Federico Caobelli

Role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography for therapy evaluation of patients with large-vessel vasculitis

PurposeSystemic vasculitis is a multisystem disease characterized by inflammation of blood vessels. Diagnosing extension of the disease and evaluating the response to therapy are cornerstones in the clinical management of vasculitis, and imaging has a pivotal role in this field.Materials and methodsWe have evaluated nine patients with large-vessel vasculitis by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) before and after treatment with corticosteroid.ResultsThe evaluation of eight patients was negative at follow-up studies after therapy, and one was unchanged.Conclusions18F-FDG-PET/CT is a useful, accurate tool for establishing the diagnosis of large-vessel vasculitis and for evaluating disease extension in these patients. Despite the small number of patients enrolled, our study confirms this statement and offers preliminary evidence that it could also be a reliable, accurate tool for monitoring therapy in conjunction with clinical and biochemical findings.

The Role of Neuroimaging in Evaluating Patients Affected by Creutzfeldt–Jakob Disease: A Systematic Review of the Literature

Diagnosis of Creutzfeldt–Jakob disease during life can be challenging since the huge variability of the symptoms which can be observed, especially in its early stages, may simulate other common forms of dementia. In latest years, noninvasive techniques such as magnetic resonance, positron emission tomography, and single‐photon emission tomography have been evaluated to help clinical neurologists to provide a definite diagnosis.

124I-MIBG: a new promising positron-emitting radiopharmaceutical for the evaluation of neuroblastoma

Neuroblastoma is the most common extra-cranial solid tumor in pediatric patients. Despite the established role of 123I-MIBG and 131I-MIBG scintigraphy in this tumor, only limited data are available regarding the use of 124I-metaiodobenzylguanidine (MIBG) positron emission tomography (PET)/computed tomography (CT). We present our preliminary experience with 124I-MIBG PET/CT: two pediatric patients affected by neuroblastoma, who underwent 124I-MIBG PET/CT for pre-therapy distribution evaluation and restaging purposes. We aimed to evaluate whether 124I-MIBG PET/CT can detect as many or more neuroblastoma lesions than 123I/131I-MIBG imaging. Our cases show promising results, although further validation and standardization of 124I-MIBG PET/CT are required.

FOXP2, APOE and PRNP new modulators in primary progressive aphasia

Primary progressive aphasia (PPA) is a heterogeneous disorder characterized by progressive language impairment. Polymorphisms within forkhead box P2 gene (FOXP2) gene have been associated with speech and language impairment. Apolipoprotein E (APOE) genotype and PRNP 129 codon status have been demonstrated to increase the risk of PPA, but with contrasting results. In the present study, we have evaluated the impact of FOXP2, APOE and PRNP genetic variations as risk factors and/or disease-modulators in PPA. 94 PPA patients and 200 age-matched healthy controls were considered and FOXP2 polymorphisms (rs1456031, rs17137124), APOE genotype, and PRNP codon 129 polymorphism analyzed. In 34 PPA patients, SPECT imaging data were analyzed by Statistical Parametric Mapping (SPM8). Genetic distributions and allele frequencies of FOXP2 and PRNP polymorphisms did not differ between groups while APOE ε4 was more represented in PPA as compared to controls. PPA patients carrying at-risk FOXP2 polymorphisms (rs1456031 and/or rs17137124) showed greater hypoperfusion in the frontal areas, namely the left inferior frontal gyrus and the right cingulated gyrus compared to non-carriers (p < 0.005). PPA patients carrying at least one ε4 allele had greater hypoperfusion in orbitofrontal regions (superior frontal gyrus and orbital gyrus) as compared to non-carriers ε4 (p < 0.005). PRNP codon 129 homozigosity correlated with left frontotemporal hypoperfusion (p < 0.005). Genetic variations within FOXP2, APOE, and PRNP modulate PPA disease, leading to a specific regional hypoperfusion according to different molecular pathways. APOE ε4 is overrepresented in PPA, thus likely acting as genetic risk factor on disease development.

Uncommon 18F-FDG-PET/CT findings in patients affected by limbic encephalitis: hyper-hypometabolic pattern with double antibody positivity and migrating foci of hypermetabolism☆ , ☆☆

Autoimmune limbic encephalitis (LE) is a rare disorder; its diagnosis can be challenging. We report two uncommon cases of LE evaluated by brain 2-deoxy-2-[18F]fluoro-d-glucose ((18)F-FDG) positron emission tomography/computed tomography describing the metabolic imaging patterns, which were different from those observed in previous studies: the first one presented an unprecedented (18)F-FDG brain mixed pattern, involving also the midbrain, despite negative magnetic resonance imaging exams; the second one showed migrating foci of hypermetabolism, one of which turned into hypometabolism at a later examination.

An Unusual Muscular Metastasis in a Patient Affected by Ileal Carcinoid Imaged With a 111In-Pentetreotide SPECT/CT Scan and Confirmed by Biopsy

¹¹¹In-Pentetreotide SPECT/CT scan has been widely validated in diagnosis and follow-up of carcinoid and other neuroendocrine tumors. A 70-year-old man, who underwent an ileal resection for carcinoid 5 years ago, came to our observation during follow-up. We performed a In-DTPA-Pentetreotide (150 MBq) SPECT/CT scan. Images taken after 2 hours showed a focal, pathologic uptake on the left leg, confirmed at later acquisitions. Lateral projection showed that the uptake area was located in a leg muscle; the lesion was confirmed as an intramuscular metastasis by biopsy. Intramuscular metastasis of carcinoid tumors is an extremely rare manifestation, particularly if not adjacent to the primary tumor, because the muscle is a very uncommon location of hematogenous metastases.

Proposal for an optimized protocol for intravenous administration of insulin in diabetic patients undergoing 18f-fdg Pet/ct

The objective of this study was to evaluate the usefulness and impact of insulin administration before an 18F-FDG PET/computed tomography (CT) examination in diabetic patients in order to propose an optimized protocol that can reduce blood glucose levels without increasing muscular 18F-FDG uptake. A total of 130 patients underwent an 18F-FDG PET/CT. Twenty patients had glucose levels greater than 180 mg/dl and received endovenous insulin before 18F-FDG injection (group 1); 10 patients had glucose levels greater than 160 mg/dl and lower than 200 mg/dl and received no insulin (group 2); 100 patients were euglycemic (group 3). Biodistribution was adequate in 19 of 20 patients in group 1. Values of standardized uptake value in the gluteal muscle were 0.50±0.18 for group 1, 0.48±0.10 for group 2, and 0.49±0.08 for group 3; no significant differences in muscular 18F-FDG uptake could be found among the three groups. No adverse events were recorded. In conclusion, our protocol has been demonstrated to be safe and effective, with only a minor impact on glucose biodistribution and apparently without affecting PET accuracy.

Extraosseous myocardial uptake incidentally detected during bone scan: report of three cases and a systematic literature review of extraosseous uptake

Bone scintigraphy is widely considered as an important technique able to investigate various pathological conditions of the skeletal system. Many unexpected extraosseous uptakes have been reported in literature. We present here three cases of unexpected 99mTc-oxidronate (HDP) myocardial extraosseous uptakes in patients undergoing bone scan for staging purposes. In particular, we present the first reported case ofa myocardial uptake in a patient with IgM-related amyloidosis. Subsequently, we perform a review of the existing literature about extraosseous uptakes.

Prognostic significance of FDG PET/CT on the follow-up of patients of differentiated thyroid carcinoma with negative I131 whole-body scan and elevated thyroglobulin levels.

To the Editor: Avery interesting article has been recently published on Clinical Nuclear Medicine about the prognostic significance of FDG PET/CT on the follow-up of patients with differentiated thyroid carcinoma with negative 131I scan and elevated thyroglobulin (Tg) levels. The authors evaluated 105 patients with negative I whole-body scan with high Tg levels; all patients underwent F-FDG PET/CT, and the results were also analyzed in comparison to Tg levels. PET/CT was positive in 75 patients (69 true-positive and 6 false-positive results) and negative in 30 (20 true-negative and 10 false-negative results), thus reaching 87% sensitivity, 77% specificity, 92% positive predictive value, 66% negative predictive value, and 75% accuracy. The authors also reported that PET/CT accuracy dramatically increase when Tg levels are greater than 38.2 ng/mL with thyroid-stimulating hormone (TSH) stimulation greater than 1.9 ng/mL under TSH suppression, thus reaching 93%. One of the most interesting findings is the fact that patients with a negative F-FDG PET/CT examination and Tg values that can be ‘‘suppressed’’ by hormone therapy are reported to have a more favorable prognosis regarding mortality and risk of recurrence, and this aspect seems to be unrelated to Tg levels in ‘‘off-therapy.’’ Although the importance of Tg values for prognosis has been extensively evaluated, this appears to be the first time that this aspect is demonstrated to have a prognostic significance for recurrent thyroid carcinoma. This could underline another important mechanism in dedifferentiation, which could be a part of a more complex series of molecular changes involved in the loss of capability of I uptake. Up to now, several mechanisms have been discovered in the dedifferentiation process. The so-called flip-flop phenomenon, defined as the inverse relationship between 131I and 18F-FDG uptake in thyroid carcinoma, due to high GLUT-1 (glucose transporter type 1) gene expression associated with a decrease in energy-dependent transport mediated by the Na/I-symporter, has been recently hypothesized to be also related to PTEN (phosphatase and tensin homolog) expression, which might affect the surface expression of GLUT-1. Besides this well-known phenomenon, a second metabolic change has been suspected by another recent study by RosenbaumKrumme et al, corroborated by the fact that also thyroid incidentalomas, which are for the most part benign lesions or carcinomas in a very early stage, often show high FDG uptake. Now, this article seems to demonstrate that the modifications in the mechanisms of feedback of Tg secretion could be another important parameter in the process of dedifferentiation; in fact, patients whose Tg secretion is not inhibited by hormone therapy have a worse prognosis, strictly related with a higher grade of dedifferentiation. Many molecular chaperones and folding enzymes, such as BiP, GRP94, calnexin, protein disulfide isomerase, endoplasmic reticulum protein 72 (ERp72), and more recently ERp29, have been shown to associate simultaneously and/or sequentially with Tg in the course of its maturation, thus forming large heterocomplexes in the endothelium reticulum of thyrocytes. Anyway, their role also in modifying Tg secretion and their interrelation with other factors is still under active investigation. In particular, ERp29 has been recently studied in the Tg secretion as well as in carcinogenesis, and there is an evidence of high ERp29 levels in tumors of various origins and under the conditions of genotoxic stress, such as ionizing radiation; moreover, there is the evidence p53 is strictly correlated on the effect of antineoplastic drugs on ERp29, thus suggesting that a modification in p53, as it often happens during dedifferentiation, can affect in many ways Tg secretion and feedback. More recently, also ghrelin, a 28-aminoacid peptide mainly secreted by the stomach and that both stimulates pituitary growth hormone secretion and modulates food intake and energy metabolism in mammals, has been demonstrated to have a stimulatory effect on TSH-induced expression of the tissue-specific key genes involved in the synthesis of Tg. Taken together with the findings of Vural et al, these data suggest that understanding the physiopathologic mechanisms and metabolic ways of determining differences in radiopharmaceutical uptake and correlating these findings with microscopic and clinical patterns are indispensable to precisely clarify the real meaning of FDG hypermetabolism or hypometabolism and its prognostic value, the possible use of Tg values for prognostic purposes, and possible targets for an adequate and satisfactory therapy.

Reversible striatal hypermetabolism in a case of rare adult-onset Sydenham chorea on two sequential 18F-FDG PET studies

Journal of Neuroradiology - In Press.Proof corrected by the author Available online since jeudi 6 janvier 2011