed using immunohistostaining. L-[ 18 F]FETrp is warranted to further investigate differentiating malignant NF1 tumors from benign PNFs. The study may reveal the tryptophan-kynurenine pathway as a therapeutic target for treating NF1.
Databáze: MEDLINE
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