Distribution of Functional Status of Thyroid Nodules and Malignancy Rates of Hyperfunctioning and Hypofunctioning Thyroid Nodules in Germany.

AIM: Thyroid scintigraphy enables the depiction of the functional status of thyroid nodules (TNs) with both, 99mTc-pertechnetate and 123Iodine. The functional status is relevant for diagnostic procedures for the differentiation of benign and malignant TNs. The aim of this study was to examine the current frequencies of hyper-, hypo- and isofunctioning TNs in Germany and to estimate the risk of malignancy with regard to functional status. METHODS: In 11 study centers, a minimum of 100 nodules per center were consecutively enrolled between July 2019 and April 2020. Inclusion criteria were: newly diagnosed nodule, nodule' size of 10 mm or more, thyroid scintigraphy. Exclusion criteria were: completely cystic TNs, patients with prior radioiodine therapy or thyroid surgery. The risk of malignancy was estimated for hyper- and hypofunctioning TNs. RESULTS: Overall, 849 patients (72 % women) with 1262 TNs were included. Patients' age ranged from 18 to 90 years. Most TNs were hypofunctioning (n=535, 42%) followed by isofunctioning TNs (n=488, 39%) and hyperfunctioning TNs (n=239, 19%). When only TNs with a maximum size of 2 cm or more were considered the rate of hyperfunctioning and hypofunctioning TNs increased (to 27% and 49%) while isofunctioning TNs decreased. Only one of all hyperfunctioning TNs was malignant. In hypofunctioning nodules, the malignancy rate was estimated at 10%. CONCLUSION: In Germany, the proportion of hyperfunctioning TNs is approximately 20% and increases in larger TNs to up to 27%. Due to the low risk of malignancy in hyperfunctioning TNs, no further procedures to rule out malignancy are necessary. The risk of malignancy of hypofunctioning TNs is significantly higher. Thus, a thyroid scintigraphy is a useful diagnostic tool in Germany.

Imaging of Prostate-Specific Membrane Antigen Expression in Metastatic Differentiated Thyroid Cancer Using 68Ga-HBED-CC-PSMA PET/CT.

PURPOSE: The prostate-specific membrane antigen (PSMA) was shown to be overexpressed on the neovasculature of several malignancies. Here, the role of Ga-HBED-CC-PSMA PET/CT for the detection of PSMA expression in patients with metastasized differentiated thyroid cancer (DTC) was evaluated. METHODS: Six patients with iodine-negative and F-FDG-positive metastasized DTC (mean TG, 1616 ng/mL) received 71-93 MBq of the Ga-labeled PSMA ligand and underwent PET/CT at 62 ± 7 minutes p.i.. Tumor accumulation capacity of the tracer and the detection rate of local recurrences and metastases were compared with F-FDG. Tracer uptake was quantified in terms of the SUVmax. RESULTS: In 5 of 6 patients, sites of putative metastatic disease could be identified using Ga-HBED-CC-PSMA PET/CT. All lesions detected with Ga-HBED-CC-PSMA PET/CT (n = 42) were confirmed by F-FDG PET/CT or conventional CT imaging. Using Ga-HBED-CC-PSMA PET/CT, all tumor lesions identified with F-FDG PET/CT imaging could be visualized in 3 of 5 patients. In 2 patients, only the most prominent lesions detected with F-FDG PET/CT imaging were visualized by Ga-HBED-CC-PSMA PET/CT. Ga-HBED-CC-PSMA uptake ranged from low in 1 patient (mean SUVmax 3.3) to intermediate (1 patient; mean SUVmax, 6.1) to intense (3 patients; mean SUVmax, 12.8, 16.2, and 18.3). The highest SUVmax values were observed for a bone lesion, reaching 39.7. CONCLUSIONS: These preliminary results indicate that Ga-HBED-CC-PSMA PET/CT might be suitable for staging of patients with metastasized DTC. Ga-HBED-CC-PSMA PET/CT could be useful for the identification of patients who might qualify for PSMA-targeted radionuclide therapy because of high PSMA uptake.

Value of 18 F-FDG PET/MRI for the outcome of CT-guided facet block therapy in cervical facet syndrome: initial results.

INTRODUCTION: The aim of this study was to evaluate the ability of 18 F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18 F-FDG PET/MRI) to detect PET-positive cervical facet arthropathy and identify patients who benefit from facet block therapy. METHODS: Ten patients with cervical facet syndrome (mean age: 65 ± 12 years) underwent 18 F-FDG PET/MRI of the neck. Focal 18 F-FDG uptake in PET-positive facet joints served as target for computed tomography (CT)-guided facet blocks. In PET-negative patients, the target joint for facet block therapy was selected by current clinical standards considering the level of maximum facet arthrosis and pain. Neck pain was measured on visual analogue scale (VAS) before and after therapy. Bone marrow signal intensity (SI) ratio on turbo inversion recovery magnitude (TIRM) images and maximum standard uptake values (SUVmax) was calculated for each facet joint. Pearson's correlation coefficient (r) was calculated between bone marrow SI ratios on TIRM and SUVmax. RESULTS: 18 F-FDG PET/MRI detected PET-positive facet arthropathy in six patients. Patients with PET-positive facet arthropathy had significantly less pain compared with the pretreatment pain 3 h (P = 0.002), 4 weeks (P = 0.002) and 3 months (P = 0.026) after facet block therapy. Pain did not change significantly in patients with PET-negative facet arthropathy. TIRM SI ratio was higher in PET-positive facet arthropathy than in PET-negative facet arthropathy (P < 0.001). Correlation was strong between bone marrow SI ratio on TIRM images and SUVmax (r = 0.7; P < 0.001). CONCLUSIONS: 18 F-FDG PET/MRI can detect PET-positive cervical facet arthropathy and help to identify patients benefitting from facet block therapy. Bone marrow TIRM SI ratio might be a surrogate for PET-positive facet arthropathy.

Distinguishing synchronous from metachronous manifestation of distant metastases: a prognostic feature in differentiated thyroid carcinoma.

AIM: Distant metastasis has a negative impact on survival in differentiated thyroid carcinoma (DTC). The timing of this manifestation, however, is of unknown prognostic relevance. The aim of this retrospective study was to investigate the potential significance of discriminating synchronous versus metachronous distant metastases (SDM vs. MDM) for the outcome of patients with DTC. METHODS: We retrospectively analyzed a consecutive cohort of n = 89 patients with distant metastases of DTC (43 with follicular, 46 with papillary DTC histology; mean age 52.6 ± 17.7 years) undergoing radioiodine treatment at our institution. All patients were treated with the same protocol consisting of ablative radioiodine therapy (RIT, 3.7 GBq) and one post-ablation treatment after 3 months (3.7-11.1 GBq). Further cycles of RIT were administered for recurrent, progressive or newly developed metastatic disease. We distinguished 2 types of distant metastases according to the time of manifestation: SDM (within ≤12 months after DTC diagnosis) and MDM (occurring >12 months after diagnosis). Tumor-related survival was analyzed using the Kaplan-Meier method. Uni- and multivariate analyses including the Cox proportional hazards model were performed with a significance level of p < 0.05. RESULTS: The mean follow-up period was 13.8 ± 1.2 years. SDM were present in 49 (55.1 %), MDM in 40 (44.9 %) patients. MDM were associated with shorter tumor-related survival (p = 0.002). 5-year and 10-year survival rates were 68.5 % and 34.8 % for MDM, and 84.3 % and 66.9 % for SDM, respectively. Within both age subgroups of <45 and ≥45 years, SDM were also linked with longer survival. No effect on tumor-related survival was found for the co-variables sex, lymph node metastases and histologic type. CONCLUSION: Distinguishing synchronous from metachronous manifestation of distant metastases may add an important prognostic feature to risk stratification in DTC, as proven metachronous appearance is associated with impaired survival.

High Level of Agreement Between Pretherapeutic 124I PET and Intratherapeutic 131I Imaging in Detecting Iodine-Positive Thyroid Cancer Metastases.

UNLABELLED: The aim of this retrospective study was to assess the level of agreement between PET and scintigraphy using diagnostic amounts of (124)I and therapeutic amounts of (131)I, respectively, in detecting iodine-positive metastases in patients with differentiated thyroid carcinoma. METHODS: The study included patients who underwent PET /: CT 24 and 120 h after administration of approximately 25 MBq of (124)I and subsequently underwent imaging 5-10 d after administration of 1-10 GBq of (131)I. For each patient, the intratherapeutic (131)I imaging comprised a whole-body scintigraphy scan and a SPECT/CT scan of the neck to distinguish between metastatic and thyroid remnant tissues. Iodine uptake was rated as a metastatic focus if located outside the thyroid bed. Lesion- and patient-based analyses were performed. RESULTS: The study included 137 patients with 227 metastases iodine-positive on both functional imaging modalities. In the lesion-based analysis, (124)I PET and (131)I imaging detected 98% (223/227) and 99% (225/227) of the iodine-positive metastases, respectively; the level of agreement between (124)I PET and (131)I imaging was 97% (221/227). Four metastases (3 lymph node and 1 bone) in 4 patients were (124)I-negative but (131)I-positive, and 2 lymph node metastases in 2 patients were (131)I-negative but (124)I-positive. In the patient-based analysis, 61 of the 137 patients presented with iodine-positive metastases. (124)I PET and (131)I imaging detected at least one iodine-positive metastasis in 97% (59/61) and 98% (60/61) of the patients, respectively. The level of agreement was 95% (58/61). Both imaging modalities concordantly identified 76 of 137 patients without pathologic iodine uptake. CONCLUSION: Because of the high level of agreement, pretherapeutic (124)I PET/CT is an adequate methodology in the detection of iodine-positive metastases and can be used as a reliable tool for staging of thyroid cancer patients and individualized treatment planning.

68Ga-DOTATOC PET/CT in Patients with Iodine- and 18F-FDG-Negative Differentiated Thyroid Carcinoma and Elevated Serum Thyroglobulin.

This study evaluated the impact of 68Ga-DOTATOC PET/CT in detecting recurrence or metastases in differentiated thyroid carcinoma (DTC) patients with elevated serum thyroglobulin and both negative radioiodine imaging and negative 18F-FDG PET/CT. METHODS: 68Ga-DOTATOC PET/CT (CT without contrast, low-dose) was performed on average 6 wk after negative 18F-FDG PET/CT (CT contrast-enhanced, full-dose) in 15 consecutive radioiodine-negative DTC patients with elevated and rising thyroglobulin. Visual assessment of 68Ga-DOTATOC PET/CT images used a 4-point scale for classification of lesions (0, no pathologic findings; 1, benign; 2, equivocal; 3, malignant). PET findings were correlated with the histologic subtype of tumor, levels of serum thyroglobulin, and morphologic findings on full-dose CT and neck ultrasound. Histology or clinical and imaging follow-up served as a reference standard. Analysis was performed on a patient and lesion basis. RESULTS: 68Ga-DOTATOC PET/CT was true-positive in 5 patients (10 tumor lesions) and was false-positive in 1 patient. The rate of positive 68Ga-DOTATOC PET/CT was significantly higher in poorly differentiated/oxyphilic carcinomas (4/4 patients) than in papillary (1/5) or follicular (0/6) tumors. Thyroglobulin levels tended to be higher in patients with tumor localization on 68Ga-DOTATOC PET/CT, but differences were not significant. In 2 of 5 patients with true-positive findings on 68Ga-DOTATOC PET/CT, CT alone but not ultrasound identified 2 of 10 tumor lesions, but in both patients 68Ga-DOTATOC-PET/CT revealed further tumor lesions not detected on CT alone. CONCLUSION: 68Ga-DOTATOC PET/CT should be considered in the case of negative 18F-FDG PET/CT in radioiodine-negative DTC patients with elevated and rising thyroglobulin. Imaging with 68Ga-DOTATOC appears promising especially in poorly differentiated and oxyphilic subtypes of DTC.

Prognostic impact of incomplete surgical clearance of radioiodine sensitive local lymph node metastases diagnosed by post-operative (124)I-NaI-PET/CT in patients with papillary thyroid cancer.

PURPOSE: Nodal involvement is an independent risk factor of recurrence in papillary thyroid cancer (PTC). Neither the international guidelines nor the recently introduced ongoing risk adaptation concept consider the extent of initial surgical clearance of radioiodine sensitive lymph node metastases in their stratification systems. We investigated the prognostic relevance of incomplete initial surgical clearance in patients with purely lymphogeneous metastatic PTC (pN1 M0) despite successful radioiodine therapy. Accurate assessment of pre-ablative nodal status was attempted using PET/CT studies with both (124)I-NaI and (18)F-FDG along with high-resolution cervical ultrasound. METHODS: Sixty-five patients with histologically diagnosed lymph node metastases (pN1 M0) were retrospectively analyzed. Patients with iodine-negative lymph node metastases diagnosed by (18)F-FDG PET/CT or distant metastases were excluded from the analysis. The association of disease recurrence with the pre-ablative nodal status, as well as other baseline characteristics, were examined applying nonparametric tests for independent samples and multiple regression analysis. Patients with persistent lymph node metastases in (124)I-NaI PET/CT were further divided according to the additional presence or absence of FDG-uptake in (18)F-FDG PET/CT. Survival analyses were performed using Kaplan-Meier curves and the Cox proportional hazards model for uni- and multivariate analyses to assess the influence of prognostic factors on progression free survival (PFS). RESULTS: Incomplete metastatic lymph node resection captured by (124)I-NaI PET/CT (n = 33) was an independent risk factor for recurrence (61 % vs 25 %, p = 0.006) and shorter PFS (46 months vs not reached, HR 4.0 [95 %-CI, 1.7-9.2], p = 0.001). Ultrasound could detect lymph node metastases only in 19/33 patients (58 %). Among patients with positive nodal status, FDG-avidity of metastatic iodine positive lymph nodes worsened the outcome (16 vs 69 months, p = 0.047). From all other investigated factors including age, N-stage (N1a vs N1b), and T-Stage (T4 vs T1-3), only large tumor size (pT4) had a significant impact on PFS (HR 2.9 [95 %-CI, 1.3-6.4], p = 0.007). CONCLUSIONS: Incomplete initial surgical clearance of lymph node metastases even after successful radioiodine therapy may increase the chances of recurrence and is an independent risk factor for impaired survival of patients with PTC. Pre-ablative (dual tracer PET/CT) imaging with (124)I-Na and (18)F provides a prognostic tool for these patients and may considerably complement the current risk stratification systems.

Initial [18F]FDG PET/CT in high-risk DTC patients. A three-year follow-up.

UNLABELLED: In a previous paper, we published the impact of initial [18F]FDG PET/CT (FDG-PET/CT) in high-risk patients with differentiated thyroid cancer (DTC) and described the changes in therapy management. The aim of the present study was to evaluate the prognostic impact of the initial FDG-PET/CT on a patient's follow-up over three years and the rate of complete remission. PATIENTS, METHODS: This study included 109 DTC patients who underwent radioiodine treatment (RIT), including post-therapeutic whole-body scintigraphy with FDG-PET/CT and a follow-up over three years. The follow-up included high-resolution sonography of the neck and determination of serum Tg as well as Tg antibodies every six months. The results of initial FDG-PET/CT and whole-body scintigraphy were compared with the status after three years of follow-up. RESULTS: 24/109 patients (22%) presented FDG-positive lesions, 22/109 patients (20%) only iodine-positive lesions, and 63/109 patients (58%) neither FDG-positive nor iodine-positive lesions. After three years, 83/109 patients (76%) revealed full remission, 15/109 patients (14%) tumour persistence and 11/109 patients (10%) a progressive disease. The negative predictive value (NPV) was calculated for patients without FDG-positive lesions (NPV 85%) and patients without any lesions (NPV 91%) regarding full remission in the follow-up. CONCLUSION: FDG-PET/CT has a high NPV (85% to 91%) in DTC patients regarding recurrence-free follow-up after three years. The change in patient management in patients with iodine-negative lesions can lead to a higher rate of full remissions in the follow-up after additional surgery. Therefore, FDG-PET/CT should be performed in all high-risk DTC patients in the context of the first RIT to improve patient management and risk stratification.

PSMA Ligands for Radionuclide Imaging and Therapy of Prostate Cancer: Clinical Status.

Prostate cancer (PCa) is the most common malignancy in men worldwide, leading to substantial morbidity and mortality. At present, imaging of PCa has become increasingly important for staging, restaging, and treatment selection. Until recently, choline-based positron emission tomography/computed tomography (PET/CT) represented the state-of-the-art radionuclide imaging technique for these purposes. However, its application is limited to patients with high PSA levels and Gleason scores. Prostate-specific membrane antigen (PSMA) is a promising new target for specific imaging of PCa, because it is upregulated in the majority of PCa. Moreover, PSMA can serve as a target for therapeutic applications. Currently, several small-molecule PSMA ligands with excellent in vivo tumor targeting characteristics are being investigated for their potential in theranostic applications in PCa. Here, a review of the recent developments in PSMA-based diagnostic imaging and therapy in patients with PCa with radiolabeled PSMA ligands is provided.

Does 18F-FDG PET/MRI reduce the number of indeterminate abdominal incidentalomas compared with 18F-FDG PET/CT?

OBJECTIVE: Incidental masses of abdominal organs are a relevant problem in radiological examinations. The aim of this study was to evaluate whether simultaneous (18)F-fluorodeoxyglucose ((18)F-FDG) PET/MRI, because of its higher soft-tissue contrast and the diversity of available pulse sequences, can reduce the number of indeterminate abdominal incidentalomas compared with (18)F-FDG PET/computed tomography (CT). MATERIALS AND METHODS: In this retrospective study, we enrolled 173 patients (91 women and 82 men, mean age 55.8±14.6 years) who underwent contrast-enhanced (18)F-FDG PET/CT on the same day for oncological indications. Data sets were examined in a random order by two readers noting incidentalomas and incidental tracer uptake of the liver, kidneys, spleen, pancreas, adrenal glands, and gallbladder. Findings were categorized into three categories: most likely malignant, indeterminate, and most likely benign. In addition, the most relevant MR sequence for the final decision was recorded for each incidentaloma. The numbers of benign, indeterminate, and malignant findings on (18)F-FDG PET/CT and (18)F-FDG PET/MRI were compared. A subgroup analysis was carried out to detect potential differences with respect to lesion location (organwise) and lesion consistency (solid vs. cystic). RESULTS: A total of 649 upper abdominal incidentalomas were found. (18)F-FDG PET/MRI detected more incidentalomas (n=635) than contrast-enhanced (18)F-FDG PET/CT (n=407, P<0.001). Using (18)F-FDG PET/MRI, significantly fewer incidentalomas were categorized as indeterminate compared with (18)F-FDG PET/CT (n=27 vs. 91, P<0.001). This was true for cystic (P<0.001) as well as solid masses (P<0.001). Seventy incidentalomas categorized as indeterminate on contrast-enhanced (18)F-FDG PET/CT could be clarified as most likely benign by (18)F-FDG PET/MRI, whereas only six lesions rated as benign by (18)F-FDG PET/CT were classified as indeterminate in (18)F-FDG PET/MRI. (18)F-FDG PET/MRI compared with contrast-enhanced (18)F-FDG PET/CT had significantly fewer indeterminate findings in the liver (P<0.001), kidneys (P=0.012), and adrenal glands (P=0.002); differences for the spleen (P=0.5) were not significant. CONCLUSION: (18)F-FDG PET/MRI identifies more incidentalomas than (18)F-FDG PET/CT, but significantly reduces the number of indeterminate incidental findings of abdominal organs.

Ethnicity, Clothing Style, and Body Mass Index are Significant Predictors of Vitamin D Insufficiency in Germany.

OBJECTIVE: To analyze risk factors for vitamin D insufficiency in Germany with respect to ethnicity, sex, and clothing style. METHODS: We analyzed the routine diagnostic work-ups of 1,231 adult (45.9 ± 17.9 years old) German (n = 1,034) and Turk residents (n = 197) referred with nonspecific symptoms to the Thyroid Centers at St. Elisabeth-Hospital in Dorsten, Germany and Bottrop, Germany to assess for metabolic diseases. All subjects underwent a routine examination that consisted of a questionnaire, lab tests for 25-hydroxyvitamin-D (25OHD), and thyroid profile. Turk females with traditional clothing (headscarf and covered legs and arms) were considered to wear "covered clothing." Logistic-regression was performed to identify factors that could predict vitamin D deficiency (<20 ng/mL) and insufficiency (20-30 ng/mL). RESULTS: Vitamin D insufficiency was seen in 33% of Germans and 74.1% of Turks, and vitamin D deficiency was present in 11.3% and 44.2% of Germans and Turks, respectively (P<.001). The mean 25OHD value in Turk females with covered clothes was lower than that in Turk females with conventional clothing (16.3 ± 12.3 vs. 27.2 ± 15.8, P<.001). Vitamin D insufficiency was present in 86.0% of Turk females with covered clothing versus 62.8% with conventional clothing (odds ratio [OR] = 3.6, P = .002). Ethnicity, body mass index (BMI), and clothing style were significant predictors of vitamin D deficiency and insufficiency by logistic regression (P<.001). CONCLUSIONS: (1) Vitamin D insufficiency among Turk residents in Germany is higher compared to Germans. The highest prevalence was present in Turk females with covered clothing. (2) Monitoring vitamin D in Turk residents in Germany is warranted. (3) Vitamin D supplements and access to facilities with sunlight exposure for females with covered clothing and all individuals with poor diets or limited access to sun exposure may prevent future health burden due to vitamin D insufficiency.

Assessment of lesion response in the initial radioiodine treatment of differentiated thyroid cancer using 124I PET imaging.

UNLABELLED: (124)I PET/CT images from differentiated thyroid cancer patients were retrospectively analyzed to assess the relationship between absorbed radiation dose (AD) to lesions and their response after radioiodine therapy. METHODS: Patients received serial (124)I PET/CT scans before and after their first radioiodine treatment. The pretherapy PET data were used to segment the lesion volumes and to predict the therapy-delivered ADs after administration of the therapeutic (131)I activity. The segmentation method's lower volume limit of determinability was a sphere of 0.80 mL, which classified the lesions into a known-volume group (>0.80 mL) or a small-volume group (≤0.80 mL) with their respective average and minimum ADs. The posttherapy PET data were used to assess the lesion-based therapy success. In the known-volume group, the response rate was calculated on the basis of lesions that received average ADs above the generally accepted threshold of 85 Gy for metastases and 300 Gy for thyroid remnants (TRs) and was expressed as the percentage of completely responding lesions. In the small-volume group, the metastasis and TR responses were evaluated for 3 minimum-AD groups: 5 to 10 Gy (TR, 5 to 30 Gy), >10 to 85 Gy (TR, >30 to 300 Gy), and >85 Gy (TR, >300 Gy). Their response rates were calculated in terms of the percentage of completely responding lesions in each minimum-AD group. RESULTS: In total, 59 lesions in 17 patients were amenable to reliable volume estimation. The response rates were 63%, 88%, and 90% for lymph node metastases (LMs), pulmonary metastases, and TRs, respectively. The response rates of 168 small lesions in 34 patients were more than 82% for LMs and more than 91% for TRs in each of the 3 minimum-AD groups; all small pulmonary metastases responded completely. CONCLUSION: In the known-volume group, the response rate for TRs matched well with historical data derived using (131)I scintigraphy imaging, whereas the response rate for LMs was not as high as expected, which may be explained by too short a follow-up time for a few LMs and a higher sensitivity of PET imaging. Small lesions were treated effectively, suggesting that they are considerably smaller than 0.80 mL.

Whole-body [¹8F]FDG PET/MRI vs. PET/CT in the assessment of bone lesions in oncological patients: initial results.

OBJECTIVES: To compare [(18)F]FDG PET/MRI with PET/CT for the assessment of bone lesions in oncologic patients. METHODS: This prospective study included 67 patients with solid tumours scheduled for PET/CT with [(18)F]FDG who also underwent a whole-body PET/MRI scan. The datasets (PET/CT, PET/MRI) were rated by two readers regarding lesion conspicuity (four-point scale) and diagnostic confidence (five-point scale). Median scores were compared using the Wilcoxon test. RESULTS: Bone metastases were present in ten patients (15%), and benign bone lesions in 15 patients (22%). Bone metastases were predominantly localized in the pelvis (18 lesions, 38%) and the spine (14 lesions, 29%). Benign bone lesions were exclusively osteosclerotic and smaller than the metastases (mean size 6 mm vs. 23 mm). While PET/CT allowed identification of 45 of 48 bone metastases (94%), PET/MRI allowed identification of all bone metastases (100%). Conspicuity of metastases was high for both modalities with significantly better results using PET/MRI (p < 0.05). Diagnostic confidence in lesion detection was high for both modalities without a significant difference. In benign lesions, conspicuity and diagnostic confidence were significantly higher with PET/CT (p < 0.05). CONCLUSIONS: [(18)F]FDG PET/MRI shows high potential for the assessment of bone metastases by offering superior lesion conspicuity when compared to PET/CT. In hypersclerotic, benign bone lesions PET/CT still sets the reference. KEY POINTS: • PET/MRI and PET/CT are of equal value for the identification of disease-positive patients • PET/MRI offers higher lesion conspicuity as well as diagnostic confidence • PET/MRI is an attractive new alternative for the assessment of bone metastases.

Pre-therapeutic blood dosimetry in patients with differentiated thyroid carcinoma using 124-iodine: predicted blood doses correlate with changes in blood cell counts after radioiodine therapy and depend on modes of TSH stimulation and number of preceding radioiodine therapies.

OBJECTIVE: Pre-therapeutic blood dosimetry prior to a high-dose radioiodine therapy (RAIT) is recommended and a blood dose of 2 Gy is considered to be safe. In this study, changes in the blood cell count after radioiodine therapy of high risk differentiated thyroid carcinoma (DTC) were analyzed and compared with the results of the pre-therapeutic blood dosimetry using 124I. Moreover, the influence of different modes of TSH stimulation and the number of preceding radioiodine therapies on the blood dose were assessed. METHODS: 198 patients with locally advanced or metastasized DTC received a pre-therapeutic blood dosimetry using 124I. To analyze the influence of the modes of TSH stimulation and the number of preceding RAITs on blood dose subgroups were built as follows: patients with endogenous TSH stimulation versus patients with exogenous TSH stimulation and patients with no preceding RAIT versus patients with at least one preceding RAIT. In 124/198 patients subsequent RAIT was performed. In 73/124 patients, hemograms were performed from day 2 to 12 month after RAIT. RESULTS: There was no high-grade bone marrow toxicity (i.e. ≥ grade 3) in patients receiving less than 2 Gy blood dose-independent of the therapeutic history. Within the first month after radioiodine therapy, there was an overall decrease in the white blood cell and platelet counts. The erythrocyte count was essentially stable. There was a correlation between cell count decrease and predicted blood doses (Spearman's correlation coefficient >-0.6 each) for the white cell line and the platelets. With regard to the subgroups, the blood dose per administered 131I activity (BDpA) was significantly higher in patients with endogenous TSH stimulation (median 0.08 Gy/GBq) than in patients with exogenous TSH stimulation (0.06 Gy/GBq) and in patients with no previous RAIT (0.08 Gy/GBq) compared to patients who had previously undergone at least one RAIT (0.07 Gy/GBq). CONCLUSIONS: The range of BDpA among DTC patients is rather wide. Our results suggest that lower blood doses can be expected when using exogenous TSH stimulation and blood doses are generally higher at first RAIT compared to subsequent RAITs. Thus, we advise to make blood dosimetry standard praxis prior to a high-activity RAIT.

¹8F-FDG PET/CT changes therapy management in high-risk DTC after first radioiodine therapy.

PURPOSE: Advanced tumour stage and initial metastases are associated with reduced general and tumour-free survival in patients with differentiated thyroid carcinoma. Optimal initial therapy is mandatory for a positive patient outcome, but can only be performed if all non-iodine-avid tumour lesions are known before planning treatment. We analysed the benefit of (18)F-FDG PET/CT at initial diagnosis in patients with high-risk differentiated thyroid carcinoma and determined whether the (18)F-FDG PET/CT results led to a deviation from the standard procedure, which consists of two consecutive radioiodine treatments with thyroid hormone suppression in between and no additional imaging, with individual patient management. METHODS: The study group comprised 90 consecutive patients with either extensive or metastasized high-risk differentiated thyroid carcinoma who received (18)F-FDG PET/CT after the first radioiodine treatment approximately 4 weeks after thyroidectomy under endogenous TSH stimulation. We carried out PET/CT imaging with low-dose CT without contrast medium, which we only used for attenuation correction of PET images. RESULTS: (18)F-FDG PET/CT was positive in 26 patients (29%) and negative in 64 patients (71%). Compared to the results of posttherapeutic (131)I whole-body scintigraphy, the same lesions were PET-positive in 7 of the 26 patients, different lesions were PET-positive in 15 patients, and some PET-positive lesions were the same and some were different in 4 patients. TNM staging was changed due to the PET results in 8 patients. Management was changed in 19 of the 90 patients (21%), including all patients with only FDG-positive lesions and all patients with both FDG-positive and iodine-positive lesions. Age was not a predictive factor for the presence of FDG-positive lesions. FDG-positive and iodine-positive lesions were associated with high serum thyroglobulin. However, at low serum thyroglobulin values, tumour lesions (iodine- and/or FDG-avid) were also diagnosed. Thus, the serum thyroglobulin value prior to the first radioiodine treatment cannot be used as a predictor of the presence of FDG-positive lesions. CONCLUSION: (18)F-FDG PET/CT resulted in a change of therapeutic procedure in 11 of 90 patients and in a change of patient management through additional diagnostic measures in 8 of 90 patients, and is consequently very helpful in initial staging. At our hospital, (18)F-FDG PET/CT in high-risk patients with differentiated thyroid carcinoma has been established as an initial staging modality.

Effects of rosiglitazone on radioiodine negative and progressive differentiated thyroid carcinoma as assessed by ¹²4I PET/CT imaging.

AIM: The aim of this study was to evaluate the redifferentiative and antiproliferative effects of rosiglitazone in patients with progressive differentiated thyroid cancer (DTC) without or with negligible overall radioiodine uptake. MATERIALS AND METHODS: A total of 9 patients with progressive DTC with either no or only negligible radioiodine accumulation were enrolled in this study. Oral rosiglitazone treatment was applied for 6 months (4 mg per day for 2 weeks followed by 8 mg per day). The compatibility of the medication was initially checked twice weekly and then weekly by laboratory tests and clinical evaluation of side effects. The assessments of alterations in the doses absorbed by the tumor and in lesion sizes over the course of rosiglitazone treatment were performed using serial ¹²4I positron emission tomography and computed tomography imaging. The assessment time points were before enrollment and 3 and 6 months posttreatment initiation. RESULTS: Lesion dosimetry indicated that 5 of 9 patients had an improved lesion absorbed dose per administered activity (LDpA), yielding in radioiodine therapy treatment in 4 patients. One third of the patients (3/9) were unchanged with regard to LDpA, and 1 of 9 had deteriorated LDpA. Volumetric analyses revealed that lesion sizes were regredient in 3 of 9 patients, stable in 4 of 9, and was progressive in 1 of 9. The medication was well-tolerated, and no patient developed clinically important toxicity associated with rosiglitazone treatment. In 2 of 9 of the patients, the medication was terminated after 3 months as a precaution due to progressive heart disease in one patient and bone fracture within a known osteolytic bone lesion in another patient. It is not clear that these complications were caused by rosiglitazone. CONCLUSION: Rosiglitazone appears to be suitable as off-label therapy in radioiodine-negative and progressive DTC that lacks therapy alternatives. In Europe, rosiglitazone was removed for label use because of reported side effects during diabetes treatment. Further investigations of other available glitazone compounds are necessary.

Diagnostic accuracy of virtual 18F-FDG PET/CT bronchoscopy for the detection of lymph node metastases in non-small cell lung cancer patients.

UNLABELLED: The aim of this study was to determine the diagnostic accuracy of (18)F-FDG PET/CT bronchoscopy for the detection of regional lymph node metastases in non-small cell lung cancer (NSCLC) patients; potential differences in the maximum standardized uptake value (SUVmax), mean SUV (SUVmean), short-axis diameter, and distance to the airways when comparing true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) lymph nodes; the smallest bronchus diameter accessible by virtual bronchoscopy; and the duration from the start of the virtual (18)F-FDG PET/CT bronchoscopy viewing tool until the images were displayed. METHODS: Sixty-one consecutive NSCLC patients (mean age ± SD, 58 ± 10 y) underwent whole-body (18)F-FDG PET/CT. From these data, virtual (18)F-FDG PET/CT bronchoscopies were reconstructed. The duration from the start of the tool until the display of virtual bronchoscopy images was determined. The diagnostic accuracy of (18)F-FDG PET/CT bronchoscopy for the detection of regional lymph node metastases was evaluated on a lesion basis. Axial (18)F-FDG PET/CT scans served as the standard of reference. The SUVmax, SUVmean, short-axis diameter, and distance to the airways of regional lymph nodes were measured. Lymph nodes were classified as TP, FP, TN, and FN. The smallest bronchus diameter accessible by (18)F-FDG PET/CT bronchoscopy was measured. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of virtual (18)F-FDG PET/CT bronchoscopy for the detection of lymph node metastases were 76%, 87%, 85%, 79%, and 81%, respectively. The differences between the SUVmax, SUVmean, short-axis diameter, and distance to the airways of TP and FP as well as TN and FN lymph nodes were statistically significant (P < 0.05). The mean smallest diameter of accessible bronchi by (18)F-FDG PET/CT bronchoscopy was 3 mm. The mean time duration from the start of the virtual (18)F-FDG PET/CT bronchoscopy tool until the display of the images was 22 ± 7 s. CONCLUSION: Virtual fly-through 3-dimensional (18)F-FDG PET/CT bronchoscopy yields a high diagnostic accuracy for the detection of regional lymph node metastases and has access to bronchi even in the periphery of the lung. High SUVmax, high SUVmean, large small-axis diameter, and short distance to the airways aid detection of lymph node metastases with (18)F-FDG PET/CT bronchoscopy.