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Objective: The aim of this study was to analyse early and delayed acquisition on copper-64 diacetyl-bisN4-methylthiosemicarbazone (Cu-ATSM) PET/CT in a small cohort of patients by comparing semiquantitative and computer-aided fractal geometry analyses., Patients and Methods: Five cancer patients, including non-small-cell lung cancer and head and neck cancer, were investigated with Cu-ATSM PET/CT. Participants received an intravenous injection of Cu-ATSM according to body size and were imaged 60 min (early) and 16 h (delayed) later on hybrid PET/CT. Reconstructed images were visualized on advanced workstations for the definition of semiquantitative parameters: standardized uptake value (SUV)max, SUVratio-to-muscle, SUVmean, hypoxic volume (HV) and hypoxic burden (HB=HV×SUVmean). DICOM data retrieved from both scans were analysed using an ad-hoc computer program to determine the mean intensity value, SD, relative dispersion, three-dimensional histogram fractal dimension and three-dimensional fractal dimension., Results: All tumour lesions showed increased uptake of Cu-ATSM at early evaluation, with a median SUVratio-to-muscle of 4.42 (range: 1.58-5.62), a median SUVmax of 5.3 (range: 1.9-7.3), a median SUVmean of 2.8 (range: 1.5-3.9), a median HV of 41.6 cm (range: 2.8-453.7) and a median HB of 161.5 cm (range: 4.4-1112.5). All semiquantitative data obtained at 1 h were consistent with the parameters obtained on delayed imaging (P>0.05). A borderline statistically significant difference was found only for SUVmax of the muscle (P=0.045). Fractal geometry analysis on DICOM images showed that all parameters at early imaging showed no statistically significant difference with late acquisition (P>0.05)., Conclusion: Our findings support the consistency of Cu-ATSM PET/CT images obtained at early and delayed acquisition for the assessment of tumour lesions.

Purpose: Cu-ATSM is a very promising PET radiopharmaceutical for tumor imaging of hypoxia. One of the advantages of this compound compared with other hypoxia-avid tracers is the high tumor-to-background signal offered, which guaranties facilitated tumor delineation. This study analyzes optimal semiquantitative and quantitative parameters obtained by Cu-ATSM PET/CT in the same cohort of patients with special focus on their correlation to disease outcome., Patients and Methods: A prospective recruitment of 18 consecutive patients (M:F, 13:5; mean age, 60.7 years) with locally advanced non-small cell lung cancer (n = 7) or head and neck cancer (HNC) was performed. Each participant received 105 to 500 MBq of tracer according to body size and was scanned in a 3-dimensional mode PET/CT 60 minutes after tracer injection. PET images were reconstructed and visualized on a GE Advanced 4.6 workstation for the definition of semiquantitative and quantitative parameters: SUVmax, SUVratio-to-muscle, hypoxic tumor volume (HTV), and hypoxic burden (HB = HTV × SUVmean). These data were subsequently correlated to disease outcome, expressed in terms of progression-free survival calculated on a follow-up period with a median of 14.6 months., Results: All patients showed a moderately to highly increased uptake of Cu-ATSM in tumor lesions, with a mean SUVmax of 5.2 (range, 1.9-8.3) and mean SUVratio of 4.4 (range, 1.6-6.8). In addition, a broad range of HTV and HB was defined as mean values of 99.3 cm (range, 2.5-453.7 cm) and 301 (4.2-1134), respectively. Receiver operating characteristic analysis identified as reference cutoffs with respect to disease outcome with the following values: SUVmax >2.5 (AUC, 0.57; sensitivity, 88.9%; specificity, 50%), SUVratio ≤4.4 (AUC, 0.60; sensitivity, 50; specificity, 83.3%), HTV >160.7 cm (AUC, 0.61; sensitivity, 55.6%; specificity, 75%), and HB >160.7 (AUC, 0.67; sensitivity, 58.3%; specificity, 83.3%). In our cohort, HB showed a statistically significant difference in terms of mean values on the analysis of variance test with respect to disease progression (P = 0.04). On univariate analysis, Cox regression confirmed these findings and showed a significant correlation to progression-free survival for HB (P = 0.05) and HTV (P = 0.02)., Conclusions: In our cohort, the definition of optimal semiquantitative and quantitative parameters on Cu-ATSM PET/CT seems feasible and in line with previously published data. However, when considering the prognostic role with respect to disease outcome, the more robust parameters are represented by HTV and HB.

Aims: Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) is a hypoxia-avid, positron emitter radiotracer. The primary aim of this study is to assess the efficacy of pretherapy Cu-ATSM PET/CT as a prognostic factor of response to therapy. The secondary aims are to investigate if there is a difference between early and late PET/CT scans and if there is a difference between the biologic tumor volume (BTV) in radiotherapy treatment planning calculated between Cu-ATSM and F-FDG, and to assess if Cu-ATSM is a prognostic marker of disease progression., Methods: Eleven patients with head and neck cancer treated with chemoradiotherapy were enrolled prospectively; both Cu-ATSM and F-FDG PET/CT scans before and after treatment were obtained. The Cu-ATSM scans were performed after 1 hour (early) and 16 hours (late)., Results: All patients had stage III or IV squamous cell head and neck cancer; 7 of 11 patients had nodal metastasis, and 22 cancer foci were detected with Cu-ATSM. SUVmax was 16.2 ± 7.9, and there was no significant SUVmax difference between early and late imaging. F-FDG SUVmax before therapy was 15.6 ± 9.4, whereas F-FDG SUVmax after therapy was 1.5 ± 1.2. Sensitivity and specificity values of Cu-ATSM calculated with receiver operating characteristic curves were 100% and 50% considering the SUVmax and 100% and 33% considering the volume, respectively. No difference has been found between the BTV contoured with Cu-ATSM and F-FDG., Conclusions: The Cu-ATSM scans showed high sensitivity but low specificity in predicting neoadjuvant chemoradiotherapy response. No difference was noted between early and late scans. F-FDG and Cu-ATSM provided similar results about delineation of BTV.