Nuclear medicine and biology最新文献

Introduction: [¹⁸F]fluoro-L-α-methyltyrosine ([¹⁸F]FAMT) has been reported as a positron-emission tomography (PET) probe that has high specificity for L-type amino acid transporter 1 (LAT1), which is overexpressed in various malignant tumors. However, [¹⁸F]FAMT showed rapid washout from the tumor and high retention in the kidney. This study aimed to develop and evaluate a novel LAT1-targeting PET probe, [¹⁸F]FAMT-OMe, and compare its performance with [¹⁸F]FAMT in glioma xenograft mice.

Methods: [¹⁸F]-FAMT-OMe was synthesized via nucleophilic substitution. The uptake of [¹⁸F]FAMT-OMe and [¹⁸F]FAMT was compared in in vitro studies using C6 glioma and U-87MG cells. PET scans were performed on C6 glioma- and U-87MG tumor-bearing mice (n = 20 each) following intravenous administration of either [¹⁸F]FAMT-OMe or [¹⁸F]FAMT. After PET/computed tomography (CT) imaging, the organs were weighed and the radioactivity present was measured using a gamma counter.

Results: In vitro analyses demonstrated higher uptake of [¹⁸F]FAMT-OMe compared with [¹⁸F]FAMT in both C6 and U-87MG cells. PET imaging demonstrated significantly greater tumor retention of [¹⁸F]FAMT-OMe than [¹⁸F]FAMT (SUVmax at 60 min in C6 glioma: 2.13 ± 0.39 vs. 1.09 ± 0.79, P < 0.05). The kidneys and urine showed significantly lower uptake and excretion of [¹⁸F]FAMT-OMe than [¹⁸F]FAMT (kidney uptake: SUVmean 3.75 ± 0.89 vs. 5.55 ± 2.44, P < 0.05 urine excretion: SUVmean 16.50 ± 7.65 vs. 34.38 ± 8.74, P < 0.05), while blood retention of [¹⁸F]FAMT-OMe was significantly increased (SUVmean 1.78 ± 0.85 vs. 1.20 ± 0.82, P < 0.05).

Conclusion: [¹⁸F]FAMT-OMe showed improved tumor retention on PET compared with [¹⁸F]FAMT in the C6 glioma tumor model, suggesting its potential utility for future applications in LAT1-targeted PET.

Introduction: Endometriosis, affecting up to 10% of women, is a chronic estrogen dependent disorder where ectopic endometrial-like tissue causes pelvic pain and infertility. Endometriosis is challenging to diagnose due to symptom overlap and limited imaging accuracy, often requiring surgical visualization. Positron emission tomography (PET) potentially offers a non-invasive, molecular-based approach for highly specific diagnosis and monitoring of endometriosis. Aromatase, typically low in normal endometrial tissue, is elevated in endometriotic lesions, while neutrophils, which are scarce in normal tissue, are increased in these lesions. Fibrosis, resulting from activated platelet-derived growth factor receptor β (PDGFR-β)-expressing myofibroblasts, has been observed in endometriosis lesions. In this study, three PET tracers; [¹¹C]cetrozole ([¹¹C]CET), [¹¹C]GW457427 ([¹¹C]NES), and [⁶⁸Ga]Ga-ATH001, targeting aromatase, neutrophil elastase (NE), and PDGFR-β, respectively, were tested in endometriosis patient biopsies through autoradiography (ARG) combined with histological examinations. A pilot PET/Magnetic resonance imaging (PET/MR) study was performed in endometriosis patients with [¹¹C]NES.

Methods: Ten biopsies from patients with endometriosis were collected. Frozen tissue was sectioned at 20 μm for ARG and 4 μm for immunohistochemistry (IHC). Total binding and non-specific binding, with quantification using ImageJ (fmol/mm³) was determined. Specific binding was calculated as total minus non-specific binding and expressed as a percentage. Sections were stained with Hematoxylin and Eosin (H/E) and Cytokeratin7 (CK7) for morphology, Sirius Red (SIR) for fibrosis, antibodies against PDGFR-β and NE. Neutrophil extracellular traps (NETs) were identified by combined staining for NE and Histone H3. Three endometriosis patients were scanned with [¹¹C]NES by PET/MR.

Results: All three tracers showed high in vitro binding to endometriotic tissue in ARG. [¹¹C]NES and [⁶⁸Ga]Ga-ATH001 had high degree of specific binding to elastase and PDGFR-β, respectively, whereas no specific binding could be shown for [¹¹C]CET. ARG results were validated by IHC: CK7 confirmed epithelial lesions, NE and Histone H3 verified neutrophils and NETs, and PDGFR-β/SIR indicated fibrosis. However, in vivo, no [¹¹C]NES uptake was detected on the PET/MR scans of the three endometriosis patients.

Conclusion: In ARG on endometriotic tissue samples, [⁶⁸Ga]Ga-ATH001 and [¹¹C]NES showed specific binding to their respective targets. However, tracer delivery potentially forms a challenge in visualizing fibrotic endometriosis lesions in vivo, as seen by [¹¹C]NES PET/MR in patients.