Tumor Burden of Iodine-Avid Bone Metastatic Thyroid Cancer Identified via 18F-Sodium Fluoride PET/CT Imaging.

BACKGROUND: Patients with differentiated thyroid cancer (DTC) are referred to radioactive 131I (RAI) therapy and post-therapy 131I whole-body scintigraphy (WBS) to identify local and/or remote metastases. Positron emission tomography (PET)/computed tomography (CT) imaging with 18F-fluoro-D-glucose (FDG) or 18F-sodium fluoride (NaF) may also be used with these patients for the evaluation of bone metastases. We compared the role of 18F-NaF PET/CT and 18F-FDG-PET/CT in patients with DTC and documented bone metastases at post-therapy WBS. METHODS: Ten consecutive DTC patients with iodine avid bone metastasis at post-therapy WBS referred to 18F-NaF PET/CT and 18F-FDG PET/CT were studied. The findings of the three imaging procedures were compared for abnormal detection rates and concordance. RESULTS: At post-therapy 131I WBS, all patients had skeletal involvement with a total of 21 bone iodine avid lesions. At 18F-FDG PET/TC, 19 bone lesions demonstrated increased tracer uptake and CT pathological alterations, while 2 lesions did not show any pathological finding. At 18F-NaF PET/CT, the 19 bone lesions detected at 18F-FDG PET/TC also demonstrated abnormal tracer uptake, and the other 2 bone iodine avid foci did not show any pathological finding. CONCLUSIONS: In patients with DTC, 18F-NaF PET/CT did not obtain more information on the metastatic skeletal involvement than post-therapy 131I WBS and 18F-FDG PET/CT.

Thyroid Cancer Radiomics: Navigating Challenges in a Developing Landscape.

In a review from 2021 by Cao et al [...].

Emerging Role of Nuclear Medicine in Prostate Cancer: Current State and Future Perspectives.

Prostate cancer is the most frequent epithelial neoplasia after skin cancer in men starting from 50 years and prostate-specific antigen (PSA) dosage can be used as an early screening tool. Prostate cancer imaging includes several radiological modalities, ranging from ultrasonography, computed tomography (CT), and magnetic resonance to nuclear medicine hybrid techniques such as single-photon emission computed tomography (SPECT)/CT and positron emission tomography (PET)/CT. Innovation in radiopharmaceutical compounds has introduced specific tracers with diagnostic and therapeutic indications, opening the horizons to targeted and very effective clinical care for patients with prostate cancer. The aim of the present review is to illustrate the current knowledge and future perspectives of nuclear medicine, including stand-alone diagnostic techniques and theragnostic approaches, in the clinical management of patients with prostate cancer from initial staging to advanced disease.

Efficacy of Empirical Radioiodine Therapy in Patients with Differentiated Thyroid Cancer and Elevated Serum Thyroglobulin without Evidence of Structural Disease: A Propensity Score Analysis.

We assessed the outcome of administration of empiric radioactive iodine (RAI) therapy to patients with differentiated thyroid cancer (DTC), in a propensity-score-matched cohort of patients with biochemical incomplete response (BIR) and without evidence of structural disease. We retrospectively evaluated 820 DTC patients without distant metastases, who underwent total thyroidectomy followed by RAI therapy, with available BIR at 12 months and follow-up evaluations. The patients were categorized according to the administration of empiric therapy (ET). To account for differences between patients with (n = 119) and without (n = 701) ET, a propensity-score-matched cohort of 119 ET and 119 no-ET patients was created. The need for additional therapy and the occurrence of structural disease were considered as end-points. During a median follow-up of 53 months (range 3-285), 57 events occurred (24% cumulative event rate). The rate of events was significantly higher in the no-ET compared to the ET patients (30% vs. 18% p < 0.001). The multivariate Cox analysis identified age (p < 0.01), pre-therapy Tg (p < 0.05) and empiric RAI therapy (p < 0.01) as predictors of outcome. The Kaplan-Meier analysis found that progression-free survival was lower in no-ET patients compared to the ET group (p < 0.01). In patients with DTC treated with surgery and RAI, and with biochemical incomplete response at the 12-month evaluation, their prognosis seemed to be affected by Tg values and the empiric treatment. The identification of candidates for this approach may improve prognosis.

Prediction of 2-[18F]FDG PET-CT SUVmax for Adrenal Mass Characterization: A CT Radiomics Feasibility Study.

BACKGROUND: Indeterminate adrenal masses (AM) pose a diagnostic challenge, and 2-[18F]FDG PET-CT serves as a problem-solving tool. Aim of this study was to investigate whether CT radiomics features could be used to predict the 2-[18F]FDG SUVmax of AM. METHODS: Patients with AM on 2-[18F]FDG PET-CT scan were grouped based on iodine contrast injection as CT contrast-enhanced (CE) or CT unenhanced (NCE). Two-dimensional segmentations of AM were manually obtained by multiple operators on CT images. Image resampling and discretization (bin number = 16) were performed. 919 features were calculated using PyRadiomics. After scaling, unstable, redundant, and low variance features were discarded. Using linear regression and the Uniform Manifold Approximation and Projection technique, a CT radiomics synthetic value (RadSV) was obtained. The correlation between CT RadSV and 2-[18F]FDG SUVmax was assessed with Pearson test. RESULTS: A total of 725 patients underwent PET-CT from April 2020 to April 2021. In 150 (21%) patients, a total of 179 AM (29 bilateral) were detected. Group CE consisted of 84 patients with 108 AM (size = 18.1 ± 4.9 mm) and Group NCE of 66 patients with 71 AM (size = 18.5 ± 3.8 mm). In both groups, 39 features were selected. No statisticallyf significant correlation between CT RadSV and 2-[18F]FDG SUVmax was found (Group CE, r = 0.18 and p = 0.058; Group NCE, r = 0.13 and p = 0.27). CONCLUSIONS: It might not be feasible to predict 2-[18F]FDG SUVmax of AM using CT RadSV. Its role as a problem-solving tool for indeterminate AM remains fundamental.

Diagnosis, Management and Theragnostic Approach of Gastro-Entero-Pancreatic Neuroendocrine Neoplasms.

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) constitute an ideal target for radiolabeled somatostatin analogs. The theragnostic approach is able to combine diagnosis and therapy by the identification of a molecular target that can be diagnosed and treated with the same radiolabeled compound. During the last years, advances in functional imaging with the introduction of somatostatin analogs and peptide receptor radionuclide therapy, have improved the diagnosis and treatment of GEP-NENs. Moreover, PET/CT imaging with 18F-FDG represents a complementary tool for prognostic evaluation of patients with GEP-NENs. In the field of personalized medicine, the theragnostic approach has emerged as a promising tool in diagnosis and management of patients with GEP-NENs. The aim of this review is to summarize the current evidence on diagnosis and management of patients with GEP-NENs, focusing on the theragnostic approach.

Prognostic value of 12-month response to therapy in pediatric patients with differentiated thyroid cancer.

PURPOSE: In pediatric patients with differentiated thyroid cancer (DTC) we assessed the prognostic value of the 12-month response to therapy after initial treatment with surgery and radioactive iodine (RAI). METHODS: We retrospectively evaluated 94 pediatric patients with DTC, treated with surgery and RAI who were initially classified as low, intermediate or high risk of relapse of disease according to the American Thyroid Association (ATA) guidelines. Twelve months after RAI administration the response to therapy was assessed by serum thyroglobulin (Tg) measurement and neck ultrasound and patients were classified as having excellent response (ER) or no-ER. RESULTS: At the 12 months evaluation, 62 (66%) patients had ER and 32 (34%) no-ER. During a mean follow-up time of 86 months (range 9-517), 19 events occurred (20% cumulative event rate). Events occurred more frequently in younger patients (p < 0.05), in those at ATA intermediate/high risk (p < 0.01) and with a pre-RAI therapy Tg level > 10 ng/mL (p < 0.001), and in those with no-ER (p < 0.001). At multivariate analysis, the evidence of no-ER was the only independent predictor of events. CONCLUSION: In pediatric patients with DTC, the response to therapy evaluated 12 months after initial treatment has an independent prognostic impact and is able to predict mid-term outcome. Patients with no-ER at 12 months after RAI therapy should be closely followed-up.

Type 2 Deiodinase Thr92Ala Polymorphism and Aging Are Associated with a Decreased Pituitary Sensitivity to Thyroid Hormone.

Background: The DIO2 Thr92Ala polymorphism (rs225014), which occurs in about 15-30% of Caucasian people, determines a less efficient type 2 deiodinase (D2) enzyme. The aim of this study was to determine the impact of DIO2 Thr92Ala polymorphism on the serum thyrotropin (TSH) levels in thyroidectomized patients with hypothyroidism and to evaluate whether TSH levels and aging could be related, at pituitary level, to D2 activity. Methods: This prospective study was performed on 145 thyroid cancer patients, treated with total thyroidectomy, and undergoing radioiodine treatment after 3 weeks of levothyroxine (LT4) withdrawal. A mouse model has been used to determine D2 protein and mRNA levels in pituitary during aging. Results: Genetic analysis identified DIO2 Thr92Ala polymorphism in 56% of participants: 64/145 (44%) patients were homozygous wild type (WT) (Thr/Thr), 64 (44%) heterozygous (Thr/Ala), and 17 (12%) homozygous mutant (Ala/Ala). A significant negative relationship was observed between aging and the rise in serum TSH levels during LT4 withdrawal. However, this negative correlation found in WT was reduced in heterozygous and lost in mutant homozygous patients (Thr/Thr r = -0.45, p = 0.0002, 95% confidence interval [CI] -0.63 to -0.23; Ala/Thr r = -0.39, p = 0.0012, CI -0.60 to -0.67; and Ala/Ala r = -0.30, p = 0.2347; CI -0.70 to 0.20). Accordingly, when we compared the TSH measured in each patient to its theoretical value predicted from age, the TSH did not reach its putative target in 47% of WT patients, in 70% of Ala/Thr, and 76% of Ala/Ala carrying patients (p = 0.0036). This difference was lost in individuals older than 60 years, suggesting a decline of D2 associated with aging. The hypothesis that the pituitary D2 decreases with age was confirmed by the evidence that D2 mRNA and protein levels were lower in pituitary from old versus young mice. Conclusion: An age-related decline in TSH production in response to hypothyroidism was correlated with decreased D2 levels in pituitary. The presence of DIO2 homozygous Ala/Ala polymorphism was associated with a reduced level of TSH secretion in response to hypothyroidism, indicating a decreased pituitary sensitivity to serum thyroxine variation (Institutional Research Ethics board approval number no. 433/21).

Hyperfunctioning parathyroid gland and skeletal involvement on [18F]fluorocholine PET/CT: one look with two views.

Hyperparathyroidism is an endocrine disorder that may be associated with other metabolic diseases. Non-invasive imaging techniques including [99mTc]Tc-sestamibi single-photon emission computed tomography (SPECT) and [18F]fluorocholine positron emission tomography (PET)/computed tomography (CT) play a key role on management of patients with hyperparathyroidism. We report for the first time a case of a patient with evidence of both hyperfunctioning parathyroid tissue and multiple lytic bone lesions on [18F]fluorocholine PET/CT imaging. The present case report highlights the potential role of whole-body [18F]fluorocholine PET/CT for the identification of both parathyroid adenoma and multiple bone lesions in a single diagnostic setting.

Initial Testing of an Approximated, Fast Calculation Procedure for Personalized Dosimetry in Radionuclide Therapy Based on Planar Whole-Body Scan and Monte-Carlo Specific Dose Rates from the OpenDose Project.

Individualized dosimetry in nuclear medicine is currently at least advisable in order to obtain the best risk-benefit balance in terms of the maximal dose to lesions and under-threshold doses to radiosensitive organs. This article aims to propose a procedure for fast dosimetric calculations based on planar whole-body scintigraphy (WBS) images and developed to be employed in everyday clinical practice. METHODS: For simplicity and legacy reasons, the method is based on planar imaging dosimetry, complemented with some assumptions on the radiopharmaceutical kinetics empirically derived from single-photon emission tomography/computed tomography (SPECT/CT) image analysis. The idea is to exploit a rough estimate of the time-integrated activity as has been suggested for SPECT/CT dosimetry but using planar images. The resulting further reduction in dose estimation accuracy is moderated by the use of a high-precision Monte-Carlo S-factor, such as those available within the OpenDose project. RESULTS: We moved the problem of individualized dosimetry to a transformed space where comparing doses was imparted to the ICRP Average Male/Female computational phantom, resulting from an activity distribution related to patient's pharmaceutical uptake. This is a fast method for the personalized dosimetric evaluation of radionuclide therapy, bearing in mind that the resulting doses are meaningful in comparison with thresholds calculated in the same framework. CONCLUSION: The simplified scheme proposed here can help the community, or even the single physician, establish a quantitative guide-for-the-eye approach to individualized dosimetry.

Prognostic Value of Hybrid PET/MR Imaging in Patients with Differentiated Thyroid Cancer.

Background: Hybrid positron emission tomography (PET)/magnetic resonance (MR) is an emerging imaging modality with great potential to provide complementary data acquired at the same time, under the same physiological conditions. The aim of this study was to evaluate the prognostic value of hybrid 18F-fluorodeoxyglucose (FDG) PET/MR in patients with differentiated thyroid cancer (DTC) who underwent total thyroidectomy and radioactive iodine therapy for suspicion of disease relapse. Methods: Between November 2015 and February 2017, 55 patients underwent hybrid 18F-FDG PET/MR. Assessment of positive MR was made considering all sequences in terms of malignancy based on the morphological T2-weighted features and the presence of restricted diffusivity on diffusion-weighted imaging images and both needed to be positive on the same lesion. Both foci with abnormal 18F-FDG uptake, which corresponded to tissue abnormalities on the MR, and tracer accumulation, which did not correspond to normal morphological structures, were considered positive. Results: During follow-up (mean 42 ± 27 months), 29 patients (53%) had disease recurrence. In the Cox univariate regression analysis age, serum Tg level ≥ 2 ng/mL, positive short tau inversion recovery (STIR), and positive PET were significant predictors of DTC recurrence. Kaplan−Meier survival analyses showed that patients with Tg ≥ 2 ng/mL had poorer outcomes compared to those with serum Tg level < 2 ng/mL (p < 0.05). Similarly, patients with positive STIR and positive PET had a worst outcome compared to those with negative STIR (p < 0.05) and negative PET (p < 0.005). Survival analysis performed in the subgroup of 36 subjects with Tg level ≥ 2 ng/mL revealed that patients with positive PET had a worst outcome compared to those with negative PET (p < 0.05). Conclusions: Age, serum Tg level ≥ 2 ng/mL, positive STIR, and positive 18F-FDG PET were significant predictors of DTC recurrence. However, the serum Tg level was the only independent predictor of DTC. Hybrid PET/MR imaging may have the potential to improve the information content of one modality with the other and would offer new opportunities in patients with DTC. Thus, further studies in a larger patient population are needed to understand the additional value of 18F-FDG PET/MR in patients with DTC.