Head-to-head comparison between 18 F-DOPA PET/CT and 68 Ga-DOTA peptides PET/CT in detecting intestinal neuroendocrine tumours: A systematic review and meta-analysis.

PURPOSE: The imaging of intestinal neuroendocrine tumours (NETs) relies on functional positron emission tomography (PET) tracers; these tumours can be studied by means of both 68 Ga-DOTA peptides and 18 F-fluorodihydroxyphenyl- l-alanine (18 F-DOPA) PET/computed tomography (CT). As yet, it is unclear which of these two modalities offers the better sensitivity. We therefore conducted a meta-analysis to assess the available data. METHODS: PubMed, CENTRAL, Scopus and Web of Science were searched for studies comparing the sensitivity of 68 Ga-DOTA peptides and 18 F-DOPA PET/CT; papers up to February 2021 were considered. In each study, we considered sensitivity in terms of patient-based analysis (PBA), region-based analysis (RBA) and lesion-based analysis (LBA), and pooled the results yielded by each tracer. Multidisciplinary follow-up served as the standard of truth. RESULTS: Of the 636 records identified, 6 articles published between 2008 and 2021 were finally selected, and 112 intestinal NETs patients were included. The pooled sensitivity of 18 F-DOPA PET/CT was 83%, 89% and 95% on PBA, RBA and LBA, respectively. 68 Ga-DOTA peptides PET/CT showed sensitivity of 88%, 92% and 82% on PBA, RBA and LBA, respectively. No significant differences were found between the two tracers on PBA and RBA. By contrast, a clear trend towards significance in favour of 18 F-DOPA PET/CT was identified on LBA. The presence of a significant difference in favour of 18 F-DOPA PET/CT was confirmed in a subgroup analysis conducted only on the most recent and largest studies. In all three analyses, mild-to-high heterogeneity was found; however, no publication bias was observed. CONCLUSION: Both 18 F-DOPA PET/CT and 68 Ga-DOTA-peptides PET/CT are reliable diagnostic procedures in patients with intestinal NETs. However, in terms of lesion detection, a non-negligible difference in favour of 18 F-DOPA PET/CT was observed. Thus, the use of 18 F-DOPA PET/CT could be considered as a first-line molecular procedure in intestinal NETs.

How to better stratify the risk of differentiated thyroid carcinomas: the key role of radioactive iodine therapy, age, and gender.

PURPOSE: The risk of relapse of differentiated thyroid carcinomas (DTC) and their indication for radioactive iodine therapy (RAI) are assessed according to ATA risk stratification system principally based on tumor-nodes-metastasis (TNM) staging. However, while establishing the indication for RAI may be a "dilemma," performing it can improve the risk stratification. We aimed to evaluate whether (1) the stratification of risk of recurrence differs when TNM is considered with or without peri-RAI findings and (2) the assessment of the risk of disease-specific mortality is improved by adding age and gender. METHODS: From our database, all DTC patients treated with thyroidectomy and RAI from 1992 to 2017 were included. Subjects with a follow-up shorter than 1 year and positive thyroid antibodies were excluded. Patients were classified into (1) a three-category ATA model based on TNM (basic model) and (2) a five-category model based on TNM plus peri-RAI findings, i.e., thyroglobulin and 131I whole-body scan (advanced model). Relapse was proven by histology and/or imaging. Differences in disease-free survival (DFS) and overall survival (OS) were assessed. RESULTS: We enrolled 907 patients; of these, 4.4% died and 21% suffered recurrence. According to the basic model, there were 11.8% high-risk, 32.9% intermediate-risk, and 55.3% low-risk patients. According to the advanced model, 29.9% of patients were re-classified in a higher risk category and the five categories of this model displayed significantly different risks of relapse and death. The estimate of DFS was significantly higher in the advanced model than in the basic one (ΔC-index = + 6.8%, P < .001). By adding age and gender to the advanced model, the highest performance in predicting death was achieved (ΔC-index = + 5.1%, P < .001). CONCLUSIONS: The peri-RAI findings are essential in order to carefully stratify the risk of DTC recurrence. Integrating these data with age and gender enables those cases at highest risk of death to be identified.

The role of the deep convolutional neural network as an aid to interpreting brain [18F]DOPA PET/CT in the diagnosis of Parkinson's disease.

OBJECTIVES: To test the performance of a 3D convolutional neural network (CNN) in analysing brain [18F]DOPA PET/CT in order to identify patients with nigro-striatal neurodegeneration. We evaluated the robustness of the 3D CNN by testing it against a manual regional analysis of the striata by using a striatal-to-occipital ratio (SOR). METHODS: We analyzed patients who had undergone [18F]DOPA PET/CT from 2016 to 2018. Two examiners interpreted PET/CT images as positive or negative. Only patients with at least 2 years of follow-up and an ascertained neurological diagnosis were included. A 3D CNN was developed to evaluate [18F]DOPA PET/CT and refine the diagnosis of movement disorder. This system required training and testing, which were carried out on 2/3 and 1/3 of patients, respectively. A regional analysis was also conducted by drawing region of interest on T1-weighted 3D MRI scans, on which the [18F]DOPA PET images were first co-registered. RESULTS: Ninety-eight patients were enrolled: 43 presented nigro-striatal degeneration and 55 negative cases used as controls. After training on 69 patients, the diagnostic performance of the 3D CNN was then calculated in 29 patients. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy were 100%, 89%, 100%, 85% and 93%, respectively. When we compared the 3D CNN results with the SOR analysis, we found that the two patients falsely classified as positive by the 3D CNN procedure showed SOR values ≤ 5th percentile of the negative cases' distribution. CONCLUSIONS: 3D CNNs are able to interpret [18F]DOPA PET/CT properly, revealing patients affected by Parkinson's disease. KEY POINTS: • [18F]DOPA PET/CT is a sensitive diagnostic tool to identify patients with nigro-striatal neurodegeneration. • A semiquantitative evaluation of the images allows a more confident interpretation of the PET findings. • 3D convolutional neural network allows an accurate interpretation of 18F-DOPA PET/CT images, revealing patients affected by Parkinson's disease.

Radioiodine therapy of Graves' disease.

Graves' disease (GD), the most common cause of hyperthyroidism, is an autoimmune disease directly caused by circulating autoantibodies that bind and activate the TSH receptor, inducing metabolic activation of the thyroid gland; this may be associated with important cardiac (atrial fibrillation) and ocular (ophthalmopathy) complications. Treating GD with real curative intent implies the full elimination of the functioning thyroid parenchyma using surgery or radioactive iodine therapy (RAI). RAI has been used in humans with hyperthyroidism since 1941, thanks to the pioneering work of a physician (Dr. Saul Hertz) and a physicist (Dr. Arthur Roberts). The rationale of RAI is based on the effect of radiation of 131I on target cells leading to DNA damage, both directly, through breakage of molecular bonds, and indirectly through the formation of free radicals. In particular, irradiation causes a broad spectrum of cellular damage due to the production of reactive oxygen species and lipid peroxidation of the plasma membrane. Thus, RAI-related cellular death takes place through both apoptosis and necrosis. The aim of this review was to summarize indications, efficacy, safety profile, and dosimetric aspects of RAI treatment in patients affected by GD.

To Enhance or Not to Enhance? The Role of Contrast Medium 18F-FDG PET/CT in Recurrent Ovarian Carcinomas.

Background and Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography/X-ray computed tomography (PET/CT) represents the mainstay diagnostic procedure for suspected ovarian cancer (OC) recurrence. PET/CT can be integrated with contrast medium and in various diagnostic settings; however, the effective benefit of this procedure is still debated. We aimed to compare the diagnostic capabilities of low-dose and contrast-enhanced PET/CT (PET/ldCT and PET/ceCT) in patients with suspected ovarian cancer relapse. Materials and Methods: 122 OC patients underwent both PET/ldCT and PET/ceCT. Two groups of nuclear medicine physicians and radiologists scored the findings as positive or negative. Clinical/radiological follow-up was used as ground truth. Sensitivity, specificity, negative/positive predictive value, and accuracy were calculated at the patient and the lesion level. Results: A total of 455 and 474 lesions were identified at PET/ldCT and PET/ceCT, respectively. At the lesion level, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were not significantly different between PET/ldCT and PET/ceCT (98%, 93.3%, 97.4%, 94.9%, and 96.9% for PET/ldCT; 99%, 95.5%, 98.3%, 97%, and 98% for PET/ceCT, p = ns). At the patient level, no significant differences in these parameters were identified (e.g., p = 0.22 and p = 0.35 for accuracy, in the peritoneum and lymph nodes, respectively). Smaller peritoneal/lymph node lesions close to physiological FDG uptake sources were found in the cases of misidentification by PET/ldCT. PET/ceCT prompted a change in clinical management in four cases (3.2%) compared to PET/ldCT. Conclusions: PET/ceCT does not perform better than PET/ldCT but can occasionally clarify doubtful peritoneal findings on PET/ldCT. To avoid unnecessary dose to the patient, PET/ceCT should be excluded in selected cases.

Copper, PET/CT and prostate cancer: a systematic review of the literature.

Copper is an essential element that plays an important role in both cancer development and growth. Indeed, high levels of copper have been found in prostate cancer (PCa), and this finding have paved the way for the use of this element as a target for positron emission tomography (PET) imaging. Copper64 (64Cu) can be used alone, as 64CuCl2, and also as a precursor for the in-vitro radio-labelling of specific carriers for PET imaging in PCa, (e.g. associated to prostate-specific membrane antigen: PSMA). The use of 64Cu-PSMA can yield late acquisitions in which PET images are characterized by a higher target-to-background ratio. At the same time, the shorter positron range of 64Cu provides high spatial resolution, which leads to better detection of small lesions. In this context, the aim of this review was to systematically review studies evaluating the identification of PCa in humans by means of 64CuCl2 and other PET tracers radio-labelled with 64Cu.

Role of 64CuCl2 PET/CT in Detecting and Staging Muscle-Invasive Bladder Cancer: Comparison with Contrast-Enhanced CT and 18F-FDG PET/CT.

Molecular imaging of muscle-invasive bladder cancer (MBC) is restricted to its locoregional and distant metastases, since most radiopharmaceuticals have a urinary excretion that limits the visualization of the primary tumor. 64CuCl2 , a positron-emitting radiotracer with nearly exclusive biliary elimination, could be well suited to exploring urinary tract neoplasms. In this study, we evaluated the feasibility of 64CuCl2-based staging of patients with MBC; furthermore, we compared the diagnostic capability of this method with those of the current gold standards, that is, contrast-enhanced CT (ceCT) and 18F-FDG PET/CT. Methods: We prospectively enrolled patients referred to our institution for pathology-confirmed MBC staging/restaging between September 2021 and January 2023. All patients underwent ceCT, 18F-FDG, and 64CuCl2 PET/CT within 2 wk. Patient-based analysis and lesion-based analysis were performed for all of the potentially affected districts (overall, bladder wall, lymph nodes, skeleton, liver, lung, and pelvic soft tissue). Results: Forty-two patients (9 women) were enrolled. Thirty-six (86%) had evidence of disease, with a total of 353 disease sites. On patient-based analysis, ceCT and 64CuCl2 PET/CT showed higher sensitivity than 18F-FDG PET/CT in detecting the primary tumor (P < 0.001); moreover, 64CuCl2 PET/CT was slightly more sensitive than 18F-FDG PET/CT in disclosing soft-tissue lesions (P < 0.05). Both PET methods were more specific and accurate than ceCT in classifying nodal lesions (P < 0.05). On lesion-based analysis, 64CuCl2 PET/CT outperformed 18F-FDG PET/CT and ceCT in detecting disease localizations overall (P < 0.001), in the lymph nodes (P < 0.01), in the skeleton (P < 0.001), and in the soft tissue (P < 0.05). Conclusion: 64CuCl2 PET/CT appears to be a sensitive modality for staging/restaging of MBC and might represent a "one-stop shop" diagnostic method in these scenarios.

Diagnostic and Dosimetry Features of [64Cu]CuCl2 in High-Grade Paediatric Infiltrative Gliomas.

PURPOSE OF THE REPORT: Paediatric diffuse high-grade gliomas (PDHGG) are rare central nervous system neoplasms lacking effective therapeutic options. Molecular imaging of tumour metabolism might identify novel diagnostic/therapeutic targets. In this study, we evaluated the distribution and the dosimetry aspects of [64Cu]CuCl2 in PDHGG subjects, as copper is a key element in cellular metabolism whose turnover may be increased in tumour cells. MATERIAL AND METHODS: Paediatric patients with PDHGG were prospectively recruited. [64Cu]CuCl2 PET/CT was performed 1 h after tracer injection; if the scan was positive, it was repeated 24 and 72 h later. Lesion standardised uptake value (SUV) and target-to-background ratio (TBR) were calculated. Tumour and organ dosimetry were computed using the MIRD algorithm. Each patient underwent an MRI scan, including FLAIR, T2-weighted and post-contrast T1-weighted imaging. RESULTS: Ten patients were enrolled (median age 9, range 6-16 years, 6 females). Diagnoses were diffuse midline gliomas (n = 8, 5 of which with H3K27 alterations) and diffuse hemispheric gliomas (n = 2). Six patients had visible tracer uptake (SUV: 1.0 ± 0.6 TBR: 5 ± 3.1). [64Cu]CuCl2 accumulation was always concordant with MRI contrast enhancement and was higher in the presence of radiological signs of necrosis. SUV and TBR progressively increased on the 24- and 72-h acquisitions (p < 0.05 and p < 0.01, respectively). The liver and the abdominal organs received the highest non-target dose. CONCLUSIONS: [64Cu]CuCl2 is a well-tolerated radiotracer with reasonably favourable dosimetric properties, showing selective uptake in tumour areas with visible contrast enhancement and necrosis, thus suggesting that blood-brain barrier damage is a pre-requisite for its distribution to the intracranial structures. Moreover, tracer uptake showed an accumulating trend over time. These characteristics could deserve further analysis, to determine whether this radiopharmaceutical might have a possible therapeutic role as well.

Head-to-head comparison among 18F-choline PET/CT, 4D contrast-enhanced CT, and 18F-choline PET/4D contrast-enhanced CT in the detection of hyperfunctioning parathyroid glands: a systematic review and meta-analysis.

INTRODUCTION: In primary hyperparathyroidism (PHPT), the localization of hyperfunctioning parathyroid gland (HPTG) allows tailored surgery. Although Four-Dimensional Contrast-enhanced Computed Tomography (4DCeCT) and 18F-choline Positron Emission Tomography/Computed Tomography (PET/CT) are reported to be promising second-line imaging procedures, no meta-analysis of their comparison exists. DESIGN: we conducted a systematic review and meta-analysis to find original papers reporting the head-to-head comparison of 4DCeCT, 18F-choline PET/CT and integrated 18F-choline-PET/4DCeCT. METHODS: this systematic review was conducted according to PRISMA. PubMed, CENTRAL, Scopus, and Web of Science were searched until January 2021. Studies comparing the ability of 4DCeCT, 18F-choline PET/CT and 18F-choline PET/4DCeCT to identify HPTG in patients with PHPT were selected. A per patient-based analysis of the three procedures was conducted in all patients (detection rate, DR) and in those with histologically confirmed HPTG (sensitivity). RESULTS: Of the 78 records identified, five articles (153 PHPT patients) published between January the 1st, 2018 and January the 31st, 2021 were included. The pooled DR of 18F-choline PET/CT, 4DCeCT and 18F-choline PET/4DCeCT was 0.86, 0.69, and 0.86, respectively, while their pooled sensitivity was 0.89, 0.77 and 0.93, respectively. The analysis of pooled discrepancy showed that the sensitivity of 18F-choline PET/CT and 18F-choline PET/4DCeCT was higher than that of 4DCeCT by 0.11 and 0.13, respectively, the sensitivity of 18F-choline PET/4DCeCT being 0.06 higher than that of 18F-Choline PET/CT. CONCLUSIONS: This meta-analysis suggests that the sensitivity of 18F-choline PET/CT and 18F-choline PET/4DCeCT is higher than that of 4DCeCT, while only a slight difference was observed between 18F-choline PET/CT and 18F-choline PET/4DCeCT.

A Three-Domain Scoring System to Customize the Risk of Relapse of Differentiated Thyroid Carcinoma.

PURPOSE: the validation of a new scoring model considering the principal risk factors of differentiated thyroid cancer (DTC) relapse. METHODS: we evaluated all DTC patients treated with thyroidectomy and radioactive iodine (RAI) therapy. Three domains were considered: the demographic domain (age and gender), the surgical domain (histology and the American Thyroid Association risk categories), and the RAI-related domain (pre-RAI thyroglobulin and post-therapeutic 131I whole-body scan). The progression-free survival was assessed. The patients' sample was randomly split into a training and validation set. The three-domain score was calculated as the weighted sum of the levels of each significant factor, then scaled to an integer range (0-100) and, finally, stratified into terciles: mild risk 0-33, moderate risk 34-66, and severe risk 67-100. RESULTS: 907 DTC patients were included. The RAI-related domain was the most relevant factor in the score calculation. The tercile stratification identified significantly different survival curves: patients within the two upper terciles showed approximately 6 to 30 times more progressive risk than patients at mild risk. CONCLUSION: we have validated a three-domain scoring system and the principal impact on this score is provided by the peri-RAI findings, whose prognostic role seems to be essential in risk identification.

Predictors of poor seroconversion and adverse events to SARS-CoV-2 mRNA BNT162b2 vaccine in cancer patients on active treatment.

PURPOSE: Initial findings in patients with cancer suggest a lower seroconversion to SARS-CoV-2 vaccination possibly related to myelo-immunosuppressive therapies. We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunisation (AEFI) to the BNT162b2 vaccine in patients on active treatment. PATIENTS AND METHODS: Cancer patients, candidates to two doses of BNT162b2 SARS-CoV-2 vaccination, were enrolled. Patients on active surveillance served as controls. The primary endpoint was poor seroconversion (anti S1/S2 IgG < 25 AU/mL) after 21 days from the second dose. RESULTS: Between March and July 2021, 320 subjects were recruited, and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immune-checkpoint-inhibitors (ICI). Compared to controls, the risk of no IgG response was greater for chemotherapy (p = 0.033), targeted therapy (0.005) and hormonotherapy (p = 0.051). Lymphocyte count < 1 × 109/L (p = 0.04) and older age (p = 0.03) also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (p = 0.001) and younger patients (p = 0.009). CONCLUSION: Chemotherapy, targeted therapy, hormone therapy, lymphocyte count < 1 × 109/L, and increasing age predict poor seroconversion after two doses of BNT162b2 in up to 20% of patients, indicating the need for a third dose and long-term serological testing in non-responders. AEFI occur much more frequently in women and younger subjects who may benefit from preventive medications. CLINICALTRIALS. GOV IDENTIFIER: NCT04932863.

Diagnosis, Treatment Response, and Prognosis: The Role of 18F-DOPA PET/CT in Children Affected by Neuroblastoma in Comparison with 123I-mIBG Scan: The First Prospective Study.

Our purpose was to evaluate the diagnostic role of 18F-3,4-dihydroxyphenylalanine (DOPA) PET/CT at the time of staging in children with neuroblastoma and to investigate its ability to assess treatment response. We also investigated the prognostic value of 18F-DOPA PET/CT at the same time points. Methods: We enrolled children with neuroblastoma at onset. Before and after induction chemotherapy, all patients underwent 18F-DOPA PET/CT and 123I-metaiodobenzylguanidine (MIBG) scanning plus SPECT/CT. 18F-DOPA PET/CT results were compared with those of 123I-MIBG whole-body scanning (WBS). For each modality, patient-based analysis and lesion-based analysis were performed and sensitivity was calculated. We applied scoring systems to 123I-MIBG scanning and 18F-DOPA PET/CT (i.e.,123I-MIBG WBS score and whole-body metabolic burden [WBMB], respectively) and evaluated the association between these parameters, the principal neuroblastoma risk factors, and outcome. Results: We enrolled 16 high-risk and 2 intermediate-risk neuroblastoma patients. On patient-based analysis, sensitivity in detecting primary tumors, soft-tissue metastases, and bone or bone-marrow metastases was 83%, 50%, and 92%, respectively, for 123I-MIBG WBS versus 94%, 92%, and 100%, respectively, for 18F-DOPA PET/CT. On lesion-based analysis, the sensitivity of 18F-DOPA PET/CT in detecting soft-tissue and bone or bone-marrow metastases was 86% and 99%, respectively-significantly higher than that of 123I-MIBG WBS, at 41% and 93%, respectively. After therapy, on patient-based analysis, the sensitivity in detecting primary tumors, soft-tissue metastases, and bone or bone-marrow metastases was 72%, 33%, and 38%, respectively, for 123I-MIBG WBS versus 83%, 75% and 54%, respectively, for 18F-DOPA PET/CT. On lesion-based analysis, the sensitivity of 18F-DOPA PET/CT in detecting soft-tissue and bone or bone-marrow metastases was 77% and 86%, respectively-significantly higher than that of 123I-MIBG WBS, at 28% and 69%, respectively. During follow-up, 8 cases of disease progression and 5 deaths occurred. On multivariate analysis, only posttherapeutic 18F-DOPA WBMB (>7.5) was associated with progression-free survival. Conclusion:18F-DOPA PET/CT is more sensitive than 123I-MIBG WBS in staging neuroblastoma patients and evaluating disease persistence after chemotherapy. In a time-to-event analysis, posttherapeutic 18F-DOPA WBMB remained the only risk factor associated with disease progression.

Diagnostic value of retrospectively fused 64CuCl2 PET/MRI in biochemical relapse of prostate cancer: comparison with fused 18F-Choline PET/MRI, 64CuCl2 PET/CT, 18F-Choline PET/CT, and mpMRI.

PURPOSE: To assess the diagnostic value of retrospectively fused PET/MRI by comparing the detection rates (DRs) of fused 64CuCl2 PET/MRI vs. fused 18F-Choline PET/MRI in patients with suspected prostatic cancer (PCa) recurrence. The secondary objective was to compare the DRs of fused PET/MRI vs. those of the separate imaging modalities. METHODS: We retrospectively evaluated 50 PCa patients with biochemical relapse after radical prostatectomy (RP) or radiotherapy (RT). All patients underwent 64CuCl2 PET/CT, 18F-Choline PET/CT, and multiparametric magnetic resonance imaging (mpMRI) within 15 days. Fused 64CuCl2-PET/MRI and fused 18F-Choline PET/MRI images were obtained by retrospective co-registration of MRI and PET images. Experienced readers interpreted the images, and the DRs of each imaging modality were assessed. RESULTS: In the patient-based analysis, overall DRs of fused 64CuCl2 PET/MRI, fused 18F-Choline PET/MRI, 64CuCl2 PET/CT, 18F-Choline PET/CT, and mpMRI were 88%, 68%, 82%, 56%, and 74%, respectively. In the lesion-based analysis, overall DRs of fused 64CuCl2 PET/MRI, fused 18F-Choline PET/MRI, 64CuCl2 PET/CT, 18 F-Choline PET/CT, and mpMRI were 95%, 66%, 87%, 58%, and 71%, respectively. CONCLUSIONS: Retrospectively fused PET/MRI is able to overcome the limitations of the separate interpretation of the individual imaging modalities. Fused 64CuCl2 PET/MRI provided the highest diagnostic performance in the detection of PCa local relapse.

Indeterminate thyroid nodules. The role of 18F-FDG PET/CT in the "era" of ultrasonography risk stratification systems and new thyroid cytology classifications.

PURPOSE: To evaluate the reliability of 18F-FDG PET/CT in distinguishing differentiated thyroid cancers (DTCs) and follicular neoplasms (FNs) from nodular hyperplasias (NH) in thyroid nodules with indeterminate cytology according to the Italian consensus for the classification and reporting of thyroid cytology (ICCRTC). We also tested whether the 18F-FDG PET/CT result was an independent risk factor for DTCs or FNs when sex, age, nodule dimensions, the European Thyroid Imaging and Reporting Data System (EU-TIRADS) and ICCRTC were considered. METHODS: We evaluated all patients with thyroid nodules and indeterminate cytology from September 2015 to May 2019; nodules were classified as low risk (TIR3A) and high risk (TIR3B) according to the ICCRTC. Neck ultrasonography features according to EU-TIRADS were re-evaluated and 18F-FDG PET/CT performed. All these patients were surgically treated. RESULTS: We included 111 patients; 67 nodules were classified as TIR3A and 44 as TIR3B. Overall, we found 27 DTCs, 57 NHs and 27 FNs. Among 73 FDG-negative nodules, we found four low-risk papillary thyroid cancers. All follicular thyroid cancers were identified by 18F-FDG-PET/CT. All TIR3A with low-risk US and negative 18F-FDG-PET/CT were NH. In TIR3A nodules, the sensitivity, specificity, negative and positive predictive values (NPV, PPV) of 18F-FDG PET/CT and EU-TIRADS for DTCs were 77.8%, 41.4%, 92.3%, 17.1% and 66.7%, 56.9%, 91.7%, 19.4%, respectively. In TIR3B nodules, the sensitivity, specificity, NPV and PPV of 18F-FDG PET/CT and EU-TIRADS for DTCs were 88.9%, 38.5%, 83.3%, 50% and 88.2%, 58.3%, 87.5%, 60%, respectively. On multivariate analysis, 18F-FDG-PET/CT (OR 9.04), ICCRTC (O.R. 7.57) and EU-TIRADS (OR 4.41) were all independent risk factors associated to DTCs and FNs. CONCLUSION: 18F-FDG-PET/CT is a reliable rule-out test for DTC even in thyroid nodules with indeterminate high-risk results. In this subgroup, PPV also tends to be considerable. 18F-FDG-PET/CT results, ICCRTC and EU-TIRADS proved independent risk factors associated to DTCs and FNs.

Biokinetic and dosimetric aspects of 64CuCl2 in human prostate cancer: possible theranostic implications.

BACKGROUND: The aim of the present study is to evaluate the kinetics and dosimetry of 64CuCl2 in human prostate cancer (PCa) lesions. We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external beam radiation therapy. All patients underwent 64CuCl2-PET/CT to detect PCa recurrence/metastases. Volumes of interest were manually drawn for each 64CuCl2 avid PCa lesion with a diameter > 1 cm on mpMRI in each patient. Time-activity curves for all lesions were obtained. The effective and biological half-life and the standard uptake values (SUVs) were calculated. Tumour/background ratio (TBR) curves as a function of time were considered. Finally, the absorbed dose per lesion was estimated. RESULTS: The mean effective half-life of 64CuCl2 calculated in the lymph nodes (10.2 ± 1.7 h) was significantly higher than in local relapses (8.8 ± 1.1 h) and similar to that seen in bone metastases (9.0 ± 0.4 h). The mean 64CuCl2 SUVmax calculated 1 h after tracer injection was significantly higher in the lymph nodes (6.8 ± 4.3) and bone metastases (6.8 ± 2.9) than in local relapses (4.7 ± 2.4). TBR mean curve of 64CuCl2 revealed that the calculated TBRmax value was 5.0, 7.0, and 6.2 in local relapse and lymph node and bone metastases, respectively, and it was achieved about 1 h after 64CuCl2 injection. The mean absorbed dose of the PCa lesions per administrated activity was 6.00E-2 ± 4.74E-2mGy/MBq. Indeed, for an administered activity of 3.7 GBq, the mean dose absorbed by the lesion would be 0.22 Gy. CONCLUSIONS: Dosimetry showed that the dose absorbed by PCa recurrences/metastases per administrated activity was low. The dosimetric study performed does not take into account the possible therapeutic effect of the Auger electrons. Clinical trials are needed to evaluate 64Cu internalization in the cell nucleus that seems related to the therapeutic effectiveness reported in preclinical studies.