Publications by authors named "Annibale Versari"

108 Publications

State of the art of F-FDG PET/CT application in inflammation and infection: a guide for image acquisition and interpretation.

Clin Transl Imaging 2021 Jul 10:1-41. Epub 2021 Jul 10.

Regional Center of Nuclear Medicine, Department of Translational Research and Advanced Technologies in Medicine, University of Pisa, Pisa, Italy.

Aim: The diagnosis, severity and extent of a sterile inflammation or a septic infection could be challenging since there is not one single test able to achieve an accurate diagnosis. The clinical use of 18F-fluorodeoxyglucose ([F]FDG) positron emission tomography/computed tomography (PET/CT) imaging in the assessment of inflammation and infection is increasing worldwide. The purpose of this paper is to achieve an Italian consensus document on [F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases, such as osteomyelitis (OM), prosthetic joint infections (PJI), infective endocarditis (IE), prosthetic valve endocarditis (PVE), cardiac implantable electronic device infections (CIEDI), systemic and cardiac sarcoidosis (SS/CS), diabetic foot (DF), fungal infections (FI), tuberculosis (TBC), fever and inflammation of unknown origin (FUO/IUO), pediatric infections (PI), inflammatory bowel diseases (IBD), spine infections (SI), vascular graft infections (VGI), large vessel vasculitis (LVV), retroperitoneal fibrosis (RF) and COVID-19 infections.

Methods: In September 2020, the inflammatory and infectious diseases focus group (IIFG) of the Italian Association of Nuclear Medicine (AIMN) proposed to realize a procedural paper about the clinical applications of [F]FDG PET/CT or PET/MRI in inflammatory and infectious diseases. The project was carried out thanks to the collaboration of 13 Italian nuclear medicine centers, with a consolidate experience in this field. With the endorsement of AIMN, IIFG contacted each center, and the pediatric diseases focus group (PDFC). IIFG provided for each team involved, a draft with essential information regarding the execution of [F]FDG PET/CT or PET/MRI scan (i.e., indications, patient preparation, standard or specific acquisition modalities, interpretation criteria, reporting methods, pitfalls and artifacts), by limiting the literature research to the last 20 years. Moreover, some clinical cases were required from each center, to underline the teaching points. Time for the collection of each report was from October to December 2020.

Results: Overall, we summarized 291 scientific papers and guidelines published between 1998 and 2021. Papers were divided in several sub-topics and summarized in the following paragraphs: clinical indications, image interpretation criteria, future perspectivess and new trends (for each single disease), while patient preparation, image acquisition, possible pitfalls and reporting modalities were described afterwards. Moreover, a specific section was dedicated to pediatric and PET/MRI indications. A collection of images was described for each indication.

Conclusions: Currently, [F]FDG PET/CT in oncology is globally accepted and standardized in main diagnostic algorithms for neoplasms. In recent years, the ever-closer collaboration among different European associations has tried to overcome the absence of a standardization also in the field of inflammation and infections. The collaboration of several nuclear medicine centers with a long experience in this field, as well as among different AIMN focus groups represents a further attempt in this direction. We hope that this document will be the basis for a "common nuclear physicians' language" throughout all the country.

Supplementary Information: The online version contains supplementary material available at 10.1007/s40336-021-00445-w.
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http://dx.doi.org/10.1007/s40336-021-00445-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271312PMC
July 2021

Prognostic Impact of Muscle Quantity and Quality and Fat Distribution in Diffuse Large B-Cell Lymphoma Patients.

Front Nutr 2021 7;8:620696. Epub 2021 May 7.

Clinical Nutrition Unit, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy.

Baseline CT scans of 116 patients (48% female, median 64 years) with diffuse large B-cell lymphoma (DLBCL) were retrospectively reviewed to investigate the prognostic role of sarcopenia and fat compartment distributions on overall survival (OS), progression-free survival (PFS), and early therapy termination. Skeletal muscle index (SMI), skeletal muscle density (SMD), and intermuscular adipose tissue (IMAT) were quantified at the level of the third lumbar vertebra (L3) and proximal thigh (PT). Low L3-SMD, but not low L3-SMI, was associated with early therapy termination ( = 0.028), shorter OS (HR = 6.29; 95% CI = 2.17-18.26; < 0.001), and shorter PFS (HR = 2.42; 95% CI = 1.26-4.65; = 0.008). After correction for sex, International Prognostic Index (IPI), BMI, and R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), low L3-SMD remained associated with poor OS (HR = 3.54; 95% CI = 1.10-11.40; = 0.034) but not with PFS. Increased PT-IMAT was prognostic for poor OS and PFS after correction for sex, IPI, BMI, and R-CHOP therapy (HR = 1.35; CI = 1.03-1.7; = 0.03, and HR = 1.30; CI = 1.04-1.64; = 0.024, respectively). Reduced muscle quality (SMD) and increased intermuscular fat (IMAT), rather than low muscle quantity (SMI), are associated with poor prognosis in DLBCL, when measured at the L3 level, and particularly at the level of the proximal thigh. The proximal thigh represents a novel radiological landmark to study body composition.
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http://dx.doi.org/10.3389/fnut.2021.620696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138563PMC
May 2021

The prognostic power of 18F-FDG PET/CT extends to estimating systemic treatment response duration in metastatic castration-resistant prostate cancer (mCRPC) patients.

Prostate Cancer Prostatic Dis 2021 May 19. Epub 2021 May 19.

Nuclear Medicine, Spedali Civili of Brescia and University of Brescia, Brescia, Italy.

Background: We aimed to test whether the prognostic value of 18 F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) in metastatic castration-resistant prostate cancer (mCRPC) extends to the estimation of systemic treatment response duration.

Methods: mCRPC patients submitted to FDG-PET/CT in four Italian centers from 2005 to 2020 were retrospectively enrolled. Clinical and biochemical data at the time of imaging were collected, and SUV max of the hottest lesion, total metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. The correlation between PET- and biochemical-derived parameters with Overall Survival (OS) was analysed. The prediction of treatment response duration was assessed in the subgroup submitted to FDG-PET/CT in the six months preceding Chemotherapy (namely Docetaxel or Cabazitaxel, 24 patients) or Androgen-Receptor Targeted Agents (ARTA, namely Abiraterone or Enzalutamide, 20 patients) administration.

Results: We enrolled 114 mCRPC patients followed-up for a median interval lasting 15 months. While at univariate analysis, prostate-specific antigen (PSA), Alkaline Phosphatase (ALP), MTV, and TLG were associated with OS, at the multivariate Cox regression analysis, the sole MTV could independently predict OS (p < 0.0001). In the subgroup submitted to FDG-PET/CT before the systemic treatment initiation, PSA and TLG could also predict treatment response duration independently (p < 0.05). Of note, while PSA could not indicate the best treatment choice, lower TLG was associated with higher success rates for ARTA but had no impact on chemotherapy efficacy.

Conclusions: FDG-PET/CT's prognostic value extends to predicting treatment response duration in mCRPC, thus potentially guiding the systemic treatment selection.
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http://dx.doi.org/10.1038/s41391-021-00391-8DOI Listing
May 2021

Resolution of vascular inflammation in patients with new-onset giant cell arteritis: data from the RIGA study.

Rheumatology (Oxford) 2021 Apr 8. Epub 2021 Apr 8.

Rheumatology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy.

Objectives: Efficacy evaluation of giant cell arteritis (GCA) treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT.

Methods: Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with methotrexate (MTX) or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients.

Results: We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX, and 19 with TOC. PETVAS decreased from 18.9-8.0 units at follow-up in the overall population (p< 0.001). PETVAS changes were numerically higher in patients receiving MTX (-12.3 units) or TOC (-11.7 units) compared with PRED (-8.7). Mean cumulative prednisolone dosages were 5637, 4418, and 2984 mg in patients treated with PRED, MTX, and TOC (p= 0.002). Risk ratios for glucocorticoid discontinuation at the time of follow-up PET/CT were 6.77 (95%CI 1.01-45.29; p= 0.049) and 16.25 (95%CI 2.60-101.73; p= 0.003) for MTX and TOC users compared with PRED users.

Conclusion: Treatment of LV-GCA inhibits vascular inflammation in the aorta and its major branches. While similar control of vascular inflammation was achieved with PRED, MTX, and TOC treatments, TOC showed a strong glucocorticoid sparing effect, supporting the concept of initial combination therapy.
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http://dx.doi.org/10.1093/rheumatology/keab332DOI Listing
April 2021

Ga-DOTATOC PET/CT-Based Radiomic Analysis and PRRT Outcome: A Preliminary Evaluation Based on an Exploratory Radiomic Analysis on Two Patients.

Front Med (Lausanne) 2020 26;7:601853. Epub 2021 Jan 26.

Nuclear Medicine Unit, Department of Medical Sciences, University of Turin, Turin, Italy.

This work aims to evaluate whether the radiomic features extracted by 68Ga-DOTATOC-PET/CT of two patients are associated with the response to peptide receptor radionuclide therapy (PRRT) in patients affected by neuroendocrine tumor (NET). This is a pilot report in two NET patients who experienced a discordant response to PRRT (responder vs. non-responder) according to RECIST1.1. The patients presented with liver metastasis from the rectum and pancreas G3-NET, respectively. Whole-body total-lesion somatostatin receptor-expression (TLSREwb-50) and somatostatin receptor-expressing tumor volume (SRETV wb-50) were obtained in pre- and post-PRRT PET/CT. Radiomic analysis was performed, extracting 38 radiomic features (RFs) from the patients' lesions. The Mann-Whitney test was used to compare RFs in the responder patient vs. the non-responder patient. Pearson correlation and principal component analysis (PCA) were used to evaluate the correlation and independence of the different RFs. TLSREwb-50 and SRETVwb-50 modifications correlate with RECIST1.1 response. A total of 28 RFs extracted on pre-therapy PET/CT showed significant differences between the two patients in the Mann-Whitney test ( < 0.05). A total of seven second-order features, with poor correlation with SUVmax and PET volume, were identified by the Pearson correlation matrix. Finally, the first two PCA principal components explain 83.8% of total variance. TLSREwb-50 and SRETVwb-50 are parameters that might be used to predict and to assess the PET response to PRRT. RFs might have a role in defining inter-patient heterogeneity and in the prediction of therapy response. It is important to implement future studies with larger and more homogeneous patient populations to confirm the efficacy of these biomarkers.
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http://dx.doi.org/10.3389/fmed.2020.601853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870479PMC
January 2021

Prevalence of interstitial pneumonia suggestive of COVID-19 at F-FDG PET/CT in oncological asymptomatic patients in a high prevalence country during pandemic period: a national multi-centric retrospective study.

Eur J Nucl Med Mol Imaging 2021 08 9;48(9):2871-2882. Epub 2021 Feb 9.

Unit of Nuclear Medicine, Department of Radiology and Clinical Radiotherapy, SS Annunziata Hospital, Chieti, Italy.

Purpose: To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus.

Methods: This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January-February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET.

Results: Overall, [F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1).

Conclusions: A significant increase of interstitial pneumonia incidentally detected with [F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management.
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http://dx.doi.org/10.1007/s00259-021-05219-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871520PMC
August 2021

Standardization of F-FDG-PET/CT According to Deauville Criteria for Metabolic Complete Response Definition in Newly Diagnosed Multiple Myeloma.

J Clin Oncol 2021 01 5;39(2):116-125. Epub 2020 Nov 5.

Nuclear Medicine Department, Nantes University Hospital, CRCINA INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France.

Purpose: F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is currently the standard technique to define minimal residual disease (MRD) status outside the bone marrow (BM) in patients with multiple myeloma (MM). This study aimed to define criteria for PET complete metabolic response after therapy, jointly analyzing a subgroup of newly diagnosed transplantation-eligible patients with MM enrolled in two independent European randomized phase III trials (IFM/DFCI2009 and EMN02/HO95).

Patients And Methods: Two hundred twenty-eight patients were observed for a median of 62.9 months. By study design, PET/CT scans were performed at baseline and before starting maintenance (premaintenance [PM]). The five-point Deauville scale (DS) was applied to describe BM (BM score [BMS]) and focal lesion (FL; FL score [FS]) uptake and tested a posteriori in uni- and multivariable analyses for their impact on clinical outcomes.

Results: At baseline, 78% of patients had FLs (11% extramedullary), 80% with an FS ≥ 4. All patients had BM diffuse uptake (35.5% with BMS ≥ 4). At PM, 31% of patients had visually detectable FLs (2% extramedullary), 24% and 67.7% of them with an FS of 3 and ≥ 4, respectively. At PM, 98% of patients retained residual BM diffuse uptake, which was significantly lower than at baseline (mainly between BMS 2 and 3, BMS was ≥ 4 in only 8.7% of patients). By both uni- and multivariable analysis, FS and BMS < 4 were associated with prolonged progression-free survival (PFS) and overall survival (OS) at PM (OS: hazard ratio [HR], 0.6 and 0.47, respectively; PFS: HR, 0.36 and 0.24, respectively).

Conclusion: FL and BM FDG uptake lower than the liver background after therapy was an independent predictor for improved PFS and OS and can be proposed as the standardized criterion of PET complete metabolic response, confirming the value of the DS for patients with MM.
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http://dx.doi.org/10.1200/JCO.20.00386DOI Listing
January 2021

Uncertainty analysis of tumour absorbed dose calculations in molecular radiotherapy.

EJNMMI Phys 2020 Oct 12;7(1):63. Epub 2020 Oct 12.

Medical Physics Unit, Azienda Unità Sanitaria Locale di Reggio Emilia - IRCCS, Reggio Emilia, Italy.

Background: Internal dosimetry evaluation consists of a multi-step process ranging from imaging acquisition to absorbed dose calculations. Assessment of uncertainty is complicated and, for that reason, it is commonly ignored in clinical routine. However, it is essential for adequate interpretation of the results. Recently, the EANM published a practical guidance on uncertainty analysis for molecular radiotherapy based on the application of the law of propagation of uncertainty. In this study, we investigated the overall uncertainty on a sample of a patient following the EANM guidelines. The aim of this study was to provide an indication of the typical uncertainties that may be expected from performing dosimetry, to determine parameters that have the greatest effect on the accuracy of calculations and to consider the potential improvements that could be made if these effects were reduced.

Results: Absorbed doses and the relative uncertainties were calculated for a sample of 49 patients and a total of 154 tumours. A wide range of relative absorbed dose uncertainty values was observed (14-102%). Uncertainties associated with each quantity along the absorbed dose calculation chain (i.e. volume, recovery coefficient, calibration factor, activity, time-activity curve fitting, time-integrated activity and absorbed dose) were estimated. An equation was derived to describe the relationship between the uncertainty in the absorbed dose and the volume. The largest source of error was the VOI delineation. By postulating different values of FWHM, the impact of the imaging system spatial resolution on the uncertainties was investigated.

Discussion: To the best of our knowledge, this is the first analysis of uncertainty in molecular radiotherapy based on a cohort of clinical cases. Wide inter-lesion variability of absorbed dose uncertainty was observed. Hence, a proper assessment of the uncertainties associated with the calculations should be considered as a basic scientific standard. A model for a quick estimate of uncertainty without implementing the entire error propagation schema, which may be useful in clinical practice, was presented. Ameliorating spatial resolution may be in future the key factor for accurate absorbed dose assessment.
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http://dx.doi.org/10.1186/s40658-020-00328-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550507PMC
October 2020

Use of octreotide long acting repeatable (LAR) as second-line therapy in advanced neuroendocrine tumors in different clinical settings: an Italian Delphi survey.

Expert Opin Pharmacother 2020 Dec 29;21(18):2317-2324. Epub 2020 Sep 29.

Nuclear Medicine Unit, AUSL-IRCCS of Reggio Emilia , Reggio Emilia, Italy.

Background: Somatostatin receptor ligands including octreotide LAR are first-line therapy in locally advanced or metastatic NETs that are nonresectable and well differentiated and are recommended as first-line therapy in functioning and in G1/low G2 nonfunctioning NETs. However, several questions remain that are not adequately addressed in current guidelines regarding its use in clinical scenarios in which the tumor progresses. These include use of nonconventional doses or schedules of octreotide LAR in tumors with hormonal symptoms or showing clinical-radiological progression, administration in combination with everolimus, peptide receptor radionuclide therapy, and chemotherapy, following first-line treatment with octreotide LAR.

Methods: An expert panel was gathered to obtain consensus using Delphi methodology on a series of statements regarding further administration of octreotide LAR after its use in first-line therapy in these settings in patients who experience disease progression.

Results: Consensus was reached for 8 of the 10 statements proposed in the above clinical scenarios; consensus was not achieved for two statements.

Conclusions: The present statements aim to fill current gaps in treatment guidelines by providing recommendations based on expert consensus in clinical settings in which patients progress following first-line therapy with octreotide LAR.
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http://dx.doi.org/10.1080/14656566.2020.1810237DOI Listing
December 2020

Comparison of different calculation techniques for absorbed dose assessment in patient specific peptide receptor radionuclide therapy.

PLoS One 2020 7;15(8):e0236466. Epub 2020 Aug 7.

Azienda Unità Sanitaria Locale di Reggio Emilia-IRCCS, Medical Physics Unit, Reggio Emilia, Italy.

Aim: The present work concerns the comparison of the performances of three systems for dosimetry in RPT that use different techniques for absorbed dose calculation (organ-level dosimetry, voxel-level dose kernel convolution and Monte Carlo simulations). The aim was to assess the importance of the choice of the most adequate calculation modality, providing recommendations about the choice of the computation tool.

Methods: The performances were evaluated both on phantoms and patients in a multi-level approach. Different phantoms filled with a 177Lu-radioactive solution were used: a homogeneous cylindrical phantom, a phantom with organ-shaped inserts and two cylindrical phantoms with inserts different for shape and volume. A total of 70 patients with NETs treated by PRRT with 177Lu-DOTATOC were retrospectively analysed.

Results: The comparisons were performed mainly between the mean values of the absorbed dose in the regions of interest. A general better agreement was obtained between Dose kernel convolution and Monte Carlo simulations results rather than between either of these two and organ-level dosimetry, both for phantoms and patients. Phantoms measurements also showed the discrepancies mainly depend on the geometry of the inserts (e.g. shape and volume). For patients, differences were more pronounced than phantoms and higher inter/intra patient variability was observed.

Conclusion: This study suggests that voxel-level techniques for dosimetry calculation are potentially more accurate and personalized than organ-level methods. In particular, a voxel-convolution method provides good results in a short time of calculation, while Monte Carlo based computation should be conducted with very fast calculation systems for a possible use in clinics, despite its intrinsic higher accuracy. Attention to the calculation modality is recommended in case of clinical regions of interest with irregular shape and far from spherical geometry, in which Monte Carlo seems to be more accurate than voxel-convolution methods.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236466PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413508PMC
September 2020

The role of 68Ga-DOTA derivatives PET-CT in patients with ectopic ACTH syndrome.

Endocr Connect 2020 Mar 1. Epub 2020 Mar 1.

C Scaroni, Endocrinology Unit, University of Padova Department of Medicine, Padova, Italy.

Introduction And Aim: Ectopic ACTH secretion (EAS) is mostly secondary to thoracic/abdominal neuroendocrine tumours (NETs), or small cell-lung carcinoma (SCLC). We studied the diagnostic accuracy of computed tomography (CT) with 68Ga-Dota derivatives (68Ga-SSTR) positron emission tomography (PET) in localizing ACTH-secreting tumor in patients with EAS.

Materials And Methods: 68Ga-SSTR-PET/CT was performed and compared with the nearest enhanced CT in 18 cases (16 primary and 2 recurrent neoplasms). Unspecific, indeterminate and false positive uptakes were assessed using conventional imaging, follow-up or histology.

Results: We diagnosed 13 thoracic (9 primary and 2 recurrent bronchial carcinoids, 2 SCLCs) and 1 abdominal (pancreatic NET) tumors. 8 ACTH-secreting tumors were promptly identified at EAS diagnosis ('overt', 4 pulmonary carcinoids with 2 recurrences, and 2 SCLC); 6 EAS have been discovered during the subsequent follow-up ('covert', 5 bronchial carcinoids and 1 pancreatic NET). At the time of EAS diagnosis, imaging was able to correctly detect the ACTH-secreting tumour in 8/18 cases (6 new diagnosis and 2 recurrences). During the follow-up, 6 out of initially 10 'occult' cases became 'covert'. At last available follow-up, CT and 68Ga-SSTR-PET/CT were able to diagnose respectively 11/18 and 12/18 ACTH-secreting tumours (respectively 11/14 and 12/14 considering only overt and covert cases). 4 cases have never been localized by conventional or nuclear imaging ('occult' EAS), despite an average follow up of 5 years.

Conclusions: The 68Ga-SSTR-PET/CT is useful in localizing EAS, especially to enhance positive prediction of the suggestive CT lesions and to detect occult neoplasms.
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http://dx.doi.org/10.1530/EC-20-0089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219142PMC
March 2020

Radiotherapy Planning and Molecular Imaging in Lung Cancer.

Curr Radiopharm 2020 ;13(3):204-217

Nuclear Medicine Unit, Azienda Unita Sanitaria Locale, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.

Introduction: In patients suitable for radical chemoradiotherapy for lung cancer, 18F-FDGPET/ CT is a proposed management to improve the accuracy of high dose radiotherapy. However, there is a high rate of locoregional failure in patients with locally advanced non-small cell lung cancer (NSCLC), probably due to the fact that standard dosing may not be effective in all patients. The aim of the present review was to address some criticisms associated with the radiotherapy image-guided in NSCLC.

Materials And Methods: A systematic literature search was conducted. Only published articles that met the following criteria were included: articles, only original papers, radiopharmaceutical ([18F]FDG and any tracer other than [18F]FDG), target, only specific for lung cancer radiotherapy planning, and experimental design (eventually "in vitro" studies were excluded). Peer-reviewed indexed journals, regardless of publication status (published, ahead of print, in press, etc.) were included. Reviews, case reports, abstracts, editorials, poster presentations, and publications in languages other than English were excluded. The decision to include or exclude an article was made by consensus and any disagreement was resolved through discussion.

Results: Hundred eligible full-text articles were assessed. Diverse information is now available in the literature about the role of FDG and new alternative radiopharmaceuticals for the planning of radiotherapy in NSCLC. In particular, the role of alternative technologies for the segmentation of FDG uptake is essential, although indeterminate for RT planning. The pros and cons of the available techniques have been extensively reported.

Conclusion: PET/CT has a central place in the planning of radiotherapy for lung cancer and, in particular, for NSCLC assuming a substantial role in the delineation of tumor volume. The development of new radiopharmaceuticals can help overcome the problems related to the disadvantage of FDG to accumulate also in activated inflammatory cells, thus improving tumor characterization and providing new prognostic biomarkers.
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http://dx.doi.org/10.2174/1874471013666200318144154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206193PMC
January 2020

18F-fluorodeoxyglucose positron emission tomography in malignant pleural mesothelioma: diagnostic and prognostic performance and its correlation to pathological results.

Interact Cardiovasc Thorac Surg 2020 04;30(4):593-596

Department of Nuclear Medicine, Azienda USL di Reggio Emilia-IRCCS, Reggio Emilia, Italy.

Although 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan has been generally validated in the staging of malignant pleural mesothelioma (MPM), its diagnostic and prognostic performances are not clearly established. Aiming to identify possible factors causing 18F-fluorodeoxyglucose PET/CT false-negative results and influencing prognosis in MPM patients, we analysed clinical, radiometabolic and pathological features in 141 MPM patients who underwent diagnostic 18F-fluorodeoxyglucose PET/CT scan (January 2009-July 2018) at 2 high-volume institutions. The Fisher's exact test and the Cox model were used in statistical analysis. Overall detection rate was 88.3% with 16 patients (11.6%) presenting with a standardized uptake value (SUV) max <2.5 (PET-negative). PET-negative cases were more frequently detected in older patients (P = 0.027) and early-stage tumours (33.3% false-negative in stage I and 40.0% false-negative in T1-tumours, with P = 0.014 both). Mean SUVmax value was higher in sarcomatoid (11.8 ± 4.6) and biphasic MPM (9.3 ± 7.0), rather than in epithelioid MPM (6.9 ± 3.8, P < 0.001). Concerning overall survival, SUVmax (both as continuous and as categorical variable) was found to be a prognostic factor, in addition to stage (P = 0.032) and histology (P = 0.014) as confirmed by multivariable analysis (hazard ratio 2.65, confidence interval 1.23-5.70; P < 0.001). In the light of such results, we highlight that a low fluorodeoxyglucose uptake might be observed in more than 10% MPMs, especially in early-stage tumours affecting elderly patients. Furthermore, high SUVmax values significantly correlated with a worse prognosis.
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http://dx.doi.org/10.1093/icvts/ivz303DOI Listing
April 2020

Texture analysis and multiple-instance learning for the classification of malignant lymphomas.

Comput Methods Programs Biomed 2020 Mar 23;185:105153. Epub 2019 Oct 23.

Medical Physics, Azienda USL-IRCCS di Reggio Emilia, Italy. Electronic address:

Background And Objectives: Malignant lymphomas are cancers of the immune system and are characterized by enlarged lymph nodes that typically spread across many different sites. Many different histological subtypes exist, whose diagnosis is typically based on sampling (biopsy) of a single tumor site, whereas total body examinations with computed tomography and positron emission tomography, though not diagnostic, are able to provide a comprehensive picture of the patient. In this work, we exploit a data-driven approach based on multiple-instance learning algorithms and texture analysis features extracted from positron emission tomography, to predict differential diagnosis of the main malignant lymphomas subtypes.

Methods: We exploit a multiple-instance learning setting where support vector machines and random forests are used as classifiers both at the level of single VOIs (instances) and at the level of patients (bags). We present results on two datasets comprising patients that suffer from four different types of malignant lymphomas, namely diffuse large B cell lymphoma, follicular lymphoma, Hodgkin's lymphoma, and mantle cell lymphoma.

Results: Despite the complexity of the task, experimental results show that, with sufficient data samples, some cancer subtypes, such as the Hodgkin's lymphoma, can be identified from texture information: in particular, we achieve a 97.0% of sensitivity (recall) and a 94.1% of predictive positive value (precision) on a dataset that consists in 60 patients.

Conclusions: The presented study indicates that texture analysis features extracted from positron emission tomography, combined with multiple-instance machine learning algorithms, can be discriminating for different malignant lymphomas subtypes.
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http://dx.doi.org/10.1016/j.cmpb.2019.105153DOI Listing
March 2020

A Gene Expression-based Model to Predict Metabolic Response After Two Courses of ABVD in Hodgkin Lymphoma Patients.

Clin Cancer Res 2020 01 23;26(2):373-383. Epub 2019 Oct 23.

Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

Purpose: Early response to ABVD, assessed with interim FDG-PET (iPET), is prognostic for classical Hodgkin lymphoma (cHL) and supports the use of response adapted therapy. The aim of this study was to identify a gene-expression profile on diagnostic biopsy to predict iPET positivity (iPET).

Experimental Design: Consecutive untreated patients with stage I-IV cHL who underwent iPET after two cycles of ABVD were identified. Expression of 770 immune-related genes was analyzed by digital expression profiling (NanoString Technology). iPET was centrally reviewed according to the five-point Deauville scale (DS 1-5). An iPET predictive model was derived by multivariate regression analysis and assessed in a validation set identified using the same inclusion criteria.

Results: A training set of 121 and a validation set of 117 patients were identified, with 23 iPET cases in each group. Sixty-three (52.1%), 19 (15.7%), and 39 (32.2%) patients had stage I-II, III, and IV, respectively. Diagnostic biopsy of iPET cHLs showed transcriptional profile distinct from iPET. Thirteen genes were stringently associated with iPET. This signature comprises two functionally stromal-related nodes. Lymphocytes/monocytes ratio (LMR) was also associated to iPET. In the training cohort a 5-gene/LMR integrated score predicted iPET [AUC, 0.88; 95% confidence interval (CI), 0.80-0.96]. The score achieved a 100% sensitivity to identify DS5 cases. Model performance was confirmed in the validation set (AUC, 0.68; 95% CI, 0.52-0.84). Finally, iPET score was higher in patients with event versus those without.

Conclusions: In cHL, iPET is associated with a genetic signature and can be predicted by applying an integrated gene-based model on the diagnostic biopsy.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-2356DOI Listing
January 2020

Treatment With 90Y/177Lu-DOTATOC in Patients With Metastatic Adrenocortical Carcinoma Expressing Somatostatin Receptors.

J Clin Endocrinol Metab 2020 03;105(3)

Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia. ASST Spedali Civili, Brescia, Italy.

Context: We investigated the role of Gallium 68 dodecanetetraacetic acid Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography/computed tomography (PET/CT) in detecting somatostatin receptors (SSTRs) in 19 patients with metastatic adrenocortical carcinoma (ACC) and explored the activity of yttrium-90/lutetium-177 (90Y/177Lu-DOTATOC) peptide receptor radionuclide therapy (PRRT).

Case Description And Methods: 68Ga uptake in metastatic sites was scored in terms of intensity and anatomical uptake distribution of standard uptake value (SUV). Tissue expression of SSTR2A and SSTR5 was also evaluated by immunohistochemistry (IHC) on primary tumors. Eight (42%) patients displayed radiometabolic uptake of any-grade intensity with focal and limited distribution. Two (11%) patients displayed strong uptake in multiple lesions and were treated with PRRT. Both obtained an overall disease control lasting 4 and 12 months, respectively.

Conclusions: ACC can express SSTRs as detected by IHC and 68Ga-DOTATOC PET. SSTRs-based PRRT may represent a potential treatment opportunity for a minority of patients with advanced ACC. This treatment modality deserves further investigation.
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http://dx.doi.org/10.1210/clinem/dgz091DOI Listing
March 2020

Imbalance between angiogenic and anti-angiogenic factors in sera from patients with large-vessel vasculitis.

Clin Exp Rheumatol 2020 Mar-Apr;38 Suppl 124(2):23-30. Epub 2019 Sep 17.

Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, and Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.

Objectives: To investigate serum levels of a panel of angiogenic inducers (VEGF, FGF-2, Angiopoietin 1, -2, soluble VCAM-1) and inhibitors (angiostatin, endostatin, pentraxin-3) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK), in order to gain further insights into the molecular mechanisms driving angiogenesis dysregulation in large-vessel vasculitis (LVV).

Methods: Sera were obtained from 33 TAK patients and 14 GCA patients and from two groups of age-matched normal controls (NC). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Angiogenic and anti-angiogenic factor serum levels were evaluated using commercial ELISA kits. Pentraxin 3 (PTX3) serum levels were evaluated by non-commercial ELISA, as already described.

Results: Among the angiogenic factors, only VEGF serum levels were significantly higher in TAK patients compared to NC. No difference was found between angiogenic factor levels in GCA patients compared to those detected in NC. Anti-angiogenic factor (Angiostatin, Endostatin, PTX3) serum levels were significantly higher in both GCA and TAK patients compared to NC. Significant associations were observed between VEGF and PTX3 levels and disease activity evaluated using PET scan and clinical indices. Cluster analysis based on PET scan scores in TAK patients showed significant ordered differences in VEGF and angiostatin serum levels. Indeed, we noted a progressive increase of VEGF and angiostatin from NC to the cluster including patients with the highest and more diffuse scan positivity.

Conclusions: Our overall results demonstrate a circulating molecular profile characterised by a prevailing expression of anti-angiogenic soluble factors.
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September 2020

Immuno-Imaging to Predict Treatment Response in Infection, Inflammation and Oncology.

J Clin Med 2019 May 14;8(5). Epub 2019 May 14.

Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 Groningen, The Netherlands.

Background: Molecular nuclear medicine plays a pivotal role for diagnosis in a preclinical phase, in genetically susceptible patients, for radio-guided surgery, for disease relapse evaluation, and for therapy decision-making and follow-up. This is possible thanks to the development of new radiopharmaceuticals to target specific biomarkers of infection, inflammation and tumour immunology.

Methods: In this review, we describe the use of specific radiopharmaceuticals for infectious and inflammatory diseases with the aim of fast and accurate diagnosis and treatment follow-up. Furthermore, we focus on specific oncological indications with an emphasis on tumour immunology and visualizing the tumour environment.

Results: Molecular nuclear medicine imaging techniques get a foothold in the diagnosis of a variety of infectious and inflammatory diseases, such as bacterial and fungal infections, rheumatoid arthritis, and large vessel vasculitis, but also for treatment response in cancer immunotherapy.

Conclusion: Several specific radiopharmaceuticals can be used to improve diagnosis and staging, but also for therapy decision-making and follow-up in infectious, inflammatory and oncological diseases where immune cells are involved. The identification of these cell subpopulations by nuclear medicine techniques would provide personalized medicine for these patients, avoiding side effects and improving therapeutic approaches.
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http://dx.doi.org/10.3390/jcm8050681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571748PMC
May 2019

Cu and fluorescein labeled anti-miRNA peptide nucleic acids for the detection of miRNA expression in living cells.

Sci Rep 2019 03 4;9(1):3376. Epub 2019 Mar 4.

Nuclear Medicine Unit, Oncology and Advanced Technologies Department, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42123, Reggio Emilia, Italy.

MiRNAs are single stranded RNAs of 18-22 nucleotides. They are promising diagnostic and prognostic markers for several pathologies including tumors, neurodegenerative, cardiovascular and autoimmune diseases. In the present work the development and characterization of anti-miRNA radiolabeled probes based on peptide nucleic acids (PNAs) for potential non-invasive molecular imaging in vivo of giant cell arteritis are described. MiR-146a and miR-146b-5p were selected as targets because they have been found up-regulated in this disease. Anti-miR and scramble PNAs were synthesized and linked to carboxyfluorescein or DOTA. DOTA-anti-miR PNAs were then labelled with copper-64 (Cu) to function as non-invasive molecular imaging tools. The affinity of the probes for the targets was assessed in vitro by circular dichroism and melting temperature. Differential uptake of fluorescein and Cu labeled anti-miRNA probes was tested on BCPAP and A549 cell lines, expressing different levels of miR-146a and -146b-5p. The experiments showed that the anti-miR-146a PNAs were more effective than the anti-miR-146b-5p PNAs. Anti-miR-146a PNAs could bind both miR-146a and miR-146b-5p. The uptake of fluorescein and Cu labeled anti-miR-146a PNAs was higher than that of the negative control scramble PNAs in miRNA expressing cells in vitro. Cu-anti-miR-146a PNAs might be further investigated for non-invasive PET imaging of miR-146 overexpressing diseases.
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http://dx.doi.org/10.1038/s41598-018-35800-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399270PMC
March 2019

Diagnostic performances of 68Ga-DOTATOC versus 18Fluorodeoxyglucose positron emission tomography in pulmonary carcinoid tumours and interrelationship with histological features.

Interact Cardiovasc Thorac Surg 2019 06;28(6):957-960

Unit of Nuclear Medicine, Azienda Unità Sanitaria Locale-IRCCS, Reggio Emilia, Italy.

Few data are available about radio-receptorial positron emission tomography (PET) results by the use of 68Ga-DOTA-peptides in pulmonary carcinoid tumours. In this study, we retrospectively analysed 68Ga-DOTATOC/PET and 18Fluorodeoxyglucose (FDG) PET diagnostic performances in 62 pulmonary carcinoids (occurring in 57 patients) and interrelationship with histological features. All patients underwent at least 1 PET/computed tomography: 26 patients received 68Ga-DOTATOC, 52 patients had 18F-FDG and 20 patients received both techniques. There were 55 typical carcinoids and 7 atypical carcinoids. 68Ga-DOTATOC/PET recorded an 88.4% overall detection rate (DR) (meanSUVmax: 15.5); 18F-FDG/PET a DR of 53.8% (meanSUVmax: 3.2). When adopted a maximum standardized uptake value-threshold of 1.5, DRs of 68Ga-DOTATOC and 18F-FDG/PET increased to 100% and 80.8%, respectively. Moreover, DRs in both techniques vary considerably according to histology with 68Ga-DOTATOC/PET having better performances in typical carcinoids than in atypical carcinoids (DR: 91.7% vs 50.0%, P = 0.076). We also observed a significant correlation between a low number of mitoses (<2/10 high-power field) and 68Ga-DOTATOC/PET-positivity (P = 0.004), and an association trend (P = 0.076) between necrosis and 68Ga-DOTATOC/PET-negativity. In conclusion, 68Ga-DOTATOC had better diagnostic performances than 18F-FDG/PET in detecting pulmonary carcinoids. DRs of both techniques remarkably varied according to histology with 68Ga-DOTATOC/PET performing at its best in typical carcinoids, whereas 18F-FDG/PET did the same in atypical carcinoids.68Ga-DOTATOC/PET results were presumably associated with the number of mitoses and the presence of necrosis.
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http://dx.doi.org/10.1093/icvts/ivz009DOI Listing
June 2019

Partial volume effect of SPECT images in PRRT with 177Lu labelled somatostatin analogues: A practical solution.

Phys Med 2019 Jan 8;57:153-159. Epub 2019 Jan 8.

Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Medical Physics Unit, Reggio Emilia, Italy.

Background: At present activity quantification is one of the most critical step in dosimetry calculation, and Partial Volume Effect (PVE) one of the most important source of error. In recent years models based upon phantoms that incorporate hot spheres have been used to establish recovery models. In this context the goal of this study was to point out the most critical issues related to PVE and to establish a model closer to a biological imaging environment.

Methods: Two different phantoms, filled with a Lu solution, were used to obtain the PVE Recovery Coefficients (RCs): a phantom with spherical inserts and a phantom with organ-shaped inserts. Two additional phantoms with inserts of various geometrical shapes and an anthropomorphic phantom were acquired to compare the real activities to predicted values after PVE correction.

Results: The RCs versus volume of the inserts produced two different curves, one for the spheres and one for the organs. After PVE correction, accuracy on activity quantification averaged over all inserts of three test phantoms passed from -26% to 1.3% (from 26% to 10% for absolute values).

Conclusion: RCs is a simple method for PVE correction easily applicable in clinical routine. The use of two different models for organs and lesions has permitted to closely mimic the situation in a living subject. A marked improvement in the quantification of activity was observed when PVE correction was adopted, even if further investigations should be performed for more accurate models of PVE corrections.
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http://dx.doi.org/10.1016/j.ejmp.2018.12.029DOI Listing
January 2019

Interim analysis of the REASSURE (Radium-223 alpha Emitter Agent in non-intervention Safety Study in mCRPC popUlation for long-teRm Evaluation) study: patient characteristics and safety according to prior use of chemotherapy in routine clinical practice.

Eur J Nucl Med Mol Imaging 2019 May 12;46(5):1102-1110. Epub 2019 Jan 12.

Royal Marsden Hospital, London, UK.

Purpose: REASSURE is a global, prospective, non-interventional study to assess long-term safety of radium-223 in patients with bone metastatic castration-resistant prostate cancer. Here we report an interim analysis of patients according to previous use of chemotherapy.

Methods: Radium-223 was administered in routine clinical practice. Interim safety analysis was planned after enrolment of the first 600 patients. Patient characteristics and safety data by previous administration of chemotherapy (docetaxel and/or cabazitaxel) were investigated.

Results: This interim analysis included 583 patients. Median duration of observation was 7 months (range, 0-20). Nineteen patients treated with concomitant chemotherapy were excluded, 564 (97%) were eligible for exploratory analysis according to prior use of chemotherapy; 190 (34%) had previously received and completed chemotherapy, and 374 (66%) had not. In the prior versus no prior chemotherapy group, a higher proportion of patients had an Eastern Cooperative Oncology Group performance status of ≥2 (22% vs 11%) and > 20 metastatic lesions (26% vs 15%), median alkaline phosphatase (162.0 vs 115.0 U/L) and prostate-specific antigen (132.0 vs 40.2 ng/mL) levels were higher, and a lower proportion completed 6 radium-223 injections (45% vs 63%). Drug-related treatment-emergent adverse events (TEAEs) occurred in 63 and 48%, and haematological drug-related TEAEs in 21 and 9% of patients who had or had not previously received chemotherapy. Four drug-related deaths were reported, all in the prior chemotherapy group.

Conclusions: The short-term safety profile of radium-223 in routine clinical practice was comparable to other clinical studies, irrespective of prior chemotherapy use. Haematological TEAEs occurred more frequently in the prior chemotherapy group, presumably due to decreased bone marrow function as a consequence of more advanced disease and prior exposure to cytotoxic therapy. Patients who had not previously received chemotherapy appeared to have a lower burden of disease at baseline, and a lower proportion discontinued radium-223 treatment.
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http://dx.doi.org/10.1007/s00259-019-4261-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451709PMC
May 2019

Aortic dilatation in patients with large vessel vasculitis: A longitudinal case control study using PET/CT.

Semin Arthritis Rheum 2019 06 12;48(6):1074-1082. Epub 2018 Oct 12.

Rheumatology Unit, Azienda Unità Sanitaria Locale Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy; University of Modena and Reggio Emilia, Modena, Italy. Electronic address:

Objective: To evaluate aortic diameter and predictors of aortic dilatation using FDG-PET/CT in a longitudinally followed cohort of patients with large vessel vasculitis (LVV) compared with controls.

Methods: All consecutive patients with LVV who underwent at least 2 PET/CT scans between January 2008 and May 2015 were included. The first and last PET/CT study was evaluated by a radiologist and a nuclear medicine physician. Diameter and FDG uptake of the aorta was measured at 4 different levels: ascending, descending thoracic, suprarenal and infrarenal abdominal aorta. Twenty-nine age- and sex-matched patients with lymphoma who underwent at least 2 PET/CT scans in the same time interval were selected as controls.

Results: 93 patients with LVV were included in the study. In the time interval between first and last PET/CT study (median time 31 months), the diameter of the ascending, descending thoracic and suprarenal abdominal aorta significantly increased in LVV patients but not in controls. At last PET/CT, patients with LVV compared with controls had higher diameter of ascending [35.41 (5.54) vs 32.97 (4.11) mm, p = 0.029], descending thoracic [28.42 (4.82) vs 25.72 (3.55) mm, p = 0.007] and suprarenal abdominal aorta, mean [25.34 (7.01) vs 22.16 (3.26) mm, p = 0.005] and more frequently had aortic dilatation [19% vs 3%, p = 0.023]. Significant predictors of aortic dilatation were male sex [OR 7.27, p = 0.001] and, only for GCA, hypertension [OR 6.30, p = 0.031]. Finally, GCA patients with aortic FDG uptake grade 3 at first PET/CT, compared to those with aortic FDG uptake ≤2, had significantly higher aortic diameter.

Conclusions: Patients with LVV are at increased risk of aortic dilatation compared with age- and sex-matched controls. Significant predictors of aortic dilatation are male sex and, only for GCA, hypertension. GCA patients with aortic FDG uptake grade 3 are at increased risk of aortic dilatation.
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http://dx.doi.org/10.1016/j.semarthrit.2018.10.003DOI Listing
June 2019

F-FDG and Ga-somatostatin analogs PET/CT in patients with Merkel cell carcinoma: a comparison study.

EJNMMI Res 2018 Jul 21;8(1):64. Epub 2018 Jul 21.

Department of Diagnostic Imaging, Radiation Oncology and Hematology, Institute of Nuclear Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168, Roma, Italia.

Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor. Currently, F-fluoro-deoxy-glucose (F-FDG) PET/CT is the functional imaging modality of choice. Few data are available on the use of Ga-somatostatin analogs. The aim of our study was to evaluate and compare the diagnostic performance of F-FDG and Ga-somatostatin analog PET/CT in MCC patients.

Results: Fifteen patients (12 males, 3 females; median age 73 years; range 41-81 years) with histologically proven MCC (4 with unknown primary lesion) who underwent both F-FDG and Ga-somatostatin analog PET/CT for staging, re-staging, or treatment response assessment were retrospectively evaluated. Results of both studies were qualitatively analyzed and compared on a patient- and lesion-based analysis, using histology or clinical/radiological follow-up as reference standard for final diagnosis. According to final diagnosis, 8/15 patients had at least one MCC lesion and 7/15 had no evidence of disease. On a patient-based analysis, F-FDG and Ga-somatostatin analogs correctly classified as positive 8/8 (100% sensitivity) patients and as negative 6/7 (85.7% specificity) and 5/7 (71.4% specificity) patients, respectively, with no significant difference. On a lesion-based analysis, F-FDG detected 67/75 lesions (89%) and Ga-somatostatin analogs 69/75 (92%), with no significant difference. In four patients with unknown primary MCC, both tracers failed to identify the primary MCC site.

Conclusions: Our preliminary data suggest that F-FDG and Ga-somatostatin analog PET/CT provide good and equivalent diagnostic performance, adding interesting insights into the complex MCC biology. However, these results do not suggest that F-FDG PET/CT should be replaced by Ga-somatostatin receptor imaging, which should be performed in addition, according to clinical indication, to the perspective of "personalized medicine."
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http://dx.doi.org/10.1186/s13550-018-0423-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054830PMC
July 2018

Distribution patterns of 18F-fluorodeoxyglucose in large vessels of Takayasu's and giant cell arteritis using positron emission tomography.

Clin Exp Rheumatol 2018 Mar-Apr;36 Suppl 111(2):99-106. Epub 2018 May 18.

Rheumatology Unit, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, and Università di Modena e Reggio Emilia, Italy.

Objectives: To compare patterns of vascular involvement using 18F-fluorodeoxyglucose-positron emission tomography computed tomography (FDG PET/CT) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK).

Methods: A total of 130 consecutive 18F-FDG PET/CT scans performed during the disease course for evaluating disease activity in 15 GCA and 13 TAK patients were retrospectively examined by two nuclear physicians blinded to clinical data. Standardised uptake values (SUVmax) in 14 vascular districts including all the aortic segments and the main tributaries were measured. The average SUVmax value for each vascular district was also calculated. Principal component analysis (PCA) and agglomerative hierarchical cluster analysis (CA) were used to explore distribution patterns of vascular FDG uptake.

Results: The aortic segments showed the highest SUV max values among the different districts in both GCA and TAK. SUV max values measured in the different districts were significantly higher in GCA compared to TAK, except for the axillary arteries. Regarding thoracic and abdominal aorta, ascending aorta and aortic arch had the highest correlation in both vasculitis (p<0.0001). CA confirmed that carotid, axillary, subclavian, iliac and femoral arteries clustered with their contralateral counterpart in both vasculitis. The 3 components of thoracic aorta clustered with abdominal aorta in TAK, while aortic arch clustered only with ascending aorta, and descending and abdominal aorta grouped together with iliac and femoral arteries in GCA. PCA analysis identified 3 different components for TAK and GCA explaining 72% and 71% of the total variance respectively in these two vasculitis. Confirming CA, a component including the entire aortic district was identified in TAK, but not in GCA. Similar results in PCA using averaged data were observed.

Conclusions: Strong similarities, but also a subtle skewing in terms of distribution patterns of arterial involvement assessed by SUVmax values were observed between GCA and TAK.
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July 2018

Molecular Imaging of Inflammatory Arthritis and Related Disorders.

Semin Nucl Med 2018 05 10;48(3):277-290. Epub 2018 Jan 10.

Nuclear Medicine Unit, Faculty of Medicine and Psychology, Department of Medical-Surgical Sciences and Translational Medicine, "Sapienza" University, Roma, Italy.

Rheumatic disorders comprise a number of diseases that range from benign, mildly symptomatic degenerative disease to severe systemic disorders such as giant-cell vasculitis with dramatic consequences such as acute blindness. The former is relatively common, whereas the latter is rare. In between, commonly encountered disorders such as rheumatoid arthritis and the various spondyloarthritides, with or without peripheral enthesitis, are daily challenges for the caring physician. Clinical evaluation is of utmost importance and is constantly described under the form of specialist guidelines in all parts of the world. Objective assessment of inflammatory arthritis and related disorders is of interest both for the care of the individual patient and for the assessment of the effects of the many novel experimental therapies proposed in this field, most of them being very expensive. High-resolution ultrasound, CT and spectral CT, MRI using various sequences, and molecular imaging using either gamma camera imaging (including SPECT-CT) or PET-CT are all proposed for a better assessment of these diseases. This review focuses on the several nuclear medicine techniques that are or may become useful to helping provide better patient care in this field and is mainly oriented to inflammatory rheumatic disorders, excluding mechanical degenerative diseases.
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http://dx.doi.org/10.1053/j.semnuclmed.2017.12.005DOI Listing
May 2018

Prognostic model for high-tumor-burden follicular lymphoma integrating baseline and end-induction PET: a LYSA/FIL study.

Blood 2018 05 20;131(22):2449-2453. Epub 2018 Mar 20.

Lymphoma Study Association Imaging, Hôpitaux Universitaires Henri Mondor, Université Paris Est, Créteil, France.

Both total metabolic tumor volume (TMTV), computed on baseline positron emission tomography (PET), and end of induction (EOI) PET are imaging biomarkers showing promise for early risk stratification in patients with high-tumor-burden follicular lymphoma. A model was built incorporating these 2 factors in 159 patients from three prospective trials: 2 Lymphoma Study Association (LYSA) studies and 1 Fondazione Italiana Linfomi (FIL) trial. Median follow up was 64 months. High TMTV (>510 cm) and positive EOI PET were independent, significant risk factors for progression. Their combination stratified the population into 3 risk groups: patients with no risk factors (n = 102; 64%) had a 5-year progression-free survival (PFS) of 67% vs 33% (hazard ratio [HR], 2.9; 95% confidence interval [CI], 1.8-4.9) for patients with 1 risk factor (n = 44; 27%) and only 23% (HR, 4.6; 95% CI, 2.3-9.2) for patients with both risk factors (n = 13; 8%). 2-year PFS was respectively 90% vs 61% (HR, 4.8; 95% CI, 2.2-10.4) and 46% (HR, 8.1; 95%CI, 3.1-21.3). This model enhances the prognostic value of PET staging and response assessment, identifying a subset of patients with a very high risk of progression and early treatment failure at 2 years.
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http://dx.doi.org/10.1182/blood-2017-11-816298DOI Listing
May 2018

Effect of image registration on 3D absorbed dose calculations in Lu-DOTATOC peptide receptor radionuclide therapy.

Phys Med 2018 Jan 8;45:177-185. Epub 2018 Jan 8.

Department of Medical Physics, Velindre Cancer Centre, Cardiff, Wales, UK; School of Engineering, Cardiff University, Cardiff, Wales, UK.

Peptide receptor radionuclide therapy (PRRT) is an effective MRT (molecular radiotherapy) treatment, which consists of multiple administrations of a radiopharmaceutical labelled with Lu or Y. Through sequential functional imaging a patient specific 3D dosimetry can be derived. Multiple scans should be previously co-registered to allow accurate absorbed dose calculations. The purpose of this study is to evaluate the impact of image registration algorithms on 3D absorbed dose calculation. A cohort of patients was extracted from the database of a clinical trial in PRRT. They were administered with a single administration of Lu-DOTATOC. All patients underwent 5 SPECT/CT sequential scans at 1 h, 4 h, 24 h, 40 h, 70 h post-injection that were subsequently registered using rigid and deformable algorithms. A similarity index was calculated to compare rigid and deformable registration algorithms. 3D absorbed dose calculation was carried out with the Raydose Monte Carlo code. The similarity analysis demonstrated the superiority of the deformable registrations (p < .001). Average absorbed dose to the kidneys calculated using rigid image registration was consistently lower than the average absorbed dose calculated using the deformable algorithm (90% of cases), with percentage differences in the range [-19; +4]%. Absorbed dose to lesions were also consistently lower (90% of cases) when calculated with rigid image registration with absorbed dose differences in the range [-67.2; 100.7]%. Deformable image registration had a significant role in calculating 3D absorbed dose to organs or lesions with volumes smaller than 100 mL. Image based 3D dosimetry for Lu-DOTATOC PRRT is significantly affected by the type of algorithm used to register sequential SPECT/CT scans.
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http://dx.doi.org/10.1016/j.ejmp.2017.11.021DOI Listing
January 2018
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