Luca Indovina

Determining the appropriate time of execution of an I-131 post-therapy whole-body scan: comparison between early and late imaging.

ObjectiveThe aim of this study was to investigate the appropriate time for performing an iodine-131 post-therapy whole-body scan (TxWBS) through a qualitative and semiquantitative analysis of early and late scans. Materials and methodsThis study evaluated pairs of scans of 134 patients who underwent TxWBS on the third and seventh day. The scans were analyzed to evaluate sites, intensity of uptake, concordance or discordance between the scans, relationship with risk factors, and serum thyroglobulin (Tg) levels. To evaluate early and late radioiodine kinetics in thyroid remnants and metastases, 65/134 pairs of scans (48.5%) were subjected to a semiquantitative analysis. ResultsThe early and late scans furnished concordant images in 108/134 patients (80.5%). In 10/134 patients (7.5%), early scans provided more information compared with late scans, showing lymph node and distant metastases in seven and three patients, respectively. In 16/134 patients (12%), late scans provided more data compared with early scans, with thyroid remnants and lymph node and distant metastases demonstrated in four, seven, and five patients, respectively. Negative early/positive late TxWBS results in patients were found to be significantly correlated (P=0.007) with elevated serum levels of Tg and a high-risk for recurrence (P=0.003). ConclusionThis study suggests that in about 20% of patients early or late TxWBS can miss the visualization of thyroid remnants or lymph node or distant metastases, which can be achieved performing both studies. High-risk patients with elevated serum Tg levels should be considered for a late TxWBS, which can demonstrate a possible metastatic involvement that was not diagnosed or that was downstaged by early TxWBS.

Targeted α-Particle Therapy: A Clinical Overview

Among radionuclides usable for tumor therapy, α-particle emitters are characterized by a very high linear energy transfer (LET) resulting in a larger number of ionizations in a range corresponding to a cell diameter. Therefore, they can determine a stronger therapeutic effect compared to low LET β-particle emitters, producing their ionizations in a range up to many millimeters. In fact, because the distance between the two strands of DNA is almost the same as the distance between two ionizations of α-particles, DNA double strand breaks are induced with a high probability that finally cause cell death due to inefficient repair. Conversely, no therapeutic effect can be determined outside of concentrating sites. Therefore, the short range of α-emitters makes them powerful tools mainly when a therapeutic effect has to be reached in a restricted area, as in the elimination of minimal residual disease or in micro-metastases. Therapeutic efficacy of α-emitter radionuclides has been proven in numerous pre-clinical studies, but up to today only three main human studies are reported, including the treatment of myeloid leukemia by an anti-CD33 monoclonal antibody labelled by bismuth- 213 (213Bi), the therapy of patients with bone metastases from hormone-refractory prostate cancer by radium-223 (223Ra) and the loco-regional targeted radiotherapy with astatine-211(211At)-labelled anti-tenascin monoclonal antibody in patients with recurrent malignant brain tumours. The authors reviewed these human reported studies, evaluating perspectives, advantages and limitations of the targeted α-particle therapy.

Diagnostic Performance of 18F-Fluorodeoxyglucose in 162 Small Pulmonary Nodules Incidentally Detected in Subjects Without a History of Malignancy

BACKGROUND Solitary pulmonary nodule (SPN) still represents a diagnostic challenge. The aim of our study was to evaluate the diagnostic performance of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography in one of the largest samples of small SPNs, incidentally detected in subjects without a history of malignancy (nonscreening population) and undetermined at computed tomography. METHODS One-hundred and sixty-two small (>0.8 to 1.5 cm) and, for comparison, 206 large nodules (>1.5 to 3 cm) were retrospectively evaluated. Diagnostic performance of (18)F-fluorodeoxyglucose visual analysis, receiver-operating characteristic (ROC) analysis for maximum standardized uptake value (SUVmax), and Bayesian analysis were assessed using histology or radiological follow-up as a golden standard. RESULTS In 162 small nodules, (18)F-fluorodeoxyglucose visual and ROC analyses (SUVmax = 1.3) provided 72.6% and 77.4% sensitivity and 88.0% and 82.0% specificity, respectively. The prevalence of malignancy was 38%; Bayesian analysis provided 78.8% positive and 16.0% negative posttest probabilities of malignancy. In 206 large nodules (18)F-fluorodeoxyglucose visual and ROC analyses (SUVmax = 1.9) provided 89.5% and 85.1% sensitivity and 70.8% and 79.2% specificity, respectively. The prevalence of malignancy was 65%; Bayesian analysis provided 85.0% positive and 21.6% negative posttest probabilities of malignancy. In both groups, malignant nodules had a significant higher SUVmax (p < 0.0001) than benign nodules. Only in the small group, malignant nodules were significantly larger (p = 0.0054) than benign ones. CONCLUSIONS (18)F-fluorodeoxyglucose can be clinically relevant to rule in and rule out malignancy in undetermined small SPNs, incidentally detected in nonscreening population with intermediate pretest probability of malignancy, as well as in larger ones. Visual analysis can be considered an optimal diagnostic criterion, adequately detecting a wide range of malignant nodules with different metabolic activity.

Feasibility of beta-particle radioguided surgery for a variety of “nuclear medicine” radionuclides

PURPOSE Beta-particle radioguided tumor resection may potentially overcome the limitations of conventional gamma-ray guided surgery by eliminating, or at least minimizing, the confounding effect of counts contributed by activity in adjacent normal tissues. The current study evaluates the clinical feasibility of this approach for a variety of radionuclides. Nowadays, the only β- radioisotope suited to radioguided surgery is 90Y. Here, we study the β- probe prototype capability to different radionuclides chosen among those used in nuclear medicine. METHODS The counting efficiency of our probe prototype was evaluated for sources of electrons and photons of different energies. Such measurements were used to benchmark the Monte Carlo (MC) simulation of the probe behavior, especially the parameters related to the simulation of the optical photon propagation in the scintillation crystal. Then, the MC simulation was used to derive the signal and the background we would measure from a small tumor embedded in the patient body if one of the selected radionuclides is used. RESULTS Based on the criterion of detectability of a 0.1 ml tumor for a counting interval of 1 s and an administered activity of 3 MBq/kg, the current probe yields a detectable signal over a wide range of Standard Uptake Values (SUVs) and tumor-to-non-tumor activity-concentration ratios (TNRs) for 31Si, 32P, 97Zr, and 188Re. Although efficient counting of 83Br, 133I, and 153Sm proved somewhat more problematic, the foregoing criterion can be satisfied for these isotopes as well for sufficiently high SUVs and TNRs.

The Accessory Spleen Is an Important Pitfall of 68Ga-DOTANOC PET/CT in the Workup for Pancreatic Neuroendocrine Neoplasm

Objective The aim of the study was to assess the value and potential pitfalls of 68Ga-DOTANOC positron emission tomography/computed tomography (PET/CT) in patients with suspected pancreatic neuroendocrine neoplasms (pNEN). Methods Consecutive patients referred for 68Ga-DOTANOC PET/CT for suspected pNEN between May 1, 2011, and October 31, 2014, were retrospectively assessed. Scan data were compared with cytological/histological final diagnosis. Pancreatic neuroendocrine neoplasm detection rate was determined on per-patient and per-lesion basis. Maximum standardized uptake values of lesions were determined. Results Fifty-eight patients with 65 lesions were enrolled. Twelve patients had nonconfirmed diagnosis; of these, 7 were positive and 5 negative at PET/CT. Of 46 patients with confirmed diagnosis, 36 had pNEN; of these, 33 were positive, 1 negative, and 2 nonevaluable at PET/CT. Ten patients had non-NE lesions, of which 8 were positive, 1 negative, and 1 nonevaluable at PET/CT. Of 48 patients with positive PET/CT, 8 proved to have non-NE lesions, of which 6 were intrapancreatic accessory spleen. No significant maximum standardized uptake values difference was found between pNEN and non-NE lesions. Conclusions Intrapancreatic accessory spleen is an important pitfall in 68Ga-DOTANOC PET/CT for suspected pNEN. Cytological/histological confirmation is mandatory before any surgical procedure is undertaken.

Measurement uncertainty and clinical impact of target-to-background ratios derived by interim FDG-PET/CT in Hodgkin lymphoma: reply to Laffon and Martan

Dear Sir, Interim FDG-PET/CT imaging performed after the first two cycles of chemotherapy and visually evaluated by Deauville criteria (DS) has proved to be the best prognostic tool in patients with Hodgkin Lymphoma (HL) [1]. Nevertheless, recent studies indicate that DS has some limitations in correctly identifying patients within groups with different prognoses, as false positive and false negative results can be found [1, 2]. So, semi-quantitative parameters, including lesion-tobackground SUV ratios, have been recently proposed to evaluate residual activity in interim FDG-PET/CT [1–4]. In their letter, Laffon and Marthan [5] remarked on some aspects of two different lesion-to-background SUV ratios: qPET by Hasenclever et al. [3] (defined as the ratio between target lesion SUVmean of the four hottest voxels and liver SUVmean in a well defined volume); and rPET by Annunziata et al. [4] (defined as the ratio of target lesion SUVmax to liver SUVmax). Both ratios could have technical advantages over visual analysis with DS, including the intraexam normalization of SUV sources of error and the conversion of a visual qualitative scale in a continuous semiquantitative scale. At the same time, ratios could have clinical advantages over DS related to the use of well-determined cutpoints, subsequent diagnostic standardization and added prognostic power [3–5]. Nevertheless, Laffon and Marthan [5] found an Boriginal sin^ in the use of both ratios in terms of measurement uncertainty (MU), which is calculated as an amplification of single SUV MU and is mathematically higher in ratios with respect to a single SUV measurement. According to their previous works [5], MU of rPET could be evaluated in a dynamic scan as the Brelative difference between a single estimate of a parameter and its average true value^. In our previous study [4], we retrospectively evaluated static PET/CT scans acquired at approximately sixty minutes after FDG injection by collecting a single SUVmax measurement for each target lesion and the liver right lobe. For this reason, MU cannot be evaluated in our study by the method by Laffon andMarthan.We are aware that every kind of measurement is affected by a sort of MU, and ratios have their own MU. On the other hand, the clinical advantages of ratios probably exceed theoretical MU associated to these measurements, from a practical point of view. Concerning this, Laffon and Marthan suggested that metabolic tumor volume (MTV) could improve the target-tobackground approach [5], since it is a Btrue quantitative parameter .̂ However, this is questionable. In fact, MTV is defined as the volume of a tumor with a higher SUV than an established threshold [1, 2]. As well as absolute SUV values, MTVis dependent upon a number of factors, such as the threshold used, the type of volume selection and, again, upon MU. In conclusion, lesion-to-background SUV ratios can improve visual evaluation of interim FDG-PET/CT in patients with HL, in terms of both diagnostic standardization and added prognostic power. We are in accord with Laffon and Marthan [5], that to overcome the possibleMU related to these measurements, further prospective studies with dynamic acquisitions are desirable to collect several SUV measurements at different time points following FDG injection. * Salvatore Annunziata salvatoreannunziata@live.it

Radioprotezione del paziente e della popolazione nella terapia con radioiodio del carcinoma differenziato della tiroide

SommarioIl trattamento con radioiodio del carcinoma differenziato della tiroide è una modalità di cura sostanzialmente sicura e priva di rischi per il paziente e per la popolazione. Risulta tale, se si procede a un’attenta ottimizzazione dell’attività di radioiodio da somministrare e se il paziente viene preparato in maniera accurata e scrupolosa. La radioprotezione dei familiari e della popolazione avviene attraverso il ricorso al trattamento in regime di ricovero protetto e con il rispetto delle informazioni e istruzioni scritte di comportamento rilasciate all’atto della dimissione. Un recente documento congiunto dell’Associazione Italiana di Medicina Nucleare (AIMN) e dell’Associazione Italiana di Fisica Medica (AIFM) riporta le raccomandazioni ufficiali sui criteri di dimissione del paziente dalla degenza protetta e sulle informazioni da fornire ai pazienti, prima, durante e dopo il trattamento. Nell’articolo vengono esaminati i principali aspetti di radioprotezione e i motivi che giustificano le norme di comportamento. È auspicabile che il recepimento della Direttiva 2013/59/Euratom semplifichi e migliori alcuni aspetti della normativa attualmente vigente in materia.

Cerebral metabolic rate for glucose of NPH patients increases in shunt-reponders

Normal pressure hydrocephalus (NPH) is a potentially treatable form of dementia characterised by a triad of symptoms (dementia, gait disturbance and urinary incontinence). This triad is not pathognomic and may also be seen in other degenerative brain diseases (DBD). Diagnosis of NPH is based upon the clinical history/physical examination, brain imaging and CSF dynamics evaluation.1 The regional cerebral metabolic rate for glucose (rCMRglu) has been extensively measured in DBD. However, few PET studies describe a heterogeneous pattern of metabolic alterations in NPH and there is no conclusive evidence at present of an increase in metabolism after insertion of a CSF shunt.2 3 This is a preliminary study reporting changes in PET rCMRglu in patients with NPH …