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Sökning: WFRF:(Sundin Peter) > Annan publikation

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1.
  • Jahan, Mahabuba, et al. (författare)
  • Decreased defluorination by using the novel beta cell imaging agent [18F]FE-DTBZ-d4 in pigs examined by PET
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Fluorine-18 DTBZ-analogues, which selectively targets the vesicular monoamine transporter 2 (VMAT2), have been extensively studied for in vivo quantification of beta cell mass by positron emission tomography (PET).  This study describes a novel deuterated radioligand [18F]FE-(+)-DTBZ-d4, aimed to increase the stability against in vivo defluorination previously observed for [18F]FE-(+)-DTBZ. Methods: [18F]FE-(+)-DTBZ-d4 was synthesized by alkylation of desmethyl -(+)-DTBZ precursor with deuterated  [18F]fluoroethyl bromide ([18F]FCD2CD2Br). Radioligand affinity and specificity to VMAT2 was assessed by an in vitro saturation homogenate binding assay using human endocrine and exocrine pancreatic tissues. In vivo PK/PD was studied in a porcine model by PET/CT. The rate of defluorination was quantified by compartmental modeling and contrasted against defluorination of the non-deuterated analogue. Results: [18F]FE-DTBZ-d4 was produced in good radiochemical yield (3.0-1.7 GBq) in 100 min. Radiochemical purity of the formulated product was > 98% for up to 5h. The in vitro Binding Potential (BP) for VMAT2 in islet tissue was 27.0±8.8. The BP was lower in exocrine tissue (1.7±1.0) in addition to a close to three-fold decrease in specificity. The rate of in vivo defluorination was decreased significantly (kdefluorination= 0.0016±0.0007) compared to the non-deuterated analogue (kdefluorination= 0.012±0.002), resulting in a more than six-fold increase in half-life stability. Conclusion: [18F]FE-(+)-DTBZ-d4 has favorable pharmacokinetic (PK) properties for VMAT2 imaging, in addition to gaining significantly increased stability against defluorination. The in vitro islet BP and specificity was lower compared to a non-deuterated analogue but the islet/exocrine BP ratio was unchanged, potentially allowing for improved target tissue discrimination.
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2.
  • Weber, Manuel, et al. (författare)
  • Changes in Tumor-to-Blood Ratio as a prognostic marker for progression-free survival and overall survival in neuroendocrine tumor patients undergoing PRRT
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background:Historically, patient selection for peptide receptor radionuclide therapy (PRRT) has been performed by virtue of somatostatin-receptor scintigraphy (SRS). In recent years, somatostatin-receptor positron emission tomography (SSTR-PET) has gradually replaced SRS because of its improved diagnostic capacity, creating an unmet need for SSTR-PET-based selection criteria for PRRT. Tumor-to-Blood-ratio (TBR) measurements have shown high correlation with the net influx rate Ki, reflecting the tumor somatostatin-receptor expression, to a higher degree than standardized uptake value (SUV) measurements. TBR may therefore predict treatment response to PRRT. In addition, changes in semiquantitative SSTR-PET parameters have been shown to predate morphological changes, making them a suitable metric for response assessment.  Methods:The institutional database of the Department of Nuclear Medicine (University Hospital Essen) was searched for NET patients undergoing ≥2 PRRT cycles with available baseline and follow-up SSTR-PET. Two blinded independent readers reported the occurrence of new lesions quantified tumor uptake of up to 9 lesions per-patient using SUV, TBR, and tumor-spleen ratio (TSR). The association between baseline TBR and changes in uptake / occurrence of new lesions with progression-free survival (PFS) and overall survival (OS) was tested by use of a Cox regression model and log-rank test. Results: Patients with baseline TBR in the 1st quartile had a shorter PFS (14.4 months) than those in the 3rd (23.7 months; p=0.03) and 4th (24.1 months; p=0.02) quartile. Similarly, these patients had significantly shorter OS (32.5 months) than those with baseline TBR in the 2nd (41.8 months; p=0.03), 3rd (69.2 months; p<0.01), and 4th (42.7 months; p=0.03) quartile. Baseline to follow-up increases in TBR were independently associated with shorter PFS when accounting for prognostic markers, e.g. RECIST response (Hazard Ratio=3.29[95%CI= 1.62-6.68]; p<0.01). This was confirmed with regards to OS (Hazard Ratio=1.94[95%CI= 1.14-3.32]; p=0.02). Changes in TSR and SUVmean were not associated with PFS or OS. Conclusions: Baseline TBR as well as changes in TBR were significantly associated with PFS and OS and may improve patient selection and morphological response assessment. Future trials need to assess the role of TBR for therapy monitoring also during PRRT, and prospectively explore TBR as a predictive marker for patient selection.
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