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Background: In neuroendocrine tumor (NET), complete surgery could better the prognosis. Radioguided surgery (RGS) with β−-radioisotopes is a novel approach focused on developing a new probe that, d...

To investigate the cause of lymphopenia in patients with newly diagnosed COVID-19, we measured [We studied, by [Patients had moderate severity COVID-19 syndrome. Basal [These findings indicate that lymphopenia in COVID-19 patients is associated with large bowel inflammation supporting the hypothesis that CD4 + lymphocytes migrate to peripheral lymphoid tissues in the bowel.

This paper provides a first insight of the potential of the β - Radio Guided Surgery ( β - -RGS) in a complex surgical environment like the abdomen, where multiple sources of background concur to the signal at the tumor site. This case is well reproduced by ex-vivo samples of 90 Y -marked Gastro-Entero-Pancreatic Neuroendocrine Tumors (GEP NET) in the bowel. These specimens indeed include at least three wide independent sources of background associated to three anatomical districts (mesentery, intestine, mucose). The study is based on the analysis of 37 lesions found on 5 samples belonging to 5 different patients. We show that the use of electrons, a short range particle, instead of γ particles, allows to limit counts read on a lesion to the sum of the tumor signal plus the background generated by the sole hosting district. The background on adjacent districts in the same specimen/patient is found to differ up to a factor 4, showing how the specificity and sensitivity of the β - -RGS technique can be fully exploited only upon a correct measurement of the contributing background. This locality has been used to set a site-specific cut-off algorithm to discriminate tumor and healthy tissue with a specificity of 100% and a sensitivity, on this test data sample, close to 100%. Factors influencing the sensitivity are also discussed. One of the specimens set allowed us evaluate the volume of the lesions, thus concluding that the probe was able to detect lesions as small as 0.04 mL in that particular case.

Purpose Radio-guided surgery with β - decays is a novel technique under investigation. One of the main advantages is its capability to detect small ( ⩽ 0.1 ml) samples after injecting the patient with low activity of radiopharmaceutical. This paper presents an experimental method to quantify this feature based on ex-vivo tests on specimens from meningioma patients. Methods Patients were enrolled on the basis of the standard uptake value (SUV) and the tumour-to-non-tumour activity ratio (TNR) resulted from 68Ga-DOTATOC PET exams. After injecting the patients with 93–167 MBq of 90Y-DOTATOC, 26 samples excised during surgery were analyzed with a β - probe. The radioactivity expected on the neoplastic specimens was estimated according to the SUV found in the PET scan and the correlation with the measured counts was studied. The doses to surgeon and medical personnel were also evaluated. Results Even injecting as low as 1.4 MBq/kg of radiotracer, tumour residuals of 0.1 ml can be detected. A negligible dose to the medical personnel was confirmed. Conclusions Radio-guided surgery with β - decays is a feasible technique with a low radiation dose for both personnel and patient, in particular if the patient is injected with the minimum required activity. A correlation greater than 80% was observed between the measured counts and the expected activity for the lesion samples based on the individual SUV and the TNR. This makes identifiable the minimum injectable radiotracer activity for cases where 90Y is the utilized radionuclide.

Objectives Pleomorphic lung carcinoma (PLC) is a rare histotype of non-small cell lung cancer (NSCLC) characterized by aggressive clinical course, poor response to therapy and poor prognosis. Therefore, aim of our study is to analyze with 18F-FDG PET/CT a subset of patients affected by PLC to evaluate their metabolic characteristics in terms of SUVmax, MTV and TLG, in order to correlate them with overall survival (OS) and disease-free survival (DFS). Material and methods We retrospectively analyzed 49 consecutive patients with histologically defined PLC occurred to our Institution between 2003 and 2014. All patients underwent F18-FDG PET-CT before surgery and primary tumor was automatically segmented using an isocontour threshold method. SUV threshold for tumor segmentation was defined as the 41 % of lesion SUVmax. Total volume of the segmented VOI (MTV, centimeters cubed) and average SUV (SUVavg, grams per milliliter) in the segmented VOI were measured. Results In our population men were significantly more affected than women (42:7). According to Youden criteria, SUVmax, MTV41 and TLG41 best cut-off values to predict 2-year mortality were, 18.95, 27.89 and 290.45, respectively, with TLG41 showing best specificity (85 %) and positive predictive value (82.4 %). As concerning 2-year recurrence, SUVmax, MTV41 and TLG41 best cut-off values were 10.08, 27.89 and 134.85, with SUVmax showing best sensitivity (96.7 %) and negative predictive value (85.7 %). ROC curves confirmed that SUVmax, MTV41 and TLG41 were equally accurate to predict 2-year mortality and 2-year recurrence in our population. Conclusion Metabolic biomarkers such as SUVmax, MTV and TLG can be used as a prognostic index for disease progression, recurrence and death in patients with PLC, independently from other clinical/pathological prognostic elements.

Objective The aim of this case series is to describe our experience in diagnosis and management of oncological asymptomatic patients with COVID-19 who underwent 18F-FDG PET/CT. Methods From March 9 to March 31, 2020, we identified 5 patients who had PET/CT findings suspicious for COVID-19, but no symptom of infection. Results The first three patients were administered an SARS-CoV-2 test in a COVID-dedicated center, while the fourth and fifth were tested in our institution, in accordance with a new internal procedure. The SARS-CoV-2 test yielded positive results in all five patients. Conclusion In this COVID-19 emergency, our task as radiologists and nuclear medicine physicians is to be able to identify imaging findings suggestive of the disease and to manage patients without overloading the hospital system.

Excisional biopsy of non-palpable rib tumors still represents a challenge for thoracic surgeons: in fact primary or metastatic tumors originating from a rib can be difficult to localize topographically at the time of excisional biopsy, thus potentially resulting in inappropriately placed skin incisions, incomplete tumor excision or even in wrong rib or segment resection (1).

The radiolabeled choline is a PET/CT radiopharmaceutical useful in detecting tumors with high lipogenesis rate.

Radio-Guided Surgery (RGS) is a surgical technique aimed at assisting the surgeon to reach as complete a resection of the tumoural lesion as possible. Established methods to date make use of \( \gamma \)-emitting tracers to radio-mark the neoplastic tissue. However, in case of uptake from healthy organs around the lesion the large penetration of photons yields a non-negligible background that can limit the RGS application. The adoption of \( \beta^{ - } \) radiation has been proposed to overcome this limit. To validate the entire RGS procedure, from the evaluation of the tracer uptake of the tumor, to the assumptions on the bio-distribution and the signal detection, tests on ex vivo specimens of meningioma brain tumour were performed. Meningioma was selected due to the well known high receptivity to a \( \beta^{ - } \) emitting radio-tracer already in use in the clinical practice: 90Y-labelled DOTATOC. Patients were enrolled according to the tumour Standard Uptake Value (SUV \( > \) 2) and the expected Tumour to Non-tumour Ratio (TNR \( > \) 10) estimated from 68Ga-DOTATOC PET images. After injecting the patients with 93–167 MBq of \( ^{90} Y - DOTATOC \), 26 samples excised during surgery were examined with a dedicated \( \beta^{ - } \) detecting probe to assess the sensitivity of millimetre-sized tumour remnants in case of administration of low activity value compatible with those injected for diagnostic exams. Even injecting as low as 1.4 MBq/kg of radio-tracer, tumour remnants greater than 0.06 ml would be discriminated by the healthy tissue in few seconds.

Purpose To investigate the impact of 68 Ga-DOTATOC PET/CT in addition to MRI and CT for retrospectively assessing the GTV delineation of meningiomas of the skull base in patients treated with particle therapy. Methods Sixteen patients underwent 68 Ga-DOTATOC PET/CT for diagnosis followed by constract-enhanced (CE) MRI and CT for treatment planning with particle therapy.GTV was defined on the CE-MRI fused to the simulation CT (CTsim) integrating information from the PET/CT. Three methods to delineate the PET volume were evaluated:manual ( PET man ), semiautomatic (42% threshold of SUV max , PET SUV 42 % ) and automatic adaptive thresholding method incorporating PET reconstruction parameters ( PET auto ) (iTA, TA). PET man volumes were delineated by the same nuclear medicine physician, while PET SUV 42 % and PET auto volumes were determined by medical physicists.The PET/CT, CE-RMI and CT sim were co-registered with a deformable image registration algorithm using the MIM Software.The overlapping region of MRI and PET man resulted in GTV common . Results The lesions had a median SUV max of 12.1 ± 6.8 (range:3.2–32.6).Overall, the GTV-MRI was larger than GTV-PET man in 7 patients (43.8%), smaller in 6 (37.5%) and almost the same in 3 (18.8%).The median value of the different volumes were:GTV-MRI = 14.3 ± 37.2 cc, GTV-PET man = 14.4 ± 47.0 cc , GTV common = 12.2 ± 33.6 cc , GTV-PET SUV 42 % = 8.3 ± 18.3 cc , GTV- PET auto = 11.3 ± 26.2 cc . GTV-PET SUV 42 % were always smaller than GTV-PET man ( Δ = - 51.0 ± 32.7 % ) and GTV-PET auto ( Δ = - 21.5 ± 12.7 % ) being variations in tumor heterogeneity not accounted for. Largest differences were observed for lesions showing high SD of SUV. The median difference between GTV-PET man and GTV-PET auto was 39.6 ± 29.5%. Conclusions 68 Ga-DOTATOC-PET/CT seems to improve the target volume delineation in skull base meningiomas, often leading to a reduction of GTV compared with MRI. The automatic adaptive thresholding delineation method may provide robust and reliable tool to help physician in segmenting PET images, reducing inter- and intra-observer variability.

Purpose To investigate possible correlation between absorbed dose (AD) and tumour response by means of Tumour Control Probability (TCP) in liver metastases treated with radioembolization (RE) with resin 90Y-microspheres. To assess response, the analysis of parameters from FDG-PET/CT has been preferred to RECIST criteria as metabolic response has proven to anticipate morphologic response. Methods Patients with chemo-refractory liver metastases from solid tumours scheduled to receive RE underwent FDG-PET/CT scan before and 6 weeks after RE. 99mTc-MAA (75–111 MBq) were injected 2 weeks before RE to perform dosimetry based on SPECT fused to contrast CT. Response assessment was based on PERCIST criteria. Variation (%) of PET parameters versus basal examination were evaluated to establish Complete-Response (CR), Partial-Response (PR), Stable-Disease (SD), Progressive-Disease (PD). Results 22 patients with hepatic lesions from colon-rectal (11), breast (7), ovary (1), endometrial (1), parotid (1) cancer, cholangiocarcinoma (1) were suitable for analysis. All patients received a single RE treatment (median activity: 1.7 GBq; range: 0.6–2.9 GBq). Median (range) tumour AD: 100(30–443) Gy. Metabolic response rate of lesions based on PERCIST were: CR = 31%; PR = 28%; SD = 24%; PD = 17%. Two different TCP curves were obtained by probit regression when considering: i) endpoint-1: PR or CR; ii) endpoint-2: CR only (p = 220 Gy only CR were observed. TCP of 50%, 75%, 100% were obtained at: i) 108, 120, 165 Gy; ii) 135, 160, 225 Gy. Conclusions Despite the variety of primary tumours, relatively low cohort of patients, and uncertainty of dosimetry with 99mTc-MAA, our preliminary data provided evidence of correlation between response based on PET/CT and AD. These encouraging results need to be confirmed with more ample dataset and, possibly, tumour type differentiation. Other PET/CT parameters such as the metabolic tumour volume and tumour lesion glycolysis are being considered for comparison with PERCIST and possible improved correlations.

OBJECTIVE The aim of the present study is to evaluate the accuracy of Positron Emission Tomography/Computed Tomography (PET/CT) with Fluorodeoxyglucose ([18F]FDG) to predict treatment response in patients with locally advanced rectal cancer (LARC) during neoadjuvant chemoradiotherapy. PATIENTS AND METHODS Forty-one LARC patients performed [18F]FDG-PET/CT at baseline (PET0). All patients received continuous capecitabine concomitant to radiotherapy on the pelvis, followed by intermittent capecitabine until two weeks before curative surgery. [18F]FDG-PET/CT was also carried out at 40 Gy-time (PET1) and at the end of neoadjuvant therapy (PET2). PET imaging was analysed semi-quantitatively through the measurement of maximal standardised uptake value (SUVmax) and the tumour volume (TV). Histology was expressed through pTNM and Dworak tumor regression grading. Patients were categorised into responder (downstaging or downsizing) and non-responder (stable or progressive disease by comparison pretreatment parameters with clinical/pathological characteristics posttreatment/after surgery). Logistic regression was used to evaluate SUVmax and TV absolute and percent reduction as predictors of response rate using gender, age, and CEA as covariates. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Survivals were compared by the Log-Rank test. RESULTS Twenty-three responders (9 ypCR, 14 with downstaged disease) and 18 non-responders showed differences in terms of both early and posttreatment SUVmax percent reduction (median comparison: responder = 63.2%, non-responder = 44.2%, p = 0.04 and responder = 76.9%, non-responder = 61.6%, p = 0.06 respectively). The best predictive cut-offs of treatment response for early and posttreatment SUVmax percent reduction were ≥57% and ≥66% from baseline (p = 0.02 and p = 0.01 respectively). CONCLUSIONS [18F]FDG-PET/CT is a reliable technique for evaluating therapy response during neoadjuvant treatment in LARC, through a categorical classification of the SUV max reduction during treatment.

Purpose: A radio-guided surgery technique with beta- -emitting radio-tracers was suggested to overcome the effect of the large penetration of gamma radiation. The feasibility studies in the case of brain tumors and abdominal neuro-endocrine tumors were based on simulations starting from PET images with several underlying assumptions. This paper reports, as proof-of-principle of this technique, an ex-vivo test on a meningioma patient. This test allowed to validate the whole chain, from the evaluation of the SUV of the tumor, to the assumptions on the bio-distribution and the signal detection. Methods: A patient affected by meningioma was administered 300 MBq of 90Y-DOTATOC. Several samples extracted from the meningioma and the nearby Dura Mater were analyzed with a beta- probe designed specifically for this radio-guided surgery technique. The observed signals were compared both with the evaluation from the histology and with the Monte Carlo simulation. Results: we obtained a large signal on the bulk tumor (105 cps) and a significant signal on residuals of $\sim$0.2 ml (28 cps). We also show that simulations predict correctly the observed yields and this allows us to estimate that the healthy tissues would return negligible signals (~1 cps). This test also demonstrated that the exposure of the medical staff is negligible and that among the biological wastes only urine has a significant activity. Conclusions: This proof-of-principle test on a patient assessed that the technique is feasible with negligible background to medical personnel and confirmed that the expectations obtained with Monte Carlo simulations starting from diagnostic PET images are correct., Comment: 17 pages, 4 Figs, Accepted by Physica Medica

Purpose A very promising technique for radio-guided surgery (RGS) based on β -radiation is being developed. The lower background, with respect to the established approach with high penetrant γ radiation, can allow for a large diffusion of such a technique and extending the RGS to cases with a large uptake of surrounding healthy organs, such as abdominal and brain neoplastic disease or tumor of infancy. Methods To validate the β -RGS feasibility study, tests on ex-vivo specimens of brain meningioma and gastro-entero-pancreatic neuroendocrine tumors have been performed. These clinical cases were selected between the tumors known to express receptors to a β -emitting radio-tracer already in use in the clinical routine: 90Y-labelled DOTATOC. Voluntary patients were enrolled according to the standard uptake value (SUV) and the expected tumor-to-non-tumor ratios (TNR) estimated from PET/CT images after administration of 68 Ga-DOTATOC. All of them gave written informed consent to participate in the clinical trial, already approved by the Ethics Committee. After administration of a low activity (about 2.5 mCi) of 90Y-DOTATOC, the extracted ex-vivo specimens and the healthy tissue around the lesions were examined to assess the correlation between the counting rates measured by the developed β -detecting probe and the expected 90Y activity. Results All the neoplastic samples were correctly identified. A dependence of the counting rate both on the volume V and on the total activity of the sample were observed. Even injecting as low as 1.4 MBq/kg of radio-tracer, tumor remnants of 0.1 ml would be detectable in few seconds. Conclusions The results of the clinical tests showed the validity of the underlying assumptions and strengthening the feasibility studies already published. Small radiopharmaceutical activity is required to detect a tumor remnant as expected due to the low background rates. The negligible medical staff exposure was also confirmed.

Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumours (NET) has been explored for almost two decades, but there are still few trials that have exclusively investigated well-differentiated and moderately differentiated NET arising from the respiratory tree. Thus, the aim of this study was to explore the outcome in patients affected by bronchopulmonary carcinoid (BPC) following PRRT.We retrospectively analysed 114 patients with advanced stage BPC consecutively treated with PRRT at the European Institute of Oncology, Milan, from 1997 to 2012 and followed until October 2014. The objective responses, overall survival (OS) and progression-free survival (PFS) were rated, and three different PRRT protocols ((90)Y-DOTATOC vs. (177)Lu-DOTATATE vs. (90)Y-DOTATOC + (177)Lu-DOTATATE) were compared with regard to their efficacy and tolerability.The median OS (evaluated in 94 of the 114 patients) was 58.8 months. The median PFS was 28.0 months. The (177)Lu-DOTATATE protocol resulted in the highest 5-year OS (61.4%). Morphological responses (partial responses + minor responses) were obtained in 26.5% of the cohort and were associated with longer OS and PFS. The (90)Y-DOTATOC + (177)Lu-DOTATATE protocol provided the highest response rate (38.1%). Adverse events were mild in the majority of patients. However, haematological toxicity negatively affected survival. No severe (grade 3/4) serum creatinine increase was observed. Patients treated with (90)Y-DOTATOC alone more frequently showed a mild/moderate decrease in renal function. In patients treated with chemotherapy before PRRT had a shorter OS and PFS, and a higher risk of developing nephrotoxicity.In a large cohort of patients with advanced BPC treated in a "real-world" scenario and followed up for a median of 45.1 months (range 2-191 months), PRRT proved to be promising in prolonging survival and delaying disease progression. Despite the potential selection biases, considering the risk-benefit ratio, (177)Lu-DOTATATE monotherapy seems the best option for PRRT. Our results indicate that the use of PRRT in earlier stages of the disease could provide a more favorable outcome.

A 35-year-old woman, already treated with surgery, chemotherapy, and radiotherapy for a ductal carcinoma of the left breast, underwent an (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) scan for an increase of the serum markers carcinoembryonic antigen (CEA) and cancer antigen 15.3 (CA15.3). The scan showed multiple FDG-avid lesions in the liver and bone. The images also detected two areas of uptake in the dorsal and lumbar spinal cord, which were suspicious for metastases; magnetic resonance imaging (MRI) confirmed these lesions.

Autonomous functioning thyroid nodules (AFTN), defined as "hot nodules" at thyroid scan, are often cured by radioiodine treatment. The aim of our study was to investigate the long-term outcome in patients treated with an 131I calculated dose, to identify a possible "size-tailored" dose, and to simplify follow-up procedures.Retrospective analysis was carried out on 1402 cases, covering a period of 50 years, of AFTN treated with an 131I calculated dose. Our study focused on nodular size and mean administered dose. Concordance between thyroid scan and serum TSH levels at 3-6 months from treatment was considered.A single 131I dose was effective for the vast majority of patients (93%). The outcome was influenced by nodular size. On the basis of the Italian dose limit for outpatient treatment, our population was divided into subgroups according to administered doses (more or less than 16 mCi) and nodular dimensions: no differences in outcome were observed for each class of nodule size. A dose ≤10 mCi was effective on the smaller nodules (50.1% of our population). The agreement between TSH and scan after treatment was 90.3% at 3 months and 94.5% at 6 months.131I therapy with a calculated dose is an effective treatment of AFTN. If a fixed dose is chosen, 16 mCi is often resolutive and for nodules3 cm a dose of 10 mCi can suffice. Nodules5 cm are eligible for surgery. TSH is the only parameter required to evaluate the outcome.

To evaluate the role of 24 h/4 h uptake ratio (UR) in response to radioiodine-131 ((131)I) therapy in patients with autonomously functioning thyroid nodules (AFTN).A total of 1402 consecutive hyperthyroid patients were treated with (131)I, between 1958 and 2005. Therapeutic doses (D) were calculated according to the formula: D = weight of nodule x dose per gram of nodular tissue (q)/24 h (131)I uptake. The ratios of the 24 and 4 h uptake were retrospectively calculated and the patients were grouped according to outcome and q into three groups of UR (or =1.25; 1.26-1.68;or =1.69) by means of terziles.Of the 1402 patients, 95 did not respond to (131)I treatment while 93/1307 developed hypothyroidism. Most non-responders (55.8%) had URor =1.25, while many hypothyroid patients (66.7%) had URor =1.69 (chi (2): P0.001). As q increased, the proportion of successfully treated patients increased (level of significance) only in the group with URor =1.25; while in the other two terziles, with increasing dose per gram of nodular tissue, the number of successfully treated patients did not increase (level of significance). The cumulative incidence of hypothyroidism was 2.2% at the 1st year after (131)I treatment, increasing to 13.9% at 5 years and 26.2% at 10 years.The (131)I UR can predict the outcome of (131)I treatment in AFTN and may have utility in modifying treatment in some patients to limit post-radioiodine induced hypothyroidism and treatment failures in order to achieve euthyroidism.

Radioiodine uptake is rarely observed in normal non-lactating breast tissue. Investigation of the in vivo regulation of iodide uptake in breast tissue may be useful for the induction of radioiodine uptake in breast cancer tissue for diagnostic and therapeutic purposes.We report the cases of two post-menopausal women who underwent radioiodine therapy for papillary thyroid carcinoma and in whom breast uptake of radioiodine on post-therapy whole body scan (WBS) was observed.In both patients, elevated serum prolactin levels (123 ng/mL in patient 1 and 48 ng/mL in patient 2) were documented at the time when radioiodine uptake in the breast was observed. The hyperprolactinemia was due to prolonged treatment with the anti-dopaminergic neuroleptic risperidone in Case 1, and chronic renal failure in Case 2. When prolactin levels were normalized (by withdrawal of risperidone in Case 1 and with cabergoline in Case 2), breast tissue uptake was no longer evident on WBS.These cases provide the first documented correlation between serum levels of endogenous prolactin and radioiodine uptake by involuted breast tissue in humans.

Recombinant human TSH (rhTSH) has been recently suggested for radioiodine ablation in patients with differentiated thyroid cancer (DTC). To date, studies are still not available about the effectiveness of rhTSH stimulation depending on the age, since serum TSH clearance may be different in younger and in older patients. The aim of this study was to investigate the influence of age to serum TSH levels after rhTSH stimulation and thyroid hormone withdrawal (THW). We retrospectively evaluated two groups of consecutive DTC patients: group 1 (311 patients, age 49.0+/-13.6 years, ranging 15-86) underwent rhTSH stimulation 6-12 months after thyroid ablation (rhTSH-group); group 2 (84 patients, age 46.9+/-13.5 years, ranging 20-77) was followed by THW (THW-group). The influence of age, gender, body mass index and body surface area to serum TSH levels were evaluated in both groups. RhTSH-group: on day 5 (d5), TSH levels were 32.7+/-21.4 microU/ml (range 0.8-136.6). By univariate analysis, d5-TSH was positively related to age (r=0.27, p=0.0001) and no correlations were found with the other parameters. At multivariate analysis, both age and gender (female) were independently associated with d5-TSH levels. THW-group: after thyroid hormone withdrawal, TSH levels were 71.1+/-36.4 microU/ml (range 8.5-200). At univariate analysis, only age was significantly and negatively related to serum TSH levels (r=-0.31, p=0.004). Our data indicate that age and gender seem to positively influence serum TSH levels after rhTSH stimulation. An opposite effect of age on serum TSH levels has been observed after THW. Therapeutic implications ((131)I-treatment) of these findings have to be better investigated in prospective studies.