A new mobile self-dispensing and administering system for 18F-FDG: evaluation of operator dose reduction.

PURPOSE: Recently new mobile systems for dispensing positron emitters have been produced, designed to guarantee dispensing cycles in an aseptic environment. The aim of the present work was to assess the advantage of one of these systems in radiation protection of operators in clinical settings. METHODS: Recently, in our centre the new self-dispensing system named KARL100 by Tema Sinergie was adopted for 18F-FDG radiopharmaceuticals. The system is associated with an automatic Rad-inject infuser. The system that was previously used was a fixed isolator NMC DSI (Tema Sinergie), equipped with a µDDS-An activity fractioning system, together with a pneumatic post for the syringe delivery. The dosimetric evaluations on both systems were carried out through environmental measurements with an ionisation chamber and with the use of personal dosimeters. RESULTS: The operations of preparation and administration of 18F-FDG dose to the patient, with the use of Karl100 + RadInject, involve exposures much lower than those obtained by the fixed isolator. The average body exposure of the technician was reduced by 31%, and for the physician by 77%. On the extremities, the equivalent dose to the hands of the technician was reduced by 78%, and for the physician by 96%. Also the additional dosimeters worn by the technician confirmed the estimated environmental assessments. CONCLUSIONS: The exposures of the working personnel were significantly reduced with the introduction of the new KARL100 system.

Value of (18)F-FDG PET for Predicting Response to Neoadjuvant Therapy in Rectal Cancer: Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study was to assess the predictive value of (18)F-FDG PET/ CT for pathologic response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. MATERIALS AND METHODS: A systematic search was performed (PubMed and Cochrane databases) for potentially relevant studies up to January 2014. Pooled sensitivity and specificity were calculated. The AUCs of the global cohort and for "major response," "complete response," "only PET after chemoradiotherapy," "ad interim PET," "major response excluding ad interim studies," "complete response excluding ad interim studies," "response index (RI)," "posttreatment maximum standardized uptake value (SUV(max) post)," "visual response analysis (VRA)," "percentage reduction of the total lesion glycolysis (ΔTLG)," and "percentage reduction of the metabolic tumor volume (ΔMTV)" were analyzed. Heterogeneity was explored for multiple variables. Pooled prevalence and 95% CI were calculated. RESULTS: Thirty-four of 131 (26%) initial articles met the inclusion criteria. Those articles included 1526 patients. PET/CT showed good pooled accuracy both in the global cohort (pooled sensitivity, 73%; pooled specificity, 77%; pooled AUC, 0.83) and for subgroups. Pooled accuracy was similar for early PET restaging and at 1 and 2 weeks after beginning chemoradiotherapy (pooled sensitivity, 84%; pooled specificity, 81%; pooled AUC, 0.89). The major response group showed similar sensitivity to the complete response group (74% and 71%, respectively). RI, SUV(max), and VRA were the most frequent parameters used. Pooled RI and SUV(max) postcutoff values were 63% and 4.4. Pooled time to PET during and after chemoradiotherapy was 1.5 and 6.5 weeks, respectively. CONCLUSION: This meta-analysis supports the use of FDG PET for restaging locally advanced rectal cancer.

Is the detection rate of 18F-choline PET/CT influenced by androgen-deprivation therapy?

PURPOSE: To evaluate if the detection rate (DR) of (18)F-choline (18F-CH) PET/CT is influenced by androgen-deprivation therapy (ADT) in patients with prostate cancer (PC) already treated with radical intent and presenting biochemical relapse. MATERIALS AND METHODS: We have retrospectively evaluated (18)F-CH PET/CT scans of 325 consecutive PC patients enrolled in the period November 2009 to December 2012 previously treated with radical intent and referred to our centre to perform (18)F-CH PET/CT for biochemical relapse. Two different groups of patients were evaluated. group A included the whole sample of 325 patients (mean age 70 years, range: 49-86) who presented trigger PSA between 0.1 and 80 ng/ml (mean 5.5 ng/ml), and group B included 187 patients (mean age 70 years, range 49-86) with medium-low levels of trigger PSA ranging between 0.5 and 5 ng/ml (mean PSA 2.1 ng/ml); group B was chosen in order to obtain a more homogeneous group of patients in terms of PSA values also excluding both very low and very high PSA levels avoiding the "a priori" higher probability of negative or positive PET scan, respectively. At the time of examination, 139 patients from group A and 72 patients from group B were under ADT: these patients were considered to be hormone-resistant PC patients because from their oncologic history (>18 months) an increase of PSA levels emerged despite the ongoing ADT. The relationship between (18)F-CH PET/CT findings and possible clinical predictors was investigated using both univariate and multivariate binary logistic regression analyses, including trigger PSA and ADT. RESULTS: Considering the whole population, overall DR of (18)F-CH PET was 58.2 % (189/325 patients). In the whole sample of patients (group A), both at the univariate and multivariate logistic regression analysis, trigger PSA and ADT were significantly correlated with the DR of (18)F-CH PET (p < 0.05). Moreover, the DR in patients under ADT (mean PSA 7.8 ng/ml) was higher than in patients not under ADT (mean PSA 3.9 ng/ml), (DR was 70.5 % and 48.9 %, respectively; p < 0.001), therefore, demonstrating the existence of a significant correlation between the DR of (18)F-CH PET and ADT. In group B patients only trigger PSA resulted a reliable predictor of the (18)F-CH positivity, since ADT was not correlated to the DR of (18)F-CH PET (p = 0.061). Also in group B the DR of (18)F-CH PET in patients under ADT was higher than in patients not under ADT (65.3 % and 51.3 %, respectively) but the difference was not significant without a statistically significant correlation in the Mann Whitney test (p = 0.456) therefore, suggesting the lack of correlation between DR (18)F-CH PET/CT and ADT. CONCLUSION: Similarly to previous published studies, in our series the overall DR of (18)F-CH PET/CT was 58 % and was significantly correlated to trigger PSA. The most important finding of the present study is that ADT does not negatively influence DR of (18)F-CH PET/CT in PC patients with biochemical relapse; therefore, it can be suggested that it is not necessary to withdraw ADT before performing (18)F-CH PET/CT.

Molecular imaging of pulmonary nodules.

OBJECTIVE: Lung nodules can be benign or malignant, reflecting many possible causes, ranging from inflammatory and infectious processes to neoplasms. Incidental detection on chest x-ray or thoracic CT often requires further evaluation by imaging or invasive procedures. CONCLUSION: Currently, 18F-FDG PET/CT offers both anatomic and metabolic characterization of lung nodules. Fluorine-18-thymidine, 11C-methionine, 68Ga-DOTA-somatostatin analogs, and 18F-dihydroxyphenylalanine may offer additional molecular information useful for diagnosis and treatment planning.

Role of ¹8F-choline PET/CT in suspicion of relapse following definitive radiotherapy for prostate cancer.

PURPOSE: The aims of the study were (a) to evaluate the diagnostic role, by means of positive detection rate (PDR), of ¹8F-choline (CH) positron emission tomography (PET)/CT in patients with prostate cancer treated with radiotherapy, with curative intent, and suspicion of relapse during follow-up, (b) to correlate the PDR with trigger prostate-specific antigen (PSA), (c) to investigate the possible influence of androgen deprivation therapy (ADT) at the time of scan on PDR and (d) to assess distribution of metastatic spread. METHODS: ¹8F-CH PET/CT exams from 46 consecutive patients (mean age 71.3 years, range 51-84 years) with prostate cancer (mean Gleason score 6.4, range 5-8) previously treated by definitive radiotherapy and with suspicion of relapse with negative or inconclusive conventional imaging were retrospectively evaluated. Of the 46 patients, 12 were treated with brachytherapy and 34 with external beam radiation therapy. Twenty-three patients were under ADT at the time of the examination. Trigger PSA was measured within 1 month before the exam (mean value 6.5 ng/ml, range 1.1-49.4 ng/ml). Patients were subdivided into four groups according to their PSA level: 1.0 < PSA ≤ 2.0 ng/ml (11 patients), 2.0 < PSA ≤ 4.0 ng/ml (16 patients), 4.0 < PSA ≤ 6.0 ng/ml (9 patients) and PSA > 6.0 ng/ml (10 patients). Correlation between ADT and PDR was investigated as well as between PSA and distribution of metastatic spread. RESULTS: The overall PDR of ¹8F-CH PET/CT was 80.4% (37/46 patients), increasing with the increase of trigger PSA. PDR of ¹8F-CH PET/CT is not influenced by ADT (p = 0.710) even if PET performed under ADT demonstrated an overall higher PDR (82.6%). The majority of the patients (59%, 22/37 patients) showed local relapse only, confined to the prostatic bed; 22% of the PET/CT-positive patients (8/37 patients) showed distant relapse only (bone localizations in all of them), while the remaining 19% (7/37 patients) showed both local and distant (lymph node and bone) spread. CONCLUSION: ¹8F-CH PET/CT showed a high overall detection rate (80%), proportional to the trigger PSA (both for local and distant relapse) not influenced by ADT. ¹8F-CH PET/CT is proposed as a first-line imaging procedure in restaging prostate cancer patients primarily treated with radiotherapy.

Fifteen different 18F-FDG PET/CT qualitative and quantitative parameters investigated as pathological response predictors of locally advanced rectal cancer treated by neoadjuvant chemoradiation therapy.

PURPOSE: The aim of this study was to correlate qualitative visual response and various PET quantification factors with the tumour regression grade (TRG) classification of pathological response to neoadjuvant chemoradiotherapy (CRT) proposed by Mandard. METHODS: Included in this retrospective study were 69 consecutive patients with locally advanced rectal cancer (LARC). FDG PET/CT scans were performed at staging and after CRT (mean 6.7 weeks). Tumour SUVmax and its related arithmetic and percentage decrease (response index, RI) were calculated. Qualitative analysis was performed by visual response assessment (VRA), PERCIST 1.0 and response cut-off classification based on a new definition of residual disease. Metabolic tumour volume (MTV) was calculated using a 40 % SUVmax threshold, and the total lesion glycolysis (TLG) both before and after CRT and their arithmetic and percentage change were also calculated. We split the patients into responders (TRG 1 or 2) and nonresponders (TRG 3-5). RESULTS: SUVmax MTV and TLG after CRT, RI, ΔMTV% and ΔTLG% parameters were significantly correlated with pathological treatment response (p < 0.01) with a ROC curve cut-off values of 5.1, 2.1 cm(3), 23.4 cm(3), 61.8 %, 81.4 % and 94.2 %, respectively. SUVmax after CRT had the highest ROC AUC (0.846), with a sensitivity of 86 % and a specificity of 80 %. VRA and response cut-off classification were also significantly predictive of TRG response (VRA with the best accuracy: sensitivity 86 % and specificity 55 %). In contrast, assessment using PERCIST was not significantly correlated with TRG. CONCLUSION: FDG PET/CT can accurately stratify patients with LARC preoperatively, independently of the method chosen to interpret the images. Among many PET parameters, some of which are not immediately obtainable, the most commonly used in clinical practice (SUVmax after CRT and VRA) showed the best accuracy in predicting TRG.

Radiomics and theranostics with molecular and metabolic probes in prostate cancer: toward a personalized approach.

INTRODUCTION: In the last decade, two new radionuclide-based therapies, 223Radichloride and radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA), have been approved by the regulatory authorities for the management of castrate-resistant prostate cancer (PCa). AREAS COVERED: The basic principles of PCa molecular imaging are illustrated, with a particular attention to the combined use of diagnosis and therapy in a unique approach (the so-called theranostics) for response prediction and assessment in patients submitted to 223Radichloride or PSMA targeted therapies. In this perspective, the potential of radiomics, an emerging discipline based on the extraction of quantitative features from medical images, is covered. EXPERT OPINION: Theranostic metabolic and molecular probes have been successfully applied to predict and monitor response to radionuclide-based therapies. In particular, both 99mTc-MDP and 18F-NaF resulted useful tools for personalized dosimetry and prognostic stratification before 223Ra-therapy, while PSMA-ligands, alone or in combination with 18F-FDG, provided valuable information to select patients who are more likely to benefit from RLT and getting information on PCa grade of differentiation and aggressiveness. In spite of its high potential, PET-radiomics for PCa is still at an embryonic phase and needs further validation.

Molecular imaging of PARP in cancer: state-of-the-art.

INTRODUCTION: Poly-ADP-ribose-polymerase inhibitors (PARPi), which exploit the processes of so-called 'synthetic lethality,' have been successfully implemented in oncological practice. However, not all patients respond to PARPi, and there is an unmet need for noninvasive biomarkers suitable for patient selection and monitoring during PARPi therapy. AREAS COVERED: The first clinical applications of molecular imaging with positron emission tomography/computed tomography (PET/CT) with [18F]-FluorThanatrace ([18F]-FTT) and [18F]-PARPi, highly effective PARP-ligands, in patients with several malignancies (head and neck, ovarian, prostate, and breast cancer) are covered, with a particular focus on its potential for pre-treatment selection and follow-up. EXPERT OPINION: By a search made on the most common database, such as PubMed and Google Scholar in a period from January 2010 and 2023, first clinical evidence suggests that PET/CT with [18F]-FTT and [18F]-PARPi might represent a reliable tool for in vivo imaging and quantification of PARP-1 expression in ovarian, prostate, breast, head, and neck cancer, supporting their potential usefulness for patient selection before PARPi-therapies. In addition, a reduction in [18F]-FTT uptake has been registered after therapy initiation and seems to be correlated with patient outcome after PARPi-based regimens. Further studies are needed to better address the value of PARPI-radiolabeled PET imaging in these clinical settings, especially as it concerns technical features such as optimal scan modality (dynamic vs. static) and timing.

Cavernous Hepatic Hemangioma at 18F-Choline Positron Emission Tomography-Computed Tomography: Be Aware of the Pitfall.

We report a case of a patient performing a positron emission tomography-computed tomography (PET-CT) scan with [18F]F-Choline for biochemical relapse (Prostate specific antigen (PSA) 1.2 ng/ml) of prostate cancer. Two large areas of focal uptake with a cold core within the liver were observed. A contrast-enhanced ultrasound scan performed after the PET scan characterized these lesions as cavernous hepatic hemangiomas, and therefore, a biopsy was not performed; 3 years of follow-up and PET and MRI finding stability confirmed the benignity of their nature.

Comparison of MRI vs. [18F]FDG PET/CT for Treatment Response Evaluation of Primary Breast Cancer after Neoadjuvant Chemotherapy: Literature Review and Future Perspectives.

The purpose of this systematic review was to investigate the diagnostic accuracy of [18F]FDG PET/CT and breast MRI for primary breast cancer (BC) response assessment after neoadjuvant chemotherapy (NAC) and to evaluate future perspectives in this setting. We performed a critical review using three bibliographic databases (i.e., PubMed, Scopus, and Web of Science) for articles published up to the 6 June 2023, starting from 2012. The Quality Assessment of Diagnosis Accuracy Study (QUADAS-2) tool was adopted to evaluate the risk of bias. A total of 76 studies were identified and screened, while 14 articles were included in our systematic review after a full-text assessment. The total number of patients included was 842. Eight out of fourteen studies (57.1%) were prospective, while all except one study were conducted in a single center. In the majority of the included studies (71.4%), 3.0 Tesla (T) MRI scans were adopted. Three out of fourteen studies (21.4%) used both 1.5 and 3.0 T MRI and only two used 1.5 T. [18F]FDG was the radiotracer used in every study included. All patients accepted surgical treatment after NAC and each study used pathological complete response (pCR) as the reference standard. Some of the studies have demonstrated the superiority of [18F]FDG PET/CT, while others proved that MRI was superior to PET/CT. Recent studies indicate that PET/CT has a better specificity, while MRI has a superior sensitivity for assessing pCR in BC patients after NAC. The complementary value of the combined use of these modalities represents probably the most important tool to improve diagnostic performance in this setting. Overall, larger prospective studies, possibly randomized, are needed, hopefully evaluating PET/MR and allowing for new tools, such as radiomic parameters, to find a proper place in the setting of BC patients undergoing NAC.

The Role of Molecular Imaging in Patients with Brain Metastases: A Literature Review.

Over the last several years, molecular imaging has gained a primary role in the evaluation of patients with brain metastases (BM). Therefore, the "Response Assessment in Neuro-Oncology" (RANO) group recommends amino acid radiotracers for the assessment of BM. Our review summarizes the current use of positron emission tomography (PET) radiotracers in patients with BM, ranging from present to future perspectives with new PET radiotracers, including the role of radiomics and potential theranostics approaches. A comprehensive search of PubMed results was conducted. All studies published in English up to and including December 2022 were reviewed. Current evidence confirms the important role of amino acid PET radiotracers for the delineation of BM extension, for the assessment of response to therapy, and particularly for the differentiation between tumor progression and radionecrosis. The newer radiotracers explore non-invasively different biological tumor processes, although more consistent findings in larger clinical trials are necessary to confirm preliminary results. Our review illustrates the role of molecular imaging in patients with BM. Along with magnetic resonance imaging (MRI), the gold standard for diagnosis of BM, PET is a useful complementary technique for processes that otherwise cannot be obtained from anatomical MRI alone.

PSMA PET/CT in Castration-Resistant Prostate Cancer: Myth or Reality?

BACKGROUND: prostate-specific membrane antigen (PSMA) ligand PET has been recently incorporated into international guidelines for several different indications in prostate cancer (PCa) patients. However, there are still some open questions regarding the role of PSMA ligand PET in castration-resistant prostate cancer (CRPC). The aim of this work is to assess the clinical value of PSMA ligand PET/CT in patients with CRPC. RESULTS: PSMA ligand PET has demonstrated higher detection rates in comparison to conventional imaging and allows for a significant reduction in the number of M0 CRPC patients. However, its real impact on patients' prognosis is still an open question. Moreover, in CRPC patients, PSMA ligand PET presents some sensitivity and specificity limitations. Due to its heterogeneity, CRPC may present a mosaic of neoplastic clones, some of which could be PSMA-/FDG+, or vice versa. Likewise, unspecific bone uptake (UBU) and second primary neoplasms (SNPs) overexpressing PSMA in the neoangiogenic vessels represent potential specificity issues. Integrated multi-tracer imaging (PSMA ligand and [18F]FDG PET) together with a multidisciplinary discussion could allow for reaching the most accurate evaluation of each patient from a precision medicine point of view.

Lutathera® Orphans: State of the Art and Future Application of Radioligand Therapy with 177Lu-DOTATATE.

Lutathera® is the first EMA- and FDA-approved radiopharmaceutical for radioligand therapy (RLT). Currently, on the legacy of the NETTER1 trial, only adult patients with progressive unresectable somatostatin receptor (SSTR) positive gastroenteropancreatic (GEP) neuroendocrine neoplasms (NET) can be treated with Lutathera®. Conversely, patients with SSTR-positive disease arising from outside the gastroenteric region do not currently have access to Lutathera® treatment despite several papers in the literature reporting the effectiveness and safety of RLT in these settings. Moreover, patients with well-differentiated G3 GEP-NET are also still "Lutathera orphans", and retreatment with RLT in patients with disease relapse is currently not approved. The aim of this critical review is to summarize current literature evidence assessing the role of Lutathera® outside the approved indications. Moreover, ongoing clinical trials evaluating new possible applications of Lutathera® will be considered and discussed to provide an updated picture of future investigations.

Is there a role for ¹¹C-choline PET/CT in the early detection of metastatic disease in surgically treated prostate cancer patients with a mild PSA increase <1.5 ng/ml?

PURPOSE: The aim of this study was to evaluate the potential usefulness of whole-body (11)C-choline PET/CT in the re-staging of prostate cancer (PC) patients previously treated with radical prostatectomy (RP), who presented a mild increase of prostate-specific antigen (PSA) <1.5 ng/ml (early biochemical relapse) during follow-up (FU). METHODS: We evaluated 102 consecutive patients (mean age = 68 years, range = 54-82 years) previously treated with RP and who presented during FU a mild increase of trigger PSA serum levels <1.5 ng/ml: mean 0.86 ± 0.40 ng/ml (range 0.2-1.5) and median 0.93 ng/ml (range 0.67-1.10). In this patient series (11)C-choline PET/CT was used as the first imaging examination at the time of the detection of a mild serum PSA increase <1.5 ng/ml. (11)C-Choline PET/CT was performed following standard procedures in our centre. At the time of PET/CT, 86 patients were not receiving any pharmacologic treatment, while 16 were under anti-androgenic therapy. Positive PET findings were validated by: (a) transrectal ultrasound (TRUS)-guided biopsy in cases of local recurrence, (b) surgical lymphadenectomy, (c) other imaging procedures or (d) FU lasting for at least 12 months. Univariate and multivariate analyses were used to evaluate the following variables: age, TNM staging, Gleason score, time from RP to the biochemical relapse, anti-androgen therapy at the time of (11)C-choline PET/CT scan, trigger PSA value and PSA kinetics, i.e. PSA doubling time (PSAdt) and PSA velocity (PSAvel), in order to assess the significant predictive factors related to the findings of a positive (11)C-choline PET/CT scan. RESULTS: Overall, (11)C-choline PET/CT showed positive findings in 29 of 102 patients (28% of cases). In detail, (11)C-choline PET/CT detected: local relapse in 7 patients, bone metastases in 13 patients (4 single and 9 multiple) and lymph node metastases in 9 patients (6 single and 3 multiple). Positive PET findings were validated by: (a) TRUS-guided biopsy in 7 patients with local recurrence, (b) surgery and lymphadenectomy in 3 patients, (c) other targeted imaging procedures (MR or bone scan) in 5 patients and (d) clinical FU lasting a minimum of 12 months and including also a contrast-enhanced CT (CECT), an MR, a bone scan and a repeated (11)C-choline PET/CT in 14 patients. Age, time to biochemical relapse (TTR), initial T staging, Gleason score and trigger PSA were not statistically significant in predicting a positive (11)C-choline PET/CT scan both at univariate and multivariate analysis. Instead, PSA kinetics (PSAdt and PSAvel), N status and anti-androgenic therapy at the time of PET scan were statistically significant predictive factors at univariate analysis. Of note, only PSAdt and initial N status were found to be significant and independent predictive factors at multivariate analysis. The mean PSAdt in PET-positive patients was 4.34 months (SD 2.82) while in PET-negative patients it was 13.30 months (SD 9.75) (p = 0.0001). The optimal threshold for PSAdt established by receiver-operating characteristic (ROC) analysis was 7.25 months (AUC 0.85; 95% confidence interval 0.77-0.91) providing 93% sensitivity, 74% specificity, 60% positive predictive value and 96% negative predictive value. CONCLUSION: In our study, (11)C-choline PET/CT was able to detect recurrent disease in 28% of the patients with mild biochemical relapse characterized by very low trigger PSA levels (PSA <1.5 ng/ml). Very interestingly (11)C-choline PET/CT detected distant unexpected metastases in 21% of the patients. At multivariate statistical analysis only PSAdt and node status were shown to be significant and independent predictive factors for positive (11)C-choline PET/CT. Therefore, (11)C-choline could be suggested to be performed early during initial biochemical relapse in patients presenting with fast PSA kinetics. The early detection of the site of recurrence could lead to a prompt instauration of the most appropriate treatment, i.e. local surgery or radiation treatment vs systemic treatment. In this view, one of the main advantages should be the avoidance of unnecessary local radiotherapy in those patients showing distant metastasis at (11)C-choline PET/CT.

Androgen deprivation therapy influences the uptake of 11C-choline in patients with recurrent prostate cancer: the preliminary results of a sequential PET/CT study.

PURPOSE: The influence of androgen deprivation therapy (ADT) on (11)C-choline uptake in patients with prostate cancer (PC) has not yet been clarified. The aim of our study was to investigate this issue by means of sequential (11)C-choline positron emission tomography (PET)/CT in patients with recurrent PC. METHODS: We retrospectively studied 14 recurrent PC patients (mean age 67 years, range 55-82) during follow-up after radical prostatectomy (RP) with rising serum prostate-specific antigen (PSA) levels. All patients had undergone at least two consecutive (11)C-choline PET/CT scans: the first (11)C-choline PET/CT before commencing ADT and the second (11)C-choline PET/CT after 6 months of ADT administration. RESULTS: The mean serum PSA level before ADT was 17.0 ± 44.1 ng/ml. After 6 months of ADT administration the PSA value significantly decreased in comparison to baseline (PSA = 2.4 ± 3.1 ng/ml, p < .025). Moreover, before starting ADT, 13 of 14 patients had positive (11)C-choline PET/CT for metastatic spread, while after 6 months of ADT administration in 9 of 14 patients (11)C-choline PET/CT became negative. CONCLUSION: These preliminary results suggest that ADT significantly reduces (11)C-choline uptake in androgen-sensitive PC patients.

Dosimetric optimization of nuclear medicine therapy based on the Council Directive 2013/59/EURATOM and the Italian law N. 101/2020. Position paper and recommendations by the Italian National Associations of Medical Physics (AIFM) and Nuclear Medicine (AIMN).

This recommendation by the Italian Associations of Nuclear Medicine (AIMN) and Medical Physics (AIFM) focuses on the dosimetric optimization of Nuclear Medicine Therapy (NMT) as clearly requested by the article 56 of the EURATOM Directive 2013/59 and its consequent implementation in article 158 in the Italian Law n. 101/2020. However, this statement must deal with scientific and methodological limits that still exist and, above all, with the currently available limited resources. This paper addresses these specific issues. It distinguishes among many possible kinds of NMT. For each type, dosimetric optimization is recommended or considered optional, according to the general criteria adopted in any human choice, i.e. a check of technical feasibility first, followed by a cost/benefit argument. The classification of therapies as standardized or non-standardized is presented. This is based on the complexity of the type of pathology, on the variability of the treatment outcome, and on the risks involved. According to the present document, which was officially delivered to Italian Health Ministry as necessary interpretation of the law, a therapeutic team can, in science and consciousness, overcome the indications of posology, to optimize and tailoring a treatment with dosimetry, on the basis of published national or international data or guidelines, without need of an Ethics Committee approval. Data collected in this way will provide additional evidence about optimal dosimetric reference values. As conclusion, a formal appeal is made to the European and National regulatory agencies for pharmaceuticals to obtain the official acknowledgment of this principle.

Recombinant human TSH and ablation of post-surgical thyroid remnants in differentiated thyroid cancer: the effect of pre-treatment with furosemide and furosemide plus lithium.

BACKGROUND AND AIM: Recombinant human TSH (rhTSH) can be used for post-surgical radioiodine (I-131) thyroid remnants ablation in differentiated thyroid cancer (DTC) patients after surgery. Debate exists in literature about the optimal amount of I-131 that should be given for obtaining an effective ablation and about the role of iodine pool during treatment. Therefore, the aim of the present study was to assess whether I-131 ablation during rhTSH stimulus can be improved by reducing the circulating iodine pool and by increasing thyroid cell uptake and retention of I-131 obtained by administering furosemide and lithium. METHODS: A total of 201 consecutive DTC patients were entered in the study: they were treated by total thyroidectomy and I-131 therapy during rhTSH stimulus to ablate thyroid remnants. Patients were divided into two groups according to the TNM stage: group 1 included patients in stage I-II who were treated with a low 30-mCi I-131 dose, while group 2 included patients in stage III-IV who were treated by a high 100-mCi I-131 dose. Moreover, both groups were further subdivided into three subgroups. Subgroup (a) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-thyroxine (LT4). Subgroup (b) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day withdrawal of L-T4, and after furosemide administration (25 mg/day orally) during the 3 days before I-131. Subgroup (c) included 45 patients from group 1 and 22 from group 2: they were treated with I-131 under rhTSH stimulus, following a short 4-day L-T4 withdrawal, and after administration of furosemide (25 mg/day orally) during the 3 days prior I-131 and lithium (450 mg/day orally) during the 3 days following I-131. Another group (group 3) of 20 patients characterized by a very low-risk cancer (unifocal tumor <1.0 cm in diameter, without extra-capsular extension, N0) was treated with a 30-mCi I-131 dose under rhTSH stimulus without performing the short 4-day L-4 withdrawal: this group was taken as the control. Follow-up was performed by neck ultrasonography (US), and Tg measurement and I-131 WBS under rhTSH stimulus. RESULTS: Among the patients from group 1, those pre-treated with furosemide or with furosemide plus lithium showed a better outcome of ablation both in terms of undetectable Tg values (97.7% and 95.5 % vs. 79.5%, p < 0.05) and of WBS negativity (97.7% vs. 81.8%, p < 0.05) during the rhTSH stimulus. No similar findings were observed in group 2 patients. Moreover, in patients from group 3 (I-131 30 mCi, without L-T4 withdrawal), the outcome of ablation was significantly lower in comparison to patients from group 1 (I-131 30 mCi, with L-T4 withdrawal) in terms of undetectable Tg during the rhTSH stimulus (55.0%, p < 0.001). CONCLUSION: rhTSH is highly effective for post-surgical thyroid remnant ablation in low-risk cancer patients using the low 30-mCi dose protocol combined with the short 4-day withdrawal of L-T4. Moreover, in these patients the pre-treatment with furosemide seems to play an important role to further improve the outcome of ablation by reducing the iodine pool.

Radioguided surgery and systemic radionuclide therapy of neuroendocrine tumours.

Neuroendocrine tumours (NETs) may be fatal, though at a significantly slower pace than their exocrine counterparts. Nuclear medicine procedures for diagnosis and treatment of NETs are based on expression of somatostatin receptors. Radioguided surgery is a new method for diagnosing and treating many tumours and uses introperative gamma probes. The use and development of intraoperative gamma probes in the last 10 years has enabled the development of minimally invasive procedures in oncological surgery, with an improvement in both the survival rate and the quality of life. Systemic therapy with radiolabeled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastatic NETs. In terms of tumour regression, the results obtained are encouraging.

The role of fine-needle aspiration performed with liquid-based cytology in the surgical management of thyroid lesions.

BACKGROUND: The aim of this retrospective study was to assess the accuracy and usefulness of cytological classification of fine-needle aspirates in determining the appropriate surgical treatment for thyroid lesions studied with conventional smears (CS) and liquid-based cytology (LBC) in a split-sample method. PATIENTS AND METHODS: A total of 353 patients were studied with both CS and LBC. The cytological diagnoses were classified according to the British Thyroid Association into 5 groups: Thy1, inadequate; Thy2, non-neoplastic or benign group including goiter, thyrocytic hyperplasia without nuclear atypia and thyroiditis; Thy3 or indeterminate/follicular proliferation, including follicular neoplasm not otherwise specified and oxyphilic follicular neoplasm; Thy4, suspicious for malignancy, including follicular lesion with nuclear pleomorphism; Thy5, diagnostic for malignancy including papillary carcinoma and medullary carcinoma. The efficacy of thyroid fine-needle aspiration processed by CS with LBC in a split-sample method was evaluated. RESULTS: Overall 164 patients were included in the Thy2, 97 in the Thy3, 49 in the Thy4, and 43 in the malignant Thy5 group. The percentage of unnecessary thyroidectomies decreased from 58.5 to 42% in our series. CONCLUSION: Our subclassification, according to the British Thyroid Association classification, attempts to reduce the number of Thy3 who undergo surgery. The comparison between the traditional management of thyroid lesions and our morphological categories with the use of CS and LBC together allows the number of unnecessary thyroidectomies to be reduced.

Reorganization of a Nuclear Medicine Department in Northern Italy During a 2-Month Lockdown for COVID-19 Pandemic.

Coronavirus disease (COVID-19) outbreak has profoundly changed the organization of hospital activities. We present our experience of reorganization of a nuclear medicine service settled in Northern Italy during the pandemic period of March and April 2020 characterized a government-mandated lockdown. Our service remained open during the whole period, performing approximately 80% of the routine practice, while maintaining it COVID-free despite the geographical context characterized by a high risk of infection. Reorganization involved all aspects of a nuclear medicine department, following local, national, and international guidelines for prioritizing patients, telephone and physical triages, deployment of appropriate personal protective equipment, social distancing, and logistic changes for scheduling examinations and disinfection procedures. All staff remained COVID-19-negative despite the unintentional admission of 4 patients who later turned out to be positive for the severe acute respiratory syndrome coronavirus 2. These adopted measures would serve as the basis for safe nuclear medicine services in the post-lockdown phase.