State of the art of 18F-FDG PET/CT application in inflammation and infection: a guide for image acquisition and interpretation.

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 ([18F]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 [18F]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 [18F]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 [18F]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, [18F]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.

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

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 (p = 0.028), shorter OS (HR = 6.29; 95% CI = 2.17-18.26; p < 0.001), and shorter PFS (HR = 2.42; 95% CI = 1.26-4.65; p = 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; p = 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; p = 0.03, and HR = 1.30; CI = 1.04-1.64; p = 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.

Significance of inflammation restricted to adventitial/periadventitial tissue on temporal artery biopsy.

OBJECTIVE: To evaluate the characteristics and significance of inflammation restricted (RI) to the adventitial and/or periadventitial tissue on temporal artery biopsy (TAB). METHODS: We studied a retrospective cohort of 80 patients with RI, extending our earlier series of 39 patients. For comparison purposes, we collected the same data from 254 patients with transmural inflammation (TMI) and 81 TAB-negative patients. A review of the literature was also performed. RESULTS: A final diagnosis of giant cells arteritis (GCA) and/or polymyalgia rheumatica (PMR) was observed in 86% of patients with RI. Compared to TMI, GCA diagnosis was significantly less frequently observed in patients with RI and in those TAB-negative (p < 0.0001), while cranial manifestations were significantly less frequent (p = 0.001) and ESR and CRP values at diagnosis significantly reduced (p < 0.0001). PMR, permanent visual loss, and large vessel involvement at diagnosis were equally present in the 3 subgroups. The median duration of prednisone therapy, the cumulative prednisone dosages, and the relapse and long-term remission rates were similar between patients with GCA-RI and those with TMI. The positive likelihood ratios (LRs) of pathological evidence of RI at TAB for GCA or GCA/PMR diagnoses were 0.88 (CI, 0.61-1.27) and 1.15 (CI, 0.67-1.99), while that of inflammation limited to adventitia was 1.37 (CI, 0.59-3.19) and 3.77 (CI, 0.53-26.72). In the literature review, the positive LR of RI for GCA diagnosis was 0.92 (CI, 0.68-1.25). CONCLUSION: A large part of the patients with RI have GCA/PMR, however, the diagnostic value of RI for GCA diagnosis is not relevant.

Relapses and long-term remission in large vessel giant cell arteritis in northern Italy: Characteristics and predictors in a long-term follow-up study.

OBJECTIVE: To evaluate characteristics and predictors of relapses and long-term remission in an Italian cohort of patients with large-vessel (LV) giant cell arteritis (GCA). METHODS: We evaluated 87 consecutive patients with LV-GCA followed up at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for at least 2 years. Patients with relapses and long-term remission were compared to those without. A group of 34 patients with biopsy proven GCA without LV vasculitis (LVV) at diagnosis was considered for comparison. PATIENTS: 37 patients (42.5%) experienced one or more relapses. Nineteen (37.2%) of the 51 relapses were experienced during the first year after diagnosis. The majority of relapses occurred with doses of prednisone (PDN) ≤ 10 mg/day (74.5%). Polymyalgia rheumatica (PMR) (41.2%) and worsening at imaging of LVV (39.2%) were the most frequently observed relapsing manifestations. The total cumulative prednisone dose was significantly higher (p < 0.0001) and the total duration of PDN treatment longer (p < 0.0001) in relapsing patients compared to those without relapses. Relapsing patients had at diagnosis more frequently fever ≥ 38°C (p = 0.03) and visual manifestations (p = 0.03), and less frequently long-term remission (p = 0.002). In the multivariate model fever ≥ 38°C (HR 2.30, 95%CI:1.11-4.78) and total cumulative PDN dose (HR 1.18, 95%CI: 1.08-1.30) were significantly associated with an increased risk of relapses, while aortic arch involvement at imaging at diagnosis (HR 0.26, 95%CI: 0.11-0.59) and long-term remission (HR 0.27, 95%CI: 0.11-0.65) with a reduced risk. 35/84 patients (41.6%) experienced long-term remission. PMR and disease relapses were less frequently observed (p = 0.04 and p = 0.002, respectively), and the total cumulative prednisone dose was lower (p < 0.001) in patients with long-term remission compared to those without. In the multivariate model the presence of relapses (HR 0.21, 95%CI: 0.07-0.62) and the total cumulative PDN dose (HR 0.85, 95%CI: 0.77-0.95) were significantly negatively associated with long-term remission. CONCLUSION: In our cohort of patients with LV GCA we identified predictors of a relapsing course and long-term remission, which were observed in around half of the patients.

Radiotherapy Planning and Molecular Imaging in Lung Cancer.

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.

Molecular Imaging of Pulmonary Inflammation and Infection.

Infectious and inflammatory pulmonary diseases are a leading cause of morbidity and mortality worldwide. Although infrequently used in this setting, molecular imaging may significantly contribute to their diagnosis using techniques like single photon emission tomography (SPET), positron emission tomography (PET) with computed tomography (CT) or magnetic resonance imaging (MRI) with the support of specific or unspecific radiopharmaceutical agents. 18F-Fluorodeoxyglucose (18F-FDG), mostly applied in oncological imaging, can also detect cells actively involved in infectious and inflammatory conditions, even if with a low specificity. SPET with nonspecific (e.g., 67Gallium-citrate (67Ga citrate)) and specific tracers (e.g., white blood cells radiolabeled with 111Indium-oxine (111In) or 99mTechnetium (99mTc)) showed interesting results for many inflammatory lung diseases. However, 67Ga citrate is unfavorable by a radioprotection point of view while radiolabeled white blood cells scan implies complex laboratory settings and labeling procedures. Radiolabeled antibiotics (e.g., ciprofloxacin) have been recently tested, although they seem to be quite unspecific and cause antibiotic resistance. New radiolabeled agents like antimicrobic peptides, binding to bacterial cell membranes, seem very promising. Thus, the aim of this narrative review is to provide a comprehensive overview about techniques, including PET/MRI, and tracers that can guide the clinicians in the appropriate diagnostic pathway of infectious and inflammatory pulmonary diseases.

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

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.

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

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.

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

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.

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

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.

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

OBJECTIVE: To evaluate aortic diameter and predictors of aortic dilatation using 18FDG-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.

Interleukin-6 and soluble interleukin-6 receptor are elevated in large-vessel vasculitis: a cross-sectional and longitudinal study.

OBJECTIVES: To investigate serum levels of IL- 6 and soluble IL-6 receptor (sIL-6R) in patients with large-vessel vasculitis and their relationship with disease activity. METHODS: Sera were obtained from 33 Takayasu's arteritis (TAK) patients and 14 giant cell arteritis (GCA) patients, and from 60 age-matched normal controls (NCs). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Among TAK patients with active disease at baseline, clinical records and serum samples from 11 TAK patients were available for the longitudinal study. IL-6 and sIL-6R serum levels were evaluated using commercial ELISA kits. RESULTS: IL-6 and sIL-6R serum levels were significantly higher in both GCA and TAK patients compared to NCs. IL-6 levels in TAK patients were significantly increased irrespective of disease phase, while a significant increase in sIL-6R concentrations was only found in TAK patients with active disease. Conversely, in GCA, IL-6 levels were significantly raised only in patients with active diseases, whereas sIL-6R levels appeared to be significantly higher irrespective of disease activity. Longitudinal analysis showed that levels of sIL-6R in TAK patients were significantly higher only at baseline, compared to NCs, whereas IL-6 levels were found to be significantly increased at each follow-up time point. CONCLUSIONS: These overall results might suggest a role for sIL-6R as a potential biomarker for disease activity in TAK patients, whereas in GCA, modifications of IL-6 might better identify patients with active disease.

68Ga-DOTATOC PET/CT Imaging in Solitary Fibrous Tumor of the Pleura.

Here we describe a 77-year-old man with a solitary fibrous tumor of the pleura showing increasing tracer uptake at Ga-DOTATOC PET/CT, demonstrating that solitary fibrous tumor of the pleura may overexpress somatostatin receptors, therefore mimicking neuroendocrine tumors at somatostatin receptor PET/CT.

The role of imaging in the diagnosis of recurrence of primary seminal vesicle adenocarcinoma.

Primary seminal vesicle (SV) adenocarcinoma is a rare tumor. A small amount of data about the role of imaging to detect tumor recurrence is available. We report the case of a 58-year-old patient with primary SV clear-cell well-differentiated adenocarcinoma. Clinical and instrumental examinations were negative for the 32 months after treatments when computed tomography scan, [(18)F]fluoro-D-glucose positron emission tomography/computed tomography and pelvic magnetic resonance imaging showed the appearance of a lesion in the left perineal muscle suspected for recurrence. Patient was symptomless. Cytology of the suspected lesion confirmed SV adenocarcinoma recurrence. The combined approach, using radiological and nuclear medicine techniques, seems to be effective in the follow-up of SV adenocarcinoma. Technological advances, together with awareness of this rare tumor, have the potential of improving patients outcomes not only by providing earlier detection and accurate staging, but also by detecting recurrence and thereby avoiding delays and therapeutic dilemmas.

PET and PET/CT with 68gallium-labeled somatostatin analogues in Non GEP-NETs Tumors.

Somatostatin (SST) is a 28-amino-acid cyclic neuropeptide mainly secreted by neurons and endocrine cells. A major interest for SST receptors (SSTR) as target for in vivo diagnostic and therapeutic purposes was born since a series of stable synthetic SST-analouges PET became available, being the native somatostatin non feasible for clinical use due to the very low metabolic stability. The rationale for the employment of SST-analogues to image cancer is both based on the expression of SSTR by tumor and on the high affinity of these compounds for SSTR. The primary indication of SST-analogues imaging is for neuroendocrine tumors (NETs), which usually express a high density of SSTR, so they can be effectively targeted and visualized with radiolabeled SST-analogues in vivo. Particularly, SST-analogues imaging has been widely employed in gastroenteropancreatic (GEP) NETs. Nevertheless, a variety of tumors other than NETs expresses SSTR thus SST-analogues imaging can also be used in these tumors, particularly if treatment with radiolabeled therapeutic SST-analouges PET is being considered. The aim of this paper is to provide a concise overview of the role of positron emission tomography/computed tomography (PET/CT) with (68)Ga-radiolabeled SST-analouges PET in tumors other than GEP-NETs.

Correlation of microvascular fractal dimension with positron emission tomography [(11)C]-methionine uptake in glioblastoma multiforme: preliminary findings.

Neuroradiological and metabolic imaging is a fundamental diagnostic procedure in the assessment of patients with primary and metastatic brain tumors. The correlation between objective parameters capable of quantifying the neoplastic angioarchitecture and imaging data may improve our understanding of the underlying physiopathology and make it possible to evaluate treatment efficacy in brain tumors. Only a few studies have so far correlated the quantitative parameters measuring the neovascularity of brain tumors with the metabolic profiles measured by means of amino acid uptake in positron emission tomography (PET) scans. Fractal geometry offers new mathematical tools for the description and quantification of complex anatomical systems, including microvascularity. In this study, we evaluated the microvascular network complexity of six cases of human glioblastoma multiforme quantifying the surface fractal dimension on CD34 immunostained specimens. The microvascular fractal dimension was estimated by applying the box-counting algorithm. As the fractal dimension depends on the density, size and shape of the vessels, and their distribution pattern, we defined it as an index of the whole complexity of microvascular architecture and compared it with the uptake of (11)C-methionine (MET) assessed by PET. The different fractal dimension values observed showed that the same histological category of brain tumor had different microvascular network architectures. Fractal dimension ranged between 1.19 and 1.77 (mean: 1.415+/-0.225), and the uptake of (11)C-methionine ranged between 1.30 and 5.30. A statistically significant direct correlation between the microvascular fractal dimension and the uptake of (11)C-methionine (p=0.02) was found. Our preliminary findings indicate that that vascularity (estimated on the histologic specimens by means of the fractal dimension) and (11)C-methionine uptake (assessed by PET) closely correlate in glioblastoma multiforme and that microvascular fractal dimension can be a useful parameter to objectively describe and quantify the geometrical complexity of the microangioarchitecture in glioblastoma multiforme.

Whole-body biodistribution and radiation dosimetry of the new cardiac tracer 99mTc-N-DBODC.

UNLABELLED: Our purpose was to evaluate the safety profile and biodistribution behavior in healthy human volunteers of the new myocardial perfusion tracer bis[(dimethoxypropylphosphanyl)ethyl]ethoxyethylamine N,N'-bis(ethoxyethyl)dithiocarbamato nitrido technetium(V) (99mTc-N-DBODC). METHODS: Ten healthy male volunteers were injected with 99mTc-N-DBODC under both stress and rest conditions. Anterior and posterior planar gamma-camera images were collected at 5, 30, 60, 240, and 1,440 min after injection, with organ uptake quantified by region-of-interest analysis. Tracer kinetics in body fluids were determined by collecting blood and urine samples at different time points. RESULTS: After injection, 99mTc-N-DBODC showed significant accumulation in the myocardium and prolonged retention. Under rest conditions, uptake in the heart, lungs, and liver at 5 min after injection was 1.67% +/- 0.13%, 1.16% +/- 0.07%, and 10.85% +/- 1.72%, respectively, of administered activity. Under stress conditions, heart uptake was significantly higher (2.07% +/- 0.22%). Radioactivity in the liver decreased to 3.64% +/- 0.98% and 2.37% +/- 0.48% at 60 and 240 min, respectively, after injection. This rapid liver clearance led to favorable heart-to-liver ratios, reaching values of 0.74 +/- 0.13 at rest and 1.26 +/- 0.28 during exercise 60 min after tracer administration. Radiation dose estimates were comparable to those obtained with other myocardial perfusion cationic compounds. CONCLUSION: The high uptake in the myocardium and the fast liver washout of 99mTc-N-DBODC will allow SPECT images of the left ventricle to be acquired early and with excellent quality.