FDG PET and FDG PET/CT in patients with gastrointestinal stromal tumours.

Gastrointestinal stromal tumours (GISTs) are fairly rare neoplasms, constituting less than 3 % of all gastrointestinal malignancies. The integration of molecularly targeted treatment regimes (i.e., tyrosine kinase inhibitors) in clinical oncology has revolutionized the management of patients with irresectable GISTs or metastatic disease. Malignant GISTs usually display increased glucose metabolism and therefore (18)F-fluorodeoxyglucose (FDG) uptake within the scope of positron emission tomography (PET) scans. Nowadays, dual-modality FDG PET/CT (computed tomography) imaging is of considerable value in diagnostic work-up of patients with GISTs acquiring functional and anatomic information simultaneously. The following article sheds light on the impact of FDG PET and combined FDG PET/CT imaging in initial disease evaluation, detection of tumour recurrence and the early assessment of treatment response to molecularly targeted agents such as imatinib mesylate or sunitinib maleate.

Nuclear medicine in NET.

Neuroendocrine tumors (NET) are, despite increasing incidence, still rare, usually slow growing neoplasms with resemblance to nerve cells and the endocrine capability of hormone production. In contrast to commonly used conventional imaging procedures, nuclear imaging is feasible to visualize the presence of molecular biomarkers, particularly the overexpression of somatostatin receptors (sstr) with high diagnostic accuracy which has led to the establishment of somatostatin receptor scintigraphy (SRS) as essential component and gold standard of functional imaging in the workup of NET. Another major feature is the selection of patients with inoperable or metastasized tumors showing sufficient uptake for peptide receptor radionuclide therapy (PRRT). While somatostatin receptor PET and PET/CT using Ga-68-labeled SSR analogs represents the consistent further development of SRS, FDG-PET can only be used in tumors with high proliferative activity but not on a routine basis for imaging of neuroendocrine tumors. (18)F-DOPA represents an alternative PET tracer worth mentioning currently under assessment for NET imaging.

Assessment of Treatment Response to Lenvatinib in Thyroid Cancer Monitored by F-18 FDG PET/CT Using PERCIST 1.0, Modified PERCIST and EORTC Criteria-Which One Is Most Suitable?

Background: We aimed to compare the established metabolic response criteria PERCIST and EORTC for their applicability and predictive value in terms of clinical response assessment early after the initiation of lenvatinib therapy in patients with metastatic radioiodine-refractory (RAI) thyroid cancer (TC). Methods: In 25 patients treated with lenvatinib, baseline and 4-month follow-up F-18 FDG PET/CT images were analyzed using PERCIST 1.0, modified PERCIST (using SUVpeak or SUVmax) and EORTC criteria. Two groups were defined: disease control (DC) and progressive disease (PD), which were correlated with PFS and OS. Results: PERCIST, mPERCIST, PERCISTmax and EORTC could be applied in 80%, 80%, 88% and 100% of the patients based on the requirements of lesion assessment criteria, respectively. With PERCIST, mPERCIST, PERCISTmax and EORTC, the patients classified as DC and PD ranged from 65 to 68% and from 32 to 35%, respectively. Patients with DC exhibited a longer median PFS than patients with PD for EORTC (p < 0.014) and for PERCIST and mPERCIST (p = 0.037), respectively. Conclusion: EORTC and the different PERCIST criteria performed equally regarding the identification of patients with PD requiring treatment changes. However, the applicability of PERCIST 1.0 using SULpeak seems restricted due to the significant proportion of small tumor lesions.

Diagnostic Reference Levels for nuclear medicine imaging in Austria: A nationwide survey of used dose levels for adult patients.

PURPOSE: To assess dose levels in routine nuclear medicine (NUC) procedures in Austria as a prior to a legislative update of the National Diagnostic Reference Levels (NDRL). METHOD: As part of a nationwide survey of common NUC-examinations between June 2019 and November 2019, data sets were collected from 33 Austrian hospitals with NUC equipment. All hospitals were asked to report the NUC imaging devices in use (model, type, year of manufacture, detector material, collimators), the standard protocol parameters for selected examinations (standard activity, collimator, average acquisition time, reconstruction type, use of time-of-flight) and to report data from 10 representative examinations (e.g. injected activity, weight), incl. the most common NUC-examinations for planar imaging/SPECT and PET. Median/mean values for injected activity were calculated and compared to current Austrian and international NDRL. A Pearson correlation coefficient was computed comparing different variables. RESULTS: In total, all 33 hospitals (100% response rate) reported data for this study for 60 SPECT devices, 21 PET/CT devices and 23 scintigraphy devices. Fixed activity values for scintigraphy/SPECT and PET were employed by about 90% and 56% of the hospitals, respectively. The most widely performed examinations for scintigraphy/SPECT are bone imaging, thyroid imaging, renal imaging (with MAG3/EC) and lung perfusion imaging (in 88% of the hospitals) and F-18 FDG-PET studies for oncology indications (in 100% of the hospitals). Significant correlations were found for patient weight and injected activity (scintigraphy/SPECT), use of iterative reconstruction and injected activity (PET) as well as size of field-of-view and injected activity (PET). CONCLUSIONS: The reported injected activity levels were comparable to those in other countries. However, for procedures for which NDRL exist, deviations in injected activities of >20% compared to the NDRL were found. These deviations are assumed to result mainly from advances in technology but also from deviations between NDRL and prescribed activities as given in the information leaflets of the radiopharmaceuticals.

[Thyroid and pregnancy]. / Schilddrüse und Schwangerschaft.

Screening for thyroid dysfunction is recommended among certain groups of women, who plan a pregnancy, for example women with history of hyperthyroid or hypothyroid disease, with type 1 diabetes or other autoimmune disorders or women with previous therapeutic head or neck irradiation, in the case of infertility. Management of thyroid disease during pregnancy requires special consideration because pregnancy induces major changes in thyroid function, and maternal thyroid disease can have adverse affects on the pregnancy and the foetus. Under ideal conditions there is a cooperation among several healthcare professionals, such as endocrinologists, nuclear medicine physicians, gynaecologists, neonatologists and if necessary surgeons. This article surveys the physiological and pathological changes of thyroid, their diagnosis and therapy in the case of women in childbearing age, women with unfulfilled desire to have children, pregnant women, as well as women after delivery.

High cathepsin K levels in men with differentiated thyroid cancer on suppressive L-thyroxine therapy.

BACKGROUND: Thyroid hormone administration is associated with low bone density in some studies. The aim of the present study was to evaluate the influence L-thyroxine, in doses used to treat patients with a history of thyroid carcinoma, on serum cathepsin K and other markers of bone metabolism. Cathepsin K is thought to have a role in osteoclast mediated bone resorption. METHODS: A group of male patients with differentiated thyroid cancer (DTC) on suppressive L-thyroxine therapy (DTC-group; n = 51; mean age 57 years; TSH < 0.1 mU/L) was selected as a model for hyperthyroidism. The results were compared to a group of healthy euthyroid men (control-group; n = 50; mean age 58 years; TSH 1.5 +/- 0.9 mU/L). RESULTS: In the DTC-group the median value of cathepsin K was 6.9 pmol/L, in the control group 4.8 pmol/L (p = 0.0052; highly significant [h.s.]). There was a significant negative correlation of cathepsin K with age (r = -0.279, p = 0.028). The analysis of various bone associated parameters revealed an increase of serum crosslaps in the DTC-group versus euthyroid controls (p = 0.03). A significant correlation could be found for cathepsin K and osteoprotegerin (p = 0.002). CONCLUSION: Cathepsin K is increased by a suppressive L-thyroxine therapy and decreases with increasing age. The increased cathepsin K levels seen in DTC-patients on suppressive L-thyroxine therapy are likely to contribute to accelerated bone degradation in these patients.

Is there a role for sandostatin treatment in patients with progressive thyroid cancer and iodine-negative but somatostatin-receptor-positive metastases?

INTRODUCTION: The aim of our study was to determine whether treatment with a long-acting somatostatin-receptor analogue is effective in patients with (131)I-negative but somatostatin-receptor-positive metastases from dedifferentiated and anaplastic thyroid cancer. MATERIALS AND METHODS: Twelve patients were screened for the study. All of them showed progressive disease confirmed by radiologic evaluation, increasing serum thyroglobulin (Tg), and negative diagnostic or posttherapeutic (131)I whole-body scans (WBS). Eight of 12 patients (4 males and 4 females; age range, 57-89 years; 1 papillary thyroid cancer; 4 poorly differentiated follicular thyroid cancer; 1 follicular and anaplastic thyroid cancer; 2 anaplastic thyroid cancer) showed positive somatosatin-receptor expression in Tc-99m depreotide WBS/SPECT (Tc-99m Dep.WBS). Initially, in all patients fluorine-18 2-fluoro-2- D-glucose-positron emission tomography-computed tomography ((18)F-FDG-PET-CT), Tc-99m Dep.WBS, and Tg measurements were performed. In the case of positive receptor scintigraphy, patients were treated with 20mg Sandostatin LAR (Novartis Pharmaceuticals, Basel, Switzerland) once per month intramuscularly over a period of 6 months followed by repeated (18)F-FDG-PET-CT, Tc-99m Dep.WBS, and Tg measurement to determine metabolic activity and tumor size. In case of tumor progression, the dose was increased to 30mg of Sandostatin LAR once per month. RESULTS: Only 3 patients were able to undergo long-term treatment. Two patients were treated with octreotide long-acting release (LAR) for 1 year and 1 patient for 1(1/2) years. All patients showed progressive disease during the treatment: an increase of serum Tg on one hand and an increase in the number of lesions and extent in tumor size visible on FDG-PET-CT and Tc-99m Dep.WBS on the other. During the treatment there was no change in receptor expression, nevertheless, clear tumor progression under therapy with a somatostatin analogue was visible in FDG-PET-CT and in Tc-99m Dep.WBS. CONCLUSION: Our data demonstrate that all of our patients treated with a somatostatin analogue showed clinical progression and that our attempt to achieve a stabilization of the disease failed.

Fine-Needle Aspiration with Immunohistochemistry Using a Modified Scrape Cell Block Technique for the Diagnosis of Thyroid and Parathyroid Nodules.

OBJECTIVE: To evaluate the diagnostic accuracy of a modified scrape cell block (SCB) technique in a large series of patients. The technique was especially developed and tested for fine-needle aspiration of thyroid and parathyroid nodules. STUDY DESIGN: Eighty-two ultrasound-guided fine-needle aspiration specimens with the sonographic aspect of a thyroid (n = 33) or a possible parathyroid nodule (n = 49) were studied. Immunohistochemistry (IHC) was used on cell blocks containing plasma, thromboplastin, and selected 3-dimensional cell aggregates scraped off Papanicolaou-stained smears. Antibodies for chromogranin A, thyroglobulin, parathyroid hormone, calcitonin, and carcinoembryonic antibody (CEA) were used. In cases of reduced immunosensitivity or suspected metastases or rare primary tumors, additional IHC markers were employed. RESULTS: Chromogranin A was expressed in all 28 parathyroid adenomas (PA), in 7 of 8 hyperplastic parathyroid glands, and in 13 of 14 medullary thyroid carcinomas (MTC). When combining positivity for chromogranin A and calcitonin/CEA, the specificity for the detection of MTC was 100%. Parathyroid hormone was expressed in 26 of 36 parathyroid nodules (72.2%). When combining follicular microarchitecture and expression of chromogranin A, the specificity for the detection of parathyroid tissue was 97%. CONCLUSION: With the modified SCB technique, accurate cytological diagnoses were obtained in 97.6% of 82 patients.

Performance evaluation of the Biograph mCT Flow PET/CT system according to the NEMA NU2-2012 standard.

BACKGROUND: The purpose of the study is to evaluate the physical performance of a Biograph mCT Flow 64-4R PET/CT system (Siemens Healthcare, Germany) and to compare clinical image quality in step-and-shoot (SS) and continuous table motion (CTM) acquisitions. METHODS: The spatial resolution, sensitivity, count rate curves, and Image Quality (IQ) parameters following the National Electrical Manufactures Association (NEMA) NU2-2012 standard were evaluated. For resolution measurements, an (18)F point source inside a glass capillary tube was used. Sensitivity measurements were based on a 70-cm-long polyethylene tube, filled with 4.5 MBq of FDG. Scatter fraction and count rates were measured using a 70-cm-long polyethylene cylinder with a diameter of 20 cm and a line source (1.04 GBq of FDG) inserted axially into the cylinder 4.5 cm off-centered. A NEMA IQ phantom containing six spheres (10- to 37-mm diameter) was used for the evaluation of the image quality. First, a single-bed scan was acquired (NEMA standard), followed by a two-bed scan (4 min each) of the IQ phantom with the image plane containing the spheres centered in the overlap region of the two bed positions. In addition, a scan of the same region in CTM mode was performed with a table speed of 0.6 mm/s. Furthermore, two patient scans were performed in CTM and SS mode. Image contrasts and patient images were compared between SS and CTM acquisitions. RESULTS: Full Width Half Maximum (FWHM) of the spatial resolution ranged from 4.3 to 7.8 mm (radial distance 1 to 20 cm). The measured sensitivity was 9.6 kcps/MBq, both at the center of the FOV and 10 cm off-center. The measured noise equivalent count rate (NECR) peak was 185 kcps at 29.0 kBq/ml. The scatter fraction was 33.5 %. Image contrast recovery values (sphere-to-background of 8:1) were between 42 % (10-mm sphere) to 79 % (37-mm sphere). The background variability was between 2.1 and 5.3 % (SS) and between 2.4 and 6.9 % (CTM). No significant difference in image quality was observed between SS and CTM mode. CONCLUSIONS: The spatial resolution, sensitivity, scatter fraction, and count rates were in concordance with the published values for the predecessor system, the Biograph mCT. Contrast recovery values as well as image quality obtained in SS and CTM acquisition modes were similar.

F-18 fluorodeoxyglucose positron-emission tomography in the diagnosis of tumor recurrence and metastases in the follow-up of patients with breast carcinoma: a comparison to conventional imaging.

AIM: To evaluate the role of F-18-fluorodeoxyglucose positron-emission tomography (F-18 FDG PET) in the follow-up of breast carcinoma in case of clinical suspicion of local recurrence or distant metastases and/or tumor marker increase in correlation to conventional imaging. MATERIAL AND METHODS: Retrospective analysis of the results of F-18 FDG PET (ECAT ART(R), Siemens CTI MS) of 62 patients (age 58.5 +/- 12.8) with surgically resected breast carcinoma (time interval after surgery, 86 +/- 82 months, mean follow-up 24 +/- 12.6 months). Patient- and lesion-based comparison with conventional imaging (CI) including mammography (MG), ultrasonography (US), computerized tomography (CT), magnetic resonance imaging (MRI), radiography (XR) and bone scintigraphy (BS). Furthermore, we evaluated the influence on tumor stage and therapeutic strategy. A visual qualitative evaluation of lesions was performed. RESULTS: On a patient base, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for detecting local recurrence or distant metastases were calculated to be 97%, 82%, 87%, 96% and 90% compared with 84%, 60%, 73%, 75% and 74% with CI. On a lesion base, significantly more lymph node (84 vs. 23, P < 0.05) and fewer bone metastases (61 vs. 97, P < 0.05) could be detected by using F-18 FDG PET compared with CI. Sclerotic bone lesions were predominantly detected by BS. On the other hand, there were several patients with more FDG positive bone lesions and also mixed FDG positive/Tc-99m methylenediphosphonate (MDP) negative and FDG negative/Tc-99m MDP positive metastases. In case of normal tumor markers, sensitivity, specificity, PPV, NPV and accuracy for detecting local recurrence or distant metastases were calculated to be 100%, 85.0%, 78.6%, 100% and 90.3% for FDG PET and 80%, 50%, 50%, 80% and 61.5% for CI. An upstaging could be observed in 9.7% (6/62) and downstaging in 12.9% (8/62), leading to a change in therapeutic regimen in 13 patients (21%). CONCLUSIONS: F-18 FDG PET demonstrates apparent advantages in the diagnosis of metastases in patients with breast carcinoma, compared with conventional imaging on a patient base. On a lesion base, significantly more lymph node and less bone metastases can be detected by using F-18 FDG PET compared with conventional imaging, including bone scintigraphy. In patients with clinical suspicion but negative tumor marker profile, too, F-18 FDG PET seems to be a reliable imaging tool for detection of tumor recurrence or metastases. Considering the high predictive value of F-18 FDG PET, tumor stage and therapeutic strategy will be reconsidered in several patients.

Fluorine-18-fluorodeoxyglucose positron emission tomography in the preoperative assessment of thyroid nodules in an endemic goiter area.

BACKGROUND: The aim of this study was to evaluate the usefulness of fluorine-18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in the preoperative assessment of suspicious thyroid nodules. METHODS: A total of 43 patients were examined before surgical resection. In all patients, imaging was obtained at 70 minutes after the intravenous administration of 180 MBq (18)F-FDG. Standard uptake values (SUVs) were calculated. RESULTS: A total of 16 patients with thyroid carcinomas (11 papillary, 3 follicular, 2 anaplastic), 23 thyroid adenomas (11 microfollicular, 10 Hurthle cell, 2 macrofollicular), and 4 patients with degenerative goiter were found. (18)F-FDG uptake in Hurthle cell adenoma, thyroid cancer, microfollicular adenoma, degenerative goiter, and macrofollicular adenoma was 4.4 +/- 2.2, 3.7 +/- 1.9, 1.6 +/- 0.3, 1.2 +/- 0.2, and 0.9 +/- 0.1, respectively. Significant differences were observed between thyroid carcinomas and both microfollicular adenomas and degenerative goiters (P < 0.05), and between Hurthle cell adenomas and both microfollicular adenomas as well as degenerative goiter (P < 0.05). For diagnosis of thyroid carcinoma, 100% sensitivity, 63% specificity, and 100% negative predictive value was found when a cutoff value for SUV of 2 was used. CONCLUSIONS: Our results indicate that thyroid carcinomas, in contrast to most benign thyroid nodules, demonstrate significantly increased glucose metabolism. (18)F-FDG PET is unlikely to differentiate successfully all benign tumors from malignant tumors, but it can help select patients who need surgery, especially if cytology is inconclusive or malignancy cannot be excluded.

Goiter prevalence and urinary iodide excretion in a formerly iodine-deficient region after introduction of statutory lodization of common salt.

The objective of this epidemiologic study was to determine the volume of the thyroid gland as well as urinary iodine excretion in dependence on age and gender in a population from an area of low natural iodine supply now receiving iodine prophylaxis. In 430 persons from three communities in the province of Carinthia, Austria, we determined thyroid volume via sonography as well as urinary iodide excretion. As in numerous other European countries, natural iodine supply is insufficient in Austria. Therefore, to reduce goiter incidence, iodization of common salt with 10 mg potassium iodide (KI) per kilogram of NaCl was made mandatory in Austria in 1963 by federal law. In 1990, the amount of iodine addition was increased to 20 mg KI per kilogram of NaCl. Our results show that mean urinary iodide excretion in the persons investigated was altogether satisfactory (males: 163.7 microg of iodine per gram of creatinine; females: 183.3 microg of iodine per gram of creatinine). Goiter prevalence was 34.3% in women and 21.3% in men. An increase in goiter occurrence with age was noted in both genders. The increase in goiter prevalence was particularly obvious in the age group older than 40, i.e., among those participants who had spent at least a certain span of their lives in an area of iodine deficiency. Thus, the most likely reason for the persistently high goiter prevalence is not current iodine deficit but rather the high number of goiters that had developed previously at the time of iodine deficiency and were unable to undergo regression in spite of today's comparatively good iodine supply situation.

Combined PET/CT in the follow-up of differentiated thyroid carcinoma: what is the impact of each modality?

PURPOSE: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a well-established method in the follow-up of patients with differentiated thyroid carcinoma (DTC), elevated thyroglobulin (Tg) and negative 131I scans. This retrospective clinical study was designed to evaluate the impact of computed tomography (CT) and that of FDG-PET in combined FDG-PET/CT examinations on the restaging of DTC patients. METHODS: Forty-seven FDG-PET/CT scans of 33 patients with a history of DTC, elevated Tg levels and negative 131I uptake or additionally suspected 131I-negative lesions were studied. PET and CT images were analysed independently by an experienced nuclear medicine specialist and a radiologist. Afterwards a final consensus interpretation, the gold standard in our department, was provided for the fused PET/CT images and, if available, for supplementary investigations. RESULTS: Thirty-five investigations (74%) revealed pathological FDG-PET/CT findings. In summary, 25 local recurrences, 62 lymph node metastases and 122 organ metastases (41 lung, 60 bone, 21 other organs) were diagnosed. In 36 out of 47 examinations (77%), the original PET diagnoses were modified in the final consensus interpretation owing to the CT assessments. In 8 of the 35 pathological FDG-PET/CT examinations (23%), the final consensus interpretation of the PET/CT images led to an alteration in the treatment plan. CONCLUSION: PET/CT is a powerful fusion of two pre-existing imaging modalities, which not only improves the diagnostic value in restaging DTC patients with elevated Tg and negative 131I scan, but also provides accurate information regarding subsequent treatment options and may lead to a change in treatment management.

Role of Fluorodeoxyglucose PET in Inflammatory Bowel Disease: A Review.

Inflammatory bowel disease (IBD) requires a complex diagnostic workup. In contrast to endoscopy and cross-sectional imaging methods, scintigraphy enables a complete survey of the whole small and large bowel intestinal tract with a single noninvasive examination. For detection of IBD, 80% to 90% sensitivity and 92% to 100% specificity can be found for conventional scintigraphy. A new imaging method like fluorine-18 (F-18) fluorodeoxyglucose PET has been shown to be useful in tumor diagnostics. A major problem in PET is the limited anatomic information and nonspecific tracer uptake within the colon, however, which may lead to false-positive results. New imaging methods like combined PET/CT can help to solve the problem, because physiologic tracer uptake can be easily distinguished from pathologic lesions as a result of the anatomic detail provided by CT.

[Thyroid and cardiovascular system]. / Schilddrüse und Herzkreislaufsystem.

The cardiocirculatory changes in hyperthyroidism seem to be an accommodation to the increased metabolic demands and lead to an increased perfusion of the peripheral tissues. Due to the influence of elevated thyroid hormone levels, contractility, stroke volume, resting heart rate, and contraction and relaxation velocity of the left ventricle increase. Caused by direct effect on the smooth vascular muscle, systemic vascular resistance is decreased with the consequence of a diminished afterload and an increased cardiac efficiency. The activation of the renin-angiotensin-aldosteron system and the increased production of erythropoietin additionally lead to an increased blood volume, which increases cardiac preload together with the increased venous backflow. Manifest hypothyroidism is characterized by bradycardia and diastolic dysfunction in rest and systolic dysfunction at stress. Despite a slight increase of diastolic blood pressure due to an increased systemic vascular resistance, blood pressure remains nearly stable because of diminished cardiac output. Hypercholesterinaemia and diastolic hypertension in hypothyroid patients can lead to the development of arteriosclerosis and coronary heart disease (CHD). Also subclinical hypothyroidism is associated with a significantly higher risk for arteriosclerosis and CHD, whereas subclinical hyperthyroidism seems to be associated with an increased mortality for all reasons, especially for cardiovascular diseases.

[Scintigraphic findings in a patient with sickle-cell thalassemia and recurrent pain attacks]. / Szintigraphische Befunde bei einem Patienten mit Sichelzell-Thalassämie und rezidivierenden Schmerzattacken.

The case of an eight years old African boy who suffers from sickle cell-thalassemia is presented. In the course of the disease frequent pain attacks occurred within the abdomen and extremities, recently also within the trunk. Local pain, at some occasions in combination with local swelling and always positive laboratory parameters for inflammation, hindered a solely clinical differentiation between bone infarcts and osteomyelitis. Bone scintigraphy, eventually in combination with bone marrow scintigraphy, can assist the clinician in the differentiation of aseptic bone infarcts versus secondary osteomyelitis. Based on the presented case scintigraphic results for bone infarcts, osteomyelitis and special scintigraphic pattern seen in sickle cell disease are presented. Furthermore, problems regarding the interpretation of the scintigraphies in relation to the delayed time after the beginning of pain attacks are discussed.