Giovanella L, Castellani M, Suriano S, Ruberto T, Ceriani L, Tagliabue L, Lucignani G.
Tumori. 2011 Sep-Oct;97(5):629-33.'
Aim. The aim of this study was to compare the diagnostic performance of whole-body bone scintigraphy (WBS) and multi-field-of-view single photon emission tomography (multi-FOV SPECT) with 99mTc-oxidronate (99mTc-HDP) in patients with prostate cancer (Pca). Methods. In a prospective study, WBS and SPECT acquisitions were performed in 194 patients with histologically confirmed Pca and serum prostate-specific antigen (PSA) levels above 10 ng/mL. Scans obtained using the two modalities were interpreted separately. Clinical and biochemical follow-up, radiological studies and biopsies served as benchmarks for the assessments. The impact of PSA level on WBS and SPECT results was also evaluated. Results. The patient-based sensitivity, specificity, accuracy, PPV and NPV values of SPECT examinations were higher than those of WBS, especially in patients with serum PSA levels <40 ng/mL. Conclusion. Multi-FOV SPECT proved to be more sensitive and specific than WBS in detecting bone metastases in Pca patients.
Martelli C, Borelli M, Ottobrini L, Rainone V, Degrassi A, Russo M, Gianelli U, Bosari S, Fiorini C, Trabattoni D, Clerici M, Lucignani G.
Mol Imaging Biol. 2012 Apr;14(2):183-96.'
PURPOSE: The authors present a protocol for the in vivo evaluation, using
different imaging techniques, of lymph node (LN) homing of tumor-specific
dendritic cells (DCs) in a murine breast cancer model. PROCEDURES: Bone marrow
DCs were labeled with paramagnetic nanoparticles (MNPs) or (111)In-oxine. Antigen loading was performed using tumor lysate. Mature DCs were injected into the footpads of transgenic tumor-bearing mice (MMTV-Ras) and DC migration was tracked by magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). Ex vivo analyses were performed to validate the imaging data. RESULTS: DC labeling, both with MNPs and with (111)In-oxine, did not affect DC phenotype or functionality. MRI and SPECT allowed the detection of iron and (111)In in both axillary and popliteal LNs. Immunohistochemistry and γ-counting revealed the presence of DCs in LNs. CONCLUSIONS: MRI and SPECT imaging, by allowing in vivo dynamic monitoring of DC migration, could further the development and optimization of efficient anti-cancer vaccines.
Libani IV, Lucignani G, Gianelli U, Degrassi A, Russo M, Bosari S, Clerici M, Ottobrini L.
Mol Imaging Biol. 2012 Feb;14(1):47-59.'
PURPOSE: We propose herein labeling protocols for multimodal in vivo visualization of human skeletal muscle cells (HSkMCs) by MRI and BLI to investigate the survival, localization, and proliferation/differentiation of these cells in cell-mediated therapy. PROCEDURES: HSkMCs were labeled with different quantities of Endorem® and transfection agents or infected with lentiviral vector expressing the luciferase gene under the myogenin promoter. Cells were evaluated before and after intra-arterial injection in NUDE mice with N(2)-induced muscle inflammation. RESULTS: Neither iron labeling nor infection affected cell features; the number of iron-positive cells increased proportionally to the iron content in the medium and in the presence of transfection agents. Loaded cells were detected for up to 1 month by MRI and 2 months by BLI. CONCLUSIONS: These protocols could be used to visualize new stem cells, in vivo and over time, in preclinical studies of cell-based treatments for myopathies of different etiologies.
Ottobrini L, Martelli C, Trabattoni DL, Clerici M, Lucignani G.
Eur J Nucl Med Mol Imaging. 2011 May;38(5):949-68.'
Tumour establishment, progression and regression can be studied in vivo using an array of imaging techniques ranging from MRI to nuclear-based and optical techniques that highlight the intrinsic behaviour of different cell populations in the physiological context. Clinical in vivo imaging techniques and preclinical specific approaches have been used to study, both at the macroscopic and microscopic level, tumour cells, their proliferation, metastasisation, death and interaction with the environment and with the immune system. Fluorescent, radioactive or paramagnetic markers were used in direct protocols to label the specific cell population and reporter genes were used for genetic, indirect labelling protocols to track the fate of a given cell subpopulation in vivo. Different protocols have been proposed to in vivo study the interaction between immune cells and tumours by different imaging techniques (intravital and whole-body imaging). In particular in this review we report several examples dealing with dendritic cells, T lymphocytes and macrophages specifically labelled for different imaging procedures both for the study of their physiological function and in the context of anti-neoplastic immunotherapies in the attempt to exploit imaging-derived information to improve and optimise anti-neoplastic immune-based treatments.
Del Sole A, Chiesa V, Lucignani G, Vignoli A, Giordano L, Lecchi M, Canevini MP.
Q J Nucl Med Mol Imaging. 2010 Oct;54(5):564-569
.'
AIM: Several lines of evidence indicate that the dopaminergic system may play a role in the propagation of epileptic seizures and, indeed, DOPA metabolism impairment has recently been demonstrated in PET studies of ring chromosome 20 [r(20)] patients. We conducted a study looking for correlations between r(20) mosaicism, other clinical variables and both pre-synaptic dopamine transporter (DAT) expression and post-synaptic D2 receptor density. METHODS: Five patients with r(20) and epilepsy were enrolled in the study. DAT expression and D2 density were measured by single photon emission tomography (SPECT) imaging with 185 MBq of [123I]ioflupane and [123I]IBZM, respectively, on different days. Linear correlations between r(20) mosaicism, clinical variables and binding of [123I]ioflupane or [123I]IBZM were examined. RESULTS: A significant correlation between seizure frequency and r(20) mosaicism was detected (r=0.903, P<0.05), along with a negative correlation between r(20) mosaicism and binding of [123I]ioflupane in the putamen and in the caudate nucleus (r=-0.692 and r=-807; P<0.05). Seizure frequency was positively correlated with post-synaptic D2 density (r=0.925, P<0.05). CONCLUSION: Striatal neurons are involved in r(20) epilepsy; the relationship found between r(20) mosaicism and DAT expression suggests that drugs acting on the dopaminergic system could have a place in the treatment of this rare form of epilepsy.
Lu F, Carlino M, Lu C, Landoni C, Lucignani G, Fragasso G, Bello VD, Margonato
A, Chierchia SL, Marzilli M, Balbarini A.
Echocardiography. 2010 May 1;27(5):544-51.'
Background: The aim of this study was to evaluate enoximone echocardiography (EE) for the identification of residual myocardial viability in postinfarction patients. Findings obtained during EE were compared with those acquired by myocardial uptake of fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and functional follow-up results. Methods: Twenty-five patients underwent EE and PET 18F-FDG studies. An asynergic segment was considered as having contractile enhancement when the wall motion score decreased by ≥1 grade during EE and was defined as viable if 18F-FDG uptake score was ≥2 grade on PET. Results: Of 293 dysfunctional segments at baseline, 139 (47%) were viable by PET criteria; 117 (40%) had contractile enhancement induced by enoximone (P = 0.07). Agreement between EE and PET was found in 75% of involved segments (K = 0.46, P < 0.001). The majority of discrepancies (65%, P < 0.01) were mainly due to discordant segments in which PET revealed evidence of 18F-FDG uptake but EE showed no change in wall motion. In 179 revascularized segments, negative predictive value for functional recovery of both tests reached the same value (89% for both), whereas positive predictive value was 82% for EE and 68% for PET, respectively (P < 0.05). Sensitivity was 85% for EE and 88% for PET (P = ns); specificity was 87% and 70%, respectively (P < 0.01). Conclusions: EE yields a fair concordance with PET study. Compared with PET, despite a similar negative accuracy, EE shows a greater specificity for prediction of function recovery after revascularization. (Echocardiography 2010;27:544-551)
Bombardieri E, Coliva A, Maccauro M, Seregni E, Orunesu E, Chiti A, Lucignani G.
Q J Nucl Med Mol Imaging. 2010 Feb;54 (1):3-15.'
Nuclear medicine can image some tumors by means of receptor specific radiopharmaceuticals, and offers the possibility to characterize cancer through the detection of its receptor expression. This is the case of neuroendocrine tumours (NETs), that are visualized by different radiolabelled somatostatin analogues that bind 5 distinct somatostatin receptor types (named sstr1-5) that show different tissue distribution. The subtypes sstr2 and sstr5 are the most commonly expressed in NETs. Until now the most widely used radiolabelled somatostatin analogue for planar and single photon emission computed tomography (SPECT) has been [111In]pentetreotide, because of its commercial availability. Other analogues labelled with gamma emitting radionuclides are [99mTc]EDDA/HYNIC-TOC, [99mTc]P829, [111In]DOTA-lanreotide, [111In]DOTA-NOC-ATE, [111In]DOTA-BOC-ATE. However, these compounds have not been successful for the routine use. Moreover, NETs express various receptors that can be depicted by different radiopharmaceuticals, such as [123I]VIP and [111In]GLP-1. Besides this, some precursors of the catecholamines metabolism, as meta-iodo-benzyl-guanidine (MIBG), labelled with 123I or 131I, accumulates in neuroendocrine tissues, in particular those of sympathoadrenal lineage. MIBG scintigraphy is currently indicated for neuroblastoma, paraganglioma and phaeocromocitoma. An impressive technological progress has been achieved recently with PET and, in particular, with the development of hybrid instrumentations (PET/CT) combining nuclear imaging with radiological imaging providing both functional and morphologic information. Among positron emitting tracers, the [18F]FDG is the most diffuse in oncology, but other more effective tracers are available for NETs, such as the analogues labelled with 68Ga. The diagnostic sensitivity and accuracy of these technology is superior to that of gamma emitting radiopharmaceuticals, but the fact that they are not still registered limits their use in the clinical practice. This overview summarizes the state of art of NETs imaging, focusing the attention mainly on gamma-emitting tracers.
Giovanella L, Lucignani G.
Eur J Nucl Med Mol Imaging. 2010 May;37(5):973-9.'
Never before has medical practice been as dependent as it is today on the use of biomedical imaging technologies which, by exploiting various forms of energy, make it possible to depict the morphology and function of the human body. The development of these technologies has been driven by the demand for better, noninvasive means of acquiring clinically relevant information. Today, in the most economically privileged countries and social classes at least, the wide availability of biomedical imaging devices is one of the main factors involved in medical decision-making processes. It is, therefore, not surprising that on two occasions the Nobel Prize for Medicine or Physiology has been awarded not to physicians, but to scientists in the hard sciences and technologies (physics, chemistry and engineering), involved in the development of imaging techniques. Thirty years ago it went to the inventors of X-ray computed tomography (CT) and as recently as 6 years ago to the inventors of magnetic resonance imaging (MRI). Indeed, the crucial role of imaging in medicine was quickly recognised and has continued to be appreciated over the years.
Clerici F, Del Sole A, Chiti A, Maggiore L, Lecchi M, Pomati S, Mosconi L, Lucignani G, Mariani C.
Q J Nucl Med Mol Imaging. 2009 Dec;53(6):646-57.'
AIM: The aim of this study was to assess whether 18F-fluorodeoxyglucose positron emission tomography differentiates amnestic (aMCI) from single-non-amnestic mild cognitive impairment (snaMCI) with executive dysfunction. METHODS: Sixteen aMCI subjects (62% females, age 75+/-8 years) and 14 snaMCI subjects (71% females, age 74+/-6 years) underwent [18F]FDG-PET and clinical follow-up. Comparisons between MCI subgroups and with seven cognitively normal elderly subjects were performed using SPM2. RESULTS: At baseline aMCI and snaMCI exhibited a similar pattern of hypometabolism, mostly in the posterior cingulate gyrus, as compared with controls. In the comparison between the MCI subtypes, the aMCI subjects showed reduced metabolism in the medial temporal lobes (MTL) (hippocampus, fusiform gyrus and amygdala). At follow-up 12 aMCI developed Alzheimer's disease (AD), while snaMCI had a heterogeneous course, including five subjects who developed Lewy body dementia. CONCLUSIONS: The patterns of altered brain metabolism in aMCI and snaMCI subjects compared to controls are similar and do not provide evidence for making clinical distinctions between them. Comparison between the two MCI subtypes showed MTL hypometabolism in aMCI subjects, possibly reflecting the fact that most had prodromal AD.
Lucignani G, Orunesu E, Cesari M, Marzo K, Pacei M, Bechi G, Gori A, Gaito S, Clerici M, Chiti A.
Eur J Nucl Med Mol Imaging. 2009 Apr;36(4):640-7. Epub 2008 Dec 11.'
PURPOSE: To characterise tissue sites of immune activation and HIV replication we performed FDG-PET in ART-treated and ART-naive HIV-infected individuals. Specific aims were to establish whether HIV-infected patients can be differentiated on the basis of the detection of specific locations of viral replication, even in the presence of an apparently optimal immunovirological response to ART, and whether these FDG-PET findings can be related to immunovirological variables and AIDS history status. PATIENTS AND METHODS: Patients were divided into five groups as follows: subgroup A1 (full responders, n = 8): current ART treatment, CD4+ T lymphocytes >500/mL, viral load <50 copies/mL; subgroup A2 (full responders, n = 5): same criteria as A-1, but with a previous history of AIDS; subgroup A3 (immunological non responders, n = 5): current ART treatment, viral load <50 copies/mL, low CD4+ T lymphocytes (<200/mL); group B (virological non responders, n = 2): current ART treatment, CD4+ T lymphocytes around 500/mL, viral load >50,000 copies/mL; group C (ART-naïve, n = 5): no current or previous ART treatment, increased viral load. RESULTS: PET images revealed different patterns of FDG uptake. All ART-treated patients with either suppressed (<50 copies/mL; Group A) or high viremia (group B) showed a normal pattern of FDG uptake. On the contrary, the ART-naïve subjects with high viraemia (group C) displayed multiple foci of increased glucose metabolism in the lymph nodes. In the ART-naïve subjects, FDG uptake, apparently related to viraemia level, was observed in the upper torso mainly in the axillary nodes bilaterally in patients with viraemia below 100,000 copies/mL; in those with viraemia higher than 100,000 copies/mL, FDG uptake was also observed in the inguinal lymph nodes. CONCLUSIONS: The emergence, in our study, of a correlation between the percentage of CD8+/CD38+/RO+ T cells (well established markers of progression to AIDS independently of CD4+ T lymphocytes) and positive FDG-PET in ART-naive patients is a novel finding that seems to confer prognostic value on FDG uptake. FDG uptake is strongly associated with response to ART independently of a previous AIDS diagnosis. Notably, no differences were observed between ART-treated subjects classed as immunological responders and those classed as non responders. Data herewith indicate that FDG uptake and immunological variables are unrelated when ART is being administered. This is evidence of the complementarity of immunological and FDG measures. FDG uptake is a sensitive marker of disease state and its relation with CD8+/CD38+/CD45RO+ T cells indicates that it can be considered a marker of disease status. The lack of a correlation between FDG uptake and immunological variables in patients under ART warrants further investigation.
Del Sole A, Clerici F, Chiti A, Lecchi M, Mariani C, Maggiore L, Mosconi L, Lucignani G.
Eur J Nucl Med Mol Imaging. 2008 Jul;35(7):1357-66. Epub 2008 Apr 17.'
PURPOSE: The purpose of the study was the identification of group and individual subject patterns of cerebral glucose metabolism (CMRGlu) in patients with Alzheimer's disease (AD) and with amnestic mild cognitive impairment (aMCI). METHODS: [(18)F]fluorodeoxyglucose positron emission tomography (PET) studies and neuropsychological tests were performed in 16 aMCI patients (ten women, age 75 +/- 8 years) and in 14 AD patients (ten women, age 75 +/- 9 years). Comparisons between patient subgroups and with a control population were performed using Statistical Parametric Mapping. RESULTS: Clusters of low CMRGlu were observed bilaterally in the posterior cingulate cortex (PCC), in the precuneus, in the inferior parietal lobule and middle temporal gyrus of AD patients. In aMCI patients, reduced CMRGlu was found only in PCC. Areas of low CMRGlu in PCC were wider in AD compared to aMCI and extended to the precuneus, while low CMRGlu was found in the lateral parietal cortex in AD but not in aMCI patients. Individual subject pattern analysis revealed that 86% of AD patients had low CMRGlu in the PCC (including the precuneus in 71%), 71% in the temporal cortex, 64% in the parietal cortex and 35% in the frontal cortex. Among the aMCI patients, 56% had low CMRGlu in the PCC, 44% in the temporal cortex, 18% in the frontal cortex and none in the parietal cortex. CONCLUSION: This study demonstrates that both AD and aMCI patients have highly heterogeneous metabolic impairment. This potential of individual metabolic PET imaging in patients with AD and aMCI may allow timely identification of brain damage on individual basis and possibly help planning tailored early interventions.
Mosconi L, Tsui WH, Herholz K, Pupi A, Drzezga A, Lucignani G, Reiman EM, Holthoff V, Kalbe E, Sorbi S, Diehl-Schmid J, Perneczky R, Clerici F, Caselli R, Beuthien-Baumann B, Kurz A, Minoshima S, de Leon MJ.
J Nucl Med. 2008 Mar;49(3):390-8. Epub 2008 Feb 20.'
This multicenter study examined (18)F-FDG PET measures in the differential diagnosis of Alzheimer's disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB) from normal aging and from each other and the relation of disease-specific patterns to mild cognitive impairment (MCI). METHODS: We examined the (18)F-FDG PET scans of 548 subjects, including 110 healthy elderly individuals ("normals" or NLs), 114 MCI, 199 AD, 98 FTD, and 27 DLB patients, collected at 7 participating centers. Individual PET scans were Z scored using automated voxel-based comparison with generation of disease-specific patterns of cortical and hippocampal (18)F-FDG uptake that were then applied to characterize MCI. RESULTS: Standardized disease-specific PET patterns were developed that correctly classified 95% AD, 92% DLB, 94% FTD, and 94% NL. MCI patients showed primarily posterior cingulate cortex and hippocampal hypometabolism (81%), whereas neocortical abnormalities varied according to neuropsychological profiles. An AD PET pattern was observed in 79% MCI with deficits in multiple cognitive domains and 31% amnesic MCI. (18)F-FDG PET heterogeneity in MCI with nonmemory deficits ranged from absent hypometabolism to FTD and DLB PET patterns. CONCLUSION: Standardized automated analysis of (18)F-FDG PET scans may provide an objective and sensitive support to the clinical diagnosis in early dementia.