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Purpose: This study aimed to explore the value of [68Ga]Ga-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in the initial staging of patients with newly diagnosed nasopharyngeal carcinoma (NPC), compared with 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) PET/CT. Materials and Methods: Forty-seven treatment-naïve patients with newly diagnosed NPC underwent magnetic resonance imaging (MRI), [68Ga]Ga-DOTA-FAPI-04 PET/CT and [18F]F-FDG PET/CT within 1 week. The diagnostic efficiency of all imaging modalities for evaluating primary tumour extension was compared from the two aspects of soft tissue and bony structure involvement. The accuracy of two PET/CT methods for diagnosing cervical lymph node (CLN) metastases was compared, and MRI served as the standard reference. T and N stages were assessed by MRI, [68Ga]Ga-FAPI PET/CT and [18F]F-FDG PET/CT. Immunohistochemical (IHC) staining for FAP was conducted in 22 of the patients. Results: [68Ga]Ga-FAPI PET/CT outperformed [18F]F-FDG PET/CT in the assessment of primary tumour invasion in the cavernous sinus (10 vs. 1, p < 0.001) and bony structures (207 vs. 177, p < 0.001). Compared with MRI, [68Ga]Ga-FAPI PET/CT upgraded and underestimated T stage in 13 and 2 patients, while [18F]F-FDG PET/CT upgraded and underestimated T stage in 5 and 13 patients. However, [68Ga]Ga-FAPI PET/CT was inferior to [18F]F-FDG PET/CT in diagnosing positive CLNs based on the analyses of patients, neck sides, neck levels and individual nodes. [68Ga]Ga-FAPI PET/CT changed therapeutic schedules in 8 patients because of stage group changes. The presence of FAP with high quantity and intensity in cancer-associated fibroblasts (CAFs) was confirmed in all tumour specimens. Conclusion: [68Ga]Ga-FAPI PET/CT outperformed [18F]F-FDG PET/CT in detecting the cavernous sinus and bony structure involvement of primary NPC tumours, suggesting its value in improving T staging and therapeutic regimen selection. However, the performance of [68Ga]Ga-FAPI PET/CT is less promising for N staging because it detected fewer positive CLNs than [18F]F-FDG PET/CT. [ABSTRACT FROM AUTHOR]

By enabling the non-invasive monitoring and quantification of biomolecular processes, molecular imaging has dramatically improved our understanding of disease. In recent years, non-invasive access to the molecular drivers of health versus disease has emboldened the goal of precision health, which draws on concepts borrowed from process monitoring in engineering, wherein hundreds of sensors can be employed to develop a model which can be used to preventatively detect and diagnose problems. In translating this monitoring regime from inanimate machines to human beings, precision health posits that continual and on-the-spot monitoring are the next frontiers in molecular medicine. Early biomarker detection and clinical intervention improves individual outcomes and reduces the societal cost of treating chronic and late-stage diseases. However, in current clinical settings, methods of disease diagnoses and monitoring are typically intermittent, based on imprecise risk factors, or self-administered, making optimization of individual patient outcomes an ongoing challenge. Low-cost molecular monitoring devices capable of on-the-spot biomarker analysis at high frequencies, and even continuously, could alter this paradigm of therapy and disease prevention. When these devices are coupled with molecular imaging, they could work together to enable a complete picture of pathogenesis. To meet this need, an active area of research is the development of sensors capable of point-of-care diagnostic monitoring with an emphasis on clinical utility. However, a myriad of challenges must be met, foremost, an integration of the highly specialized molecular tools developed to understand and monitor the molecular causes of disease with clinically accessible techniques. Functioning on the principle of probe-analyte interactions yielding a transducible signal, probes enabling sensing and imaging significantly overlap in design considerations and targeting moieties, however differing in signal interpretation and readout. Integrating molecular sensors with molecular imaging can provide improved data on the personal biomarkers governing disease progression, furthering our understanding of pathogenesis, and providing a positive feedback loop toward identifying additional biomarkers and therapeutics. Coupling molecular imaging with molecular monitoring devices into the clinical paradigm is a key step toward achieving precision health. [ABSTRACT FROM AUTHOR]

Purpose: To identify optimal machine learning methods for radiomics-based differentiation of local recurrence versus inflammation from post-treatment nasopharyngeal positron emission tomography/X-ray computed tomography (PET/CT) images.Procedures: Seventy-six nasopharyngeal carcinoma (NPC) patients were enrolled (41/35 local recurrence/inflammation as confirmed by pathology). Four hundred eighty-seven radiomics features were extracted from PET images for each patient. The diagnostic performance was investigated for 42 cross-combinations derived from 6 feature selection methods and 7 classifiers. Of the original cohort, 70 % was applied for feature selection and classifier development, and the remaining 30 % used as an independent validation set. The diagnostic performance was evaluated using area under the ROC curve (AUC), test error, sensitivity, and specificity. Furthermore, the performance of the radiomics signatures against routine features was statistically compared using DeLong's method.Results: The cross-combination fisher score (FSCR) + k-nearest neighborhood (KNN), FSCR + support vector machines with radial basis function kernel (RBF-SVM), FSCR + random forest (RF), and minimum redundancy maximum relevance (MRMR) + RBF-SVM outperformed others in terms of accuracy (AUC 0.883, 0.867, 0.892, 0.883; sensitivity 0.833, 0.864, 0.831, 0.750; specificity 1, 1, 0.873, 1) and reliability (test error 0.091, 0.136, 0.150, 0.136). Compared with conventional metrics, the radiomics signatures showed higher AUC values (0.867-0.892 vs. 0.817), though the differences were not statistically significant (p = 0.462-0.560).Conclusion: This study identified the most accurate and reliable machine learning methods, which could enhance the application of radiomics methods in the precision of diagnosis of NPC. [ABSTRACT FROM AUTHOR]

Purpose: The objective of the present study is to determine whether uptake of [(18)F]fluoromethylcholine ([(18)F]FCH) in comparison with 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) accurately reflects chemotherapy efficacy at the tumor cell level in prostate cancer (PC).Procedures: The effects of docetaxel and cabazitaxel on viable tumor cell number were explored in four PC cell lines. Cellular uptake of [(18)F]FDG and [(18)F]FCH was compared with the effects measured using sulforhodamine B (SRB) assay, cell counting and colony formation assay (CFA), as proximators of viable tumor cell number. Agreement between uptake and cell numbers was assessed by Bland-Altman plots.Results: [(18)F]FCH uptake in all PC cell lines significantly correlated to the cell numbers surviving the respective drug concentrations. Bland-Altman analysis showed that [(18)F]FDG uptake resulted in signal overestimation and higher variability after chemotherapy.Conclusions: [(18)F]FCH uptake correlates well with viable tumor cell numbers remaining after docetaxel and cabazitaxel exposure. Radiolabeled choline is a potential response monitoring biomarker after chemotherapy for PC. [ABSTRACT FROM AUTHOR]

Purpose: (2RS,4S)-2-[(18)F]Fluoro-4-phosphonomethyl-pentanedioic acid (BAY1075553) shows increased uptake in prostate cancer cells. We compared the diagnostic potential of positron emission tomography (PET)-X-ray computed tomography (CT) imaging using BAY1075553 versus [(18)F]f luorocholine (FCH) PET-CT.Procedures: Twelve prostate cancer patients (nine staging, three re-staging) were included. The mean prostate-specific antigen in the primary staging and re-staging groups was 21.5 ± 12 and 73.6 ± 33 ng/ml, respectively. Gleason score ranged from 5-9. In nine patients imaged for pre-operative staging, the median Gleason score was 8 (range, 7-9). PET acquisition started with dynamic PET images in the pelvic region followed by static whole-body acquisition. The patients were monitored for 5-8 days afterward for adverse events.Results: There were no relevant changes in laboratory values or physical examination. Urinary bladder wall received the largest dose equivalent 0.12 mSv/MBq. The whole-body mean effective dose was 0.015 mSv/MBq. There was a significant correlation between detected prostatic lesions by the two imaging modalities (Kappa = 0.356, P < 0.001) and no significant difference in sensitivity (P = 0.16) and specificity (P = 0.41). The sensitivity and specificity of PET imaging using BAY1075553 for lymph node (LN) staging was 42.9 % and 100 %, while it was 81.2 % and 50 % using FCH. The two modalities were closely correlated regarding detection of LNs and bone metastases, although BAY1075553 failed to detect a bone marrow metastasis. Degenerative bone lesions often displayed intense uptake of BAY1075553.Conclusions: BAY1075553 PET-CT produced no adverse effects, was well tolerated, and detected primary and metastatic prostate cancer. FCH PET-CT results were superior, however, with respect to detecting LN and bone marrow metastases. [ABSTRACT FROM AUTHOR]

Purpose: (2RS,4S)-2-[F]Fluoro-4-phosphonomethyl-pentanedioic acid (BAY1075553) shows increased uptake in prostate cancer cells. We compared the diagnostic potential of positron emission tomography (PET)-X-ray computed tomography (CT) imaging using BAY1075553 versus [F]f luorocholine (FCH) PET-CT. Procedures: Twelve prostate cancer patients (nine staging, three re-staging) were included. The mean prostate-specific antigen in the primary staging and re-staging groups was 21.5 ± 12 and 73.6 ± 33 ng/ml, respectively. Gleason score ranged from 5-9. In nine patients imaged for pre-operative staging, the median Gleason score was 8 (range, 7-9). PET acquisition started with dynamic PET images in the pelvic region followed by static whole-body acquisition. The patients were monitored for 5-8 days afterward for adverse events. Results: There were no relevant changes in laboratory values or physical examination. Urinary bladder wall received the largest dose equivalent 0.12 mSv/MBq. The whole-body mean effective dose was 0.015 mSv/MBq. There was a significant correlation between detected prostatic lesions by the two imaging modalities (Kappa = 0.356, P < 0.001) and no significant difference in sensitivity ( P = 0.16) and specificity ( P = 0.41). The sensitivity and specificity of PET imaging using BAY1075553 for lymph node (LN) staging was 42.9 % and 100 %, while it was 81.2 % and 50 % using FCH. The two modalities were closely correlated regarding detection of LNs and bone metastases, although BAY1075553 failed to detect a bone marrow metastasis. Degenerative bone lesions often displayed intense uptake of BAY1075553. Conclusions: BAY1075553 PET-CT produced no adverse effects, was well tolerated, and detected primary and metastatic prostate cancer. FCH PET-CT results were superior, however, with respect to detecting LN and bone marrow metastases. [ABSTRACT FROM AUTHOR]

Purpose: The objective of the present study is to determine whether uptake of [F]fluoromethylcholine ([F]FCH) in comparison with 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) accurately reflects chemotherapy efficacy at the tumor cell level in prostate cancer (PC). Procedures: The effects of docetaxel and cabazitaxel on viable tumor cell number were explored in four PC cell lines. Cellular uptake of [F]FDG and [F]FCH was compared with the effects measured using sulforhodamine B (SRB) assay, cell counting and colony formation assay (CFA), as proximators of viable tumor cell number. Agreement between uptake and cell numbers was assessed by Bland-Altman plots. Results: [F]FCH uptake in all PC cell lines significantly correlated to the cell numbers surviving the respective drug concentrations. Bland-Altman analysis showed that [F]FDG uptake resulted in signal overestimation and higher variability after chemotherapy. Conclusions: [F]FCH uptake correlates well with viable tumor cell numbers remaining after docetaxel and cabazitaxel exposure. Radiolabeled choline is a potential response monitoring biomarker after chemotherapy for PC. [ABSTRACT FROM AUTHOR]

Abstract Purpose  To assess DOTATOC-affine somatostatin receptor expression in advanced prostate cancer and its bone metastases with regard to DOTATOC-mediated receptor therapies, using a Ga-68–DOTATOC PET/CT. Procedures  Twenty consecutive patients with advanced prostate cancer underwent bone scintigraphy, followed by Ga-68–DOTATOC PET/CT within 3 weeks. Through side-by-side comparison with bone scintigraphy, the number of visible bone metastases on PET was determined. In addition, in cases of visible metastases, the maximum standard uptake value (SUVmax) of Ga-68–DOTATOC was measured in the metastases and in normal bone. In patients who did not undergo a prostatectomy (n = 12), the SUVmax was additionally measured in the prostate and in adjacent tissue. For focal lesions, the difference in SUVmax (ΔSUVmax) between the metastases and normal bone was calculated. For patients still having their prostate, a ΔSUVmax between the prostate and its adjacent tissue was calculated. Results  Sixty four of 216 metastases (30%) were visible in 13 patients with focal metastases. Of six patients with diffuse metastases (superscan), one showed diffuse metastases, three showed a total of ten focal metastases, and two showed no correlate on PET. One patient with a neuroendocrine prostate cancer showed no correlate on PET. The maximum ΔSUVmax between metastases and normal bone was 4.9 (mean = 1.6 ± 0.9) and between the prostate and adjacent tissue 5.9 (mean = 2.8 ± 1.6). Conclusions  In prostate cancer and its bone metastases, DOTATOC-affine somatostatin receptors (subtype 2 and 5) can be visualized with Ga-68–DOTATOC PET/CT. But their expression is so weak that other conjugates should be tested for receptor-mediated therapies which are better at addressing the prostate cancer-specific somatostatin receptor subtypes 1 and 4—or even other receptors. [ABSTRACT FROM AUTHOR]

Aim: F-18 fluor choline-positron emission tomography/computed tomography (FCH-PET/CT) has emerged as a new diagnostic tool for the imaging of prostate cancer. In this study, we have evaluated the potential role of FCH-PET/CT for the assessment of bone metastases in patients with prostate cancer. Furthermore, we assessed the pattern of metabolic uptake by FCH in relation to morphologic changes on CT.Methods: Seventy men with biopsy-proven prostate cancer underwent FCH-PET/CT for preoperative staging or follow-up evaluation. Thirty-two patients were evaluated preoperatively, and 38 patients were referred for postoperative evaluation of suspected recurrence or progression based on clinical algorithms. PET imaging consisted of a dynamic PET/CT acquisition of the pelvic region during 8 min (1 min frames) starting 1 min after i.v. injection of 4.07 MBq/kg/bw FCH, which was followed immediately by a semi-whole body acquisition.Results: Overall, 262 lesions showed increased uptake on FCH-PET. Two hundred ten lesions (210 of 262) were interpreted as bone metastases. The mean of maximum standardized uptake value (SUV(max)) in all malignant lesions was 8.1 +/- 3.9. Forty-nine lesions (24%) had no detectable morphological changes on CT-probably due to bone marrow metastases. Fifty-six sclerotic lesions (having a Hounsfield unit (HU) level of more than 825) were interpreted as highly suspicious for metastatic bone disease on CT and/or other imaging modalities such as the bone scan, but showed no FCH uptake. There was a significant correlation between tracer uptake as assessed by SUV and the density of sclerotic lesions by HU (r = -0.52, p < 0.001). The sensitivity, specificity, and accuracy of FCH-PET/CT in detecting bone metastases from prostate cancer was 79%, 97%, and 84%, respectively.Conclusion: FCH-PET/CT showed promising results for the early detection of bone metastases in prostate cancer patients. We have found that a HU level of above 825 is associated with an absence of FCH uptake. Almost all of the FCH-negative sclerotic lesions were detected in patients who were under hormone therapy, which raises the possibility that these lesions might no longer be viable. However, clarification and the prognostic value of such lesions require further research. [ABSTRACT FROM AUTHOR]