[Therapy concepts for thyroid carcinoma]. / Therapiekonzepte beim Schilddrüsenkarzinom.

Theranostics via the sodium iodide symporter (NIS) offer a unique option in differentiated thyroid carcinoma. The diagnostic and therapeutic nuclides have similar uptake and kinetics, making the NIS the most important theranostic target in this disease. Radioiodine refractory thyroid carcinomas (RRTC) are characterised by reduced/absent NIS expression, thus eliminating this structure as a theranostic target. Also due to limited therapeutic options, there are approaches to generate new theranostic targets in RRTC, via the expression of somatostatin receptors (SSTR) or the prostate-specific membrane antigen (PSMA), but the current evidence does not yet allow a final evaluation of the prospects of success.

Clinical Presentation, Treatment, and Outcome of Parathyroid Carcinoma: Results of the NEKAR Retrospective International Multicenter Study.

OBJECTIVE: In this retrospective cohort study, we describe the clinical presentation and workup of parathyroid carcinoma (PC) and determine its clinical prognostic parameters. Primary outcome was recurrence free survival. SUMMARY BACKGROUND DATA: PC is an orphan malignancy for which diagnostic workup and treatment is not established. METHODS: Eighty-three patients were diagnosed with PC between 1986 and 2018. Disease-specific and recurrence-free survivals were estimated with the Kaplan-Meier method. Risk factors for recurrence were identified by binary logistic regression with adjustment for age and sex. Thirty-nine tumors underwent central histopathological review. RESULTS: Renal (39.8%), gastrointestinal (24.1%), bone (22.9%), and psychiatric (19.3%) symptoms were the most common symptoms. Surgical treatment was heterogeneous [parathyroidectomy [PTx)] alone: 22.9%; PTx and hemithyroidectomy: 24.1%; en bloc resection 15.7%; others 37.3%] and complications of surgery were frequent (recurrent laryngeal nerve palsy 25.3%; hypoparathyroidism 6%). Recurrence of PC was observed in 32 of 83 cases. In univariate analysis, rate of recurrence was reduced when extended initial surgery had been performed (P = 0.04). In multivariate analysis low T status [odds ratio (OR) = 2.65, 95% confidence interval (CI) 1.02-6.88, P = 0.045], N0 stage at initial diagnosis (OR = 6.32, 95% CI 1.33-30.01, P = 0.02), Ki-67 <10% (OR = 14.07, 95% CI 2.09-94.9, P = 0.007), and postoperative biochemical remission (OR = 0.023, 95% CI 0.001-0.52, P = 0.018) were beneficial prognostic parameters for recurrence-free survival. CONCLUSION: Despite a favorable overall prognosis, PC shows high rates of recurrence leading to repeated surgery and postoperative recurrent laryngeal nerve palsy and hypoparathyroidism. In view of the reduced recurrence rate in cases of extended surgery, ipsilateral completion surgery may be considered when PC is confirmed.

Rhombencephalitis associated with isolated Zic4-antibodies in Paraneoplastic cerebellar degeneration: a case report.

BACKGROUND: Cerebellar degeneration as a consequence of a malignancy is a rare condition most commonly related to the presence of anti-Yo, anti-Hu, and anti-Tr/DNER antibodies. In recent years, several reports have indicated Zinc-finger protein 4 (Zic4) antibodies being associated with paraneoplastic cerebellar degeneration (PCD) in patients with small cell lung carcinoma. However, the prevalence and the significance of Zic4-antibodies may be underestimated due to their co-occurrence with more frequent antibodies such as anti-Hu. A literature review of isolated Zic4 mediated paraneoplastic syndromes yielded 14 cases reporting mainly benign clinical courses when treated early. CASE PRESENTATION: We present the case of a 67-year-old woman with progressive Zic4 antibody mediated PCD and rhombencephalitis. Immunomodulatory treatment, including intravenous methylprednisolone, plasmaphereses, and intravenous immunoglobulin (IVIG) was administered. Small cell lung cancer (SCLC) was detected, lobectomy performed and cyclophosphamide started. Despite this considerable therapeutic effort, rhombencephalitis led to defiant dysautonomia. CONCLUSION: Paraneoplastic syndromes related to isolated Zic4 antibodies are rare and typically show a benign clinical course. Here, we present the first case of a rapidly progressive isolated Zic4 associated PCD and rhombencephalitis. Despite considerable therapeutic efforts, the patient passed away on autonomic dysfunction, highlighting the significance of Zic4 associated disease.

Recent advances in nuclear medicine in endocrine oncology.

PURPOSE OF REVIEW: The purpose is to review recent advances concerning the role of nuclear medicine in endocrine oncology. RECENT FINDINGS: For I therapy of thyroid cancer a thyrotropin (TSH) more than 30 mU/l has for many years been deemed a condition sine qua non. However, new data show that patients with lower TSH levels at the time of ablation have the same rate of successful ablation as those with TSH more than 30 mU/l.I-124 combined integrated positron emission tomography and computed X-ray tomography was shown to be highly accurate in predicting findings on posttherapy radioiodine scanning and was shown to have a high prognostic power.In neuroendocrine tumors, long-term complication rates of peptide receptor radionuclide therapy were reported. Furthermore first preclinical and clinical results of peptide receptor radionuclide therapy with somatostatin receptor antagonists were published.In nuclear medicine, prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and therapy is of interest. PSMA was shown to also be expressed in neoplasms of the thyroid, the adrenal glands and neuroendocrine tumors. SUMMARY: Further individualization of thyroid cancer patient care by means of I-124-positron emission tomography and computed X-ray tomography-based selection of the therapeutic strategy is possible. I therapy might not require as intensive TSH stimulation as thought previously. For endocrine-related malignancies PSMA targeting deserves further investigation.

Management of a metastasized high grade insulinoma (G3) with refractory hypoglycemia: case report and review of the literature.

Insulinomas represent the most common functional neuroendocrine tumor of the pancreas. They are usually solitary, benign, well differentiated (G1/G2) and curable by surgery. We describe the case of a 45 year old male Caucasian with a unique malignant, metastasized pancreatic insulinoma (Ki 67 of 70%, G3). To control excessive insulin production emanating in refractory hypoglycemia and growth of the highly proliferating tumor a multimodal therapeutic approach including the consecutive use of tumor debulking surgery, chemotherapy, TACE, SIRT, PRRT as well as a drug therapy with diazoxide, somatostatin analogs and everolimus was employed. Chemotherapy with carboplatin/etoposide plus everolimus provided the longest normoglycemic period. After progress chemotherapy with dacarbazine had the most positive effect, while debulking approaches such as surgery and liver directed therapies, as well as PRRT were less efficient with only transient success.

Imaging of firefly luciferase activity under antiangiogenic therapy in a heat shock protein 70-transfected melanoma tumor model.

We investigated the effect of targeted gene therapy on heat shock protein 70 (Hsp70) expression in a melanoma tumor model (M21). M21 cells transfected with a plasmid containing the firefly luciferase reporter gene (ffluc), whose expression is driven by the hsp70 (hspa1b) or the cytomegalovirus (CMV) promoter, were grown to a size of 600 mm3. Five animals in each group were intravenously treated with an Arg-Gly-Asp peptide-nanoparticle/Raf-1 kinase inhibitor protein [RGD-NP/RAF(-)] complex. Bioluminescence imaging (BLI) (IVIS, Xenogen, Alameda, CA) was performed at set time intervals. Western blot analysis of the HSP70 protein was simultaneously performed. The size of the treated M21 tumors was nearly constant (637.8 ± 33.4 mm3 vs 674.8 ± 34.4 mm3). BLI showed that if transcription was controlled by the CMV promoter, firefly luciferase activity decreased to 51.1% ± 8.3%. When transcription was controlled by the hsp70 promoter, the highest firefly luciferase activity (4.4 ± 0.3-fold) was observed after 24 hours. In accordance with BLI, Western blot analysis showed an increase in the level of HSP70, with the maximum detection 24 hours after the injection of the RGD-NP/RAF(-) complex. Targeted antiangiogenic therapy can induce luciferase activity where transcription is controlled by an hsp70 promoter and HSP70 protein in melanoma tumors.

Application of the American Thyroid Association Risk Assessment in Patients with Differentiated Thyroid Carcinoma in a German Population.

BACKGROUND: The American Thyroid Association (ATA) uses criteria to assess the risk for persistent disease in differentiated thyroid carcinoma (DTC) after radioiodine therapy (RAI). There are no data available showing that this classification can be adopted unadjusted by Germany. AIM: The aim of our study is to investigate whether the ATA classification can be applied to a German population for short-term prognosis. Furthermore, we investigated the influence of an age cutoff value. METHODS: We retrospectively analyzed 121 patients who were referred to our tertiary referral center. Patients were classified into risk categories, and the therapy response was determined according to ATA. RESULTS: A total of 73/83 (88%) ATA low-risk patients and 12/19 (63%) intermediate-risk patients showed an excellent response; 2/19 (11%) high-risk patients had a biochemical, and 6 (31%) had a structural incomplete response. Of all 39 patients ≥55 years, 84% had an excellent response. Using a cut off of 50 years, 50/62 (81%) of the older patients showed an excellent response. CONCLUSION: The ATA risk classification is able to estimate the response to RAI therapy in a German population. A shift from 55 to 50 years as an age cutoff value does not result in any relevant change in the treatment response.

[Therapy concepts for thyroid carcinoma]. / Therapiekonzepte beim Schilddrüsenkarzinom.

Theranostics via the sodium iodide symporter (NIS) offer a unique option in differentiated thyroid carcinoma. The diagnostic and therapeutic nuclides have similar uptake and kinetics, making the NIS the most important theranostic target in this disease. Radioiodine refractory thyroid carcinomas (RRTC) are characterised by reduced/absent NIS expression, thus eliminating this structure as a theranostic target. Also due to limited therapeutic options, there are approaches to generate new theranostic targets in RRTC, via the expression of somatostatin receptors (SSTR) or the prostate-specific membrane antigen (PSMA), but the current evidence does not yet allow a final evaluation of the prospects of success.

[High clinical value of bone scintigraphy as a staging method for breast cancer]. / Hohe klinische Wertigkeit der Skelettszintigrafie beim Staging des Mammakarzinoms.

BACKGROUND: Bone scintigraphy is a sensitive method for imaging bone metastases in patients with breast cancer. Despite its firm establishment in clinical routine, there are hardly any reliable data from larger homogeneous collectives on the value of bone scintigraphy in the context of staging of first diagnosed breast cancer patients. AIM: The aim of our work was to evaluate the real-life performance of bone scintigraphy as a staging examination in female patients with the initial diagnosis of breast cancer. PATIENTS AND METHODS: We retrospectively evaluated the data of the patients examined in the year 2015 with the first diagnosis of breast cancer at the University Hospital Marburg by bone scintigraphy. In addition a follow-up over a period of 30 months after the first bone scintigraphy was performed. For this purpose we evaluated whether the results of this initial diagnostic could be confirmed in following diagnostic. RESULTS: 207/258 patients showed no suspicious findings in the initial bone scintigraphy, 48 had an unclear finding, which is why 42 patients received further diagnostics. In follow-up, new bone metastases were found in 4 patients, all of these had scintigraphic findings in the primary diagnosis, which were considered "unclear". Depending on the evaluation of the event (suspicious for metastasis/suspicious for metastasis and unclear), the sensitivity was 37.5%/100%, the specificity 100%/80%, the positive predictive value 100%/15.7% and the negative predictive value 98%/100%. CONCLUSION: By using bone scintigraphy and, if necessary, subsequent further imaging or histological clarification, a clinically significant diagnosis was obtained in 99,2% of the examined patients and confirmed in the follow-up. This result shows the good real-life performance of bone scintigraphy as a staging examination in patients with first diagnosed breast carcinomas.

Real-Life Performance of F-18-FDG PET/CT in Patients with Cervical Lymph Node Metastasis of Unknown Primary Tumor.

BACKGROUND: Neoplasms in the head and neck region possess higher glycolytic activity than normal tissue, showing increased glucose metabolism. F-18-Flourodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) can identify an unknown primary tumor (CUP). AIM: The aim of this study was to assess the real-life performance of F-18-FDG-PET/CT in detecting primary sites in patients with cervical lymph node metastasis of CUP. METHODS: A retrospective data analysis of 31 patients who received FDG-PET/CT between June 2009 and March 2015 in a CUP context with histologically confirmed cervical lymph node metastasis was included. RESULTS: In 48% of the patients (15/31), PET/CT showed suspicious tracer accumulation. In 52% of the patients (16/31), there was no suspicious radiotracer uptake, which was confirmed by the lack of identification of any primary tumor in 10 cases until the end of follow-up. FDG-PET/CT had a sensitivity of 67%, specificity of 91%, PPV of 92%, and NPV of 63% in detecting the primary tumor. Additionally, PET/CT showed suspicious tracer accumulation according to further metastasis in 32% of the patients (10/31). CONCLUSION: FDG-PET/CT imaging is a useful technique for primary tumor detection in patients in a cervical CUP context. Furthermore, it provides information on the ulterior metastasis of the disease.

Theranostics in Thyroid Cancer.

The main targeting structure for theranostics in thyroid cancer is the sodium-iodine symporter (NIS), which has been used in clinical routine for the diagnosis and treatment of thyroid diseases for more than 70 years. Because the different iodine (I) nuclides (123I, 124I, 131I) have the same kinetics, uniquely congruent theranostics are possible in differentiated thyroid cancer. Besides the NIS, there are further possibilities by using expression of somatostatin receptors or the expression of the prostate-specific membrane antigen, for example, in radioiodine-refractory differentiated thyroid cancer, medullary thyroid cancer, or anaplastic thyroid cancer.

Perioperative diagnostics of patients referred for radioiodine therapy of differentiated thyroid carcinoma: referral center experience in an iodine-insufficient country.

PURPOSE: The interdisciplinary "Martinique-Principles" of four international professional societies concerned with the patient management of differentiated thyroid cancer (DTC) patients were agreed upon. Differences in perioperative diagnostics can lead to differences in clinical decision founding regarding the treatment of thyroid carcinoma. Our aim was to analyze the perioperative diagnostics of patients referred for postoperative I-131 therapy of DTC. METHODS: We retrospectively examined the data of 142 patients who were referred to our center for the first course of postsurgical I-131 therapy. We extracted data on perioperative diagnostics. RESULTS: Fine-needle biopsy (FNB) was performed in 27/142 patients. In 17 patients, FNB yielded findings suspicious of malignancy, in 3 patients a follicular lesion was reported. An intraoperative frozen section analysis was performed in 79/142 patients. 5/63 patients showed already a cytologically proven malignancy. In 10/79 patients, the frozen section had a nonmalignant result, although DTC was found on final assessment. In 2/79 patients, frozen section analysis was indecisive, although the final report confirmed DTC. In the remaining 67 patients, frozen section yielded DTC. CONCLUSIONS: There is room for improvement in perioperative diagnostics surrounding thyroid surgery, currently many procedures are performed without adequate information on potential presence of thyroid cancer. More frequent use of FNB might be able to decrease the number of unnecessary thyroid surgeries, increased use of frozen section might decrease the number of second operations and might contribute to less discordance between experts in the field of DTC treatment.

Effect of Kinase Inhibitors on the Technetium-99m Uptake into Thyroid Carcinoma Cells In Vitro.

BACKGROUND/AIM: We evaluated the potential of the kinase inhibitors sorafenib, lenvatinib and selumetinib on increasing the uptake of technetium-99m into thyroid cancer cells. MATERIALS AND METHODS: Four established cell lines and three patient's cell cultures were treated with 0.1, 1 and 5 µM of sorafenib, lenvatinib and selumetinib for 72 hours. After incubation with 1 MBq of technetium-99m, the radioactivity uptake was measured. RESULTS: The experiments showed heterogeneous results. Maximum technetium-99m uptake increases of 312% (sorafenib), 326% (lenvatinib) and 759% (selumetinib) were obtained using the highest applied concentrations. In some tests, an uptake reduction or no effect was observed. CONCLUSION: Kinase inhibitors have a positive effect on technetium-99m uptake. Due to study limitations, a redifferentiating effect of the drugs could not be definitely proven. Unspecific cytotoxicity might have a confounding effect.

Prostate-Specific Membrane Antigen in Anaplastic and Poorly Differentiated Thyroid Cancer-A New Diagnostic and Therapeutic Target?

Several studies have demonstrated an expression of the prostate-specific membrane antigen (PSMA) in the cancer-related neovasculature of thyroid malignancies. Due to the poor prognosis and limited therapeutic options for patients with anaplastic (ATC) and poorly differentiated (PDTC) thyroid carcinoma, the aim of our study was to investigate the theranostic approach of PSMA expression in these patients. The PSMA uptake on Gallium-68 (68Ga)-PSMA-positron emission tomography/computed tomography (PET/CT) and glucose uptake on F-18-Fluordeoxyglucose (18F-FDG)-PET/CTs were analysed in two ATC and six PDTC patients. The PSMA expression in corresponding patients' tissue samples was detected by immunohistochemistry. In addition, various tissue sections from 22 ATC and six PDTC patients were examined concerning PSMA expression. 68Ga-PSMA-PET/CT showed heterogeneous PSMA expression among patients and lesions. Six of the eight analyzed patients (two ATC, four PDTC) showed increased glucose metabolism without increased PSMA uptake after PET/CT. In one patient (PDTC), 18F-FDG-PET/CT tracer uptake was positive and 68Ga-PSMA-PET/CT showed heterogeneous results. Another patient (PDTC) evidenced only PSMA-positive lesions and received two cycles of Lutetium-177 (177Lu)-PSMA therapy, which kept his disease stable for seven months. There was a correlation between immunohistochemical PSMA expression and uptake on 68Ga-PMSA-PET/CT in three of the examined patients. Twenty-seven of the analyzed 39 ATC and 13 of the analyzed 22 PDTC tissue sections showed a strong PSMA expression. Considering the rarity of PDTC and ATC, which is the reason for the small patient population we studied, the findings of this study confirm the high diagnostic sensitivity and superiority of 18F-FDG-PET/CT in comparison to 68Ga-PSMA-PET/CT in the diagnosis of ATC and PDTC. However, it can be suggested that 68Ga-PMSA-PET/CT can be considered as a beneficial adjunct to the well-established 18F-FDG-PET/CT for a few individual selected patients with ATC and PDTC to detect lesions not discovered by 18F-FDG-PET/CT and to determine patients' eligibility for a radioligand therapy. Radiolabelled PSMA-ligands may, in the future, represent a theranostic approach with only minor side effects for a few individual selected patients with ATC and PDTC who need alternative treatment options in case of progression when established therapies are no longer effective. However, due to the small sample size of our collective, larger studies are needed to allow for a final evaluation on the significance of PSMA-targeted diagnostic and therapy for ATC and PDTC.

Real-World Efficacy and Safety of Multi-Tyrosine Kinase Inhibitors in Radioiodine Refractory Thyroid Cancer.

Background: The management of patients with locally advanced or metastatic differentiated thyroid cancer (DTC) that is refractory to radioiodine (RAI) remains a therapeutic challenge. The multi-tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib have been approved based on phase 3 clinical trials. Patients and Methods: We aimed at describing the efficacy and safety of TKI treatment of RAI-refractory DTC in a real-world setting at six German referral centers. One hundred and one patients with locally advanced or metastatic RAI-refractory DTC treated with sorafenib, lenvatinib, and/or pazopanib were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated by using the Kaplan-Meier method. Results: Ninety-seven of 101 patients had progressive disease before TKI initiation. The median PFS for first-line treatment with sorafenib (n = 33), lenvatinib (n = 53), and pazopanib (n = 15) was 9 (95% confidence interval 5.2-12.8), 12 (4.4-19.6), and 12 months (4.4-19.6), respectively. The median OS for first-line treatment was 37 (10-64) for sorafenib, 47 (15.5-78.5) for lenvatinib, and 34 months (20.2-47.8) for pazopanib. Serious complications (e.g., hemorrhage, acute coronary syndrome, and thrombosis/venous thromboembolism) occurred in 16 out of 75 (21%) patients taking lenvatinib, in 3 out of 42 (7%) patients taking sorafenib, and in 3 out of 24 (13%) patients taking pazopanib. Conclusions: Sorafenib, lenvatinib, and pazopanib are effective treatment options in the majority of patients with RAI-refractory DTC. The PFS and six-month survival rate in patients treated with lenvatinib und pazopanib appear to compare favorably with sorafenib in the first-line treatment setting. However, a more advanced disease stage at treatment initiation in sorafenib- and pazopanib-treated patients in the era before TKI-approval and the retrospective nature of this study precludes a direct comparison of TKIs.

[Follow-up of differentiated thyroid cancer]. / Nachsorge beim differenzierten Schilddrüsenkarzinom.

The management of differentiated thyroid carcinoma has shown considerable changes in recent years, moving away from a fixed therapy regimen towards individual treatment strategies. The aim of our work (literature research) is to present current developments in the follow-up of differentiated thyroid cancer.For the management of individual follow-up, an initial evaluation and, at later time points, the re-evaluation of the risk of recurrence is crucial. The performance of I-131-diagnostics after radioiodine therapy can provide essential information and can be seen as a survey of a new baseline situation, in order to be able to draw a comparison in case of a rising Thyreoglobulin (Tg).The measurement of Tg with a highly sensitive assays shows a high negative predictive value. Negative Tg measurements with these assays seem to indicate complete remission even with Tg antibodies being present. An increasing Tg value in follow-up implies further diagnostic work-up, primarily neck ultrasonography. Sonographically suspicious findings should be subjected to fine needle biopsy, whereby in addition to cytological processing, determination of Tg from the sample can be recommended. If the suspicious lesion cannot be displayed sonographically and Tg values keep rising, computed tomography (CT) and magnetic resonance imaging (MRI) of the neck region can provide further information. FDG-PET/CT has also shown an excellent performance in this setting.The previously fixed therapy regimen has been realigned towards an individual treatment management. Current studies and guidelines lead to a repetitive recurrence risk evaluation and the adjustment of the aftercare planning to the individual risks with appropriately selected examination methods and personalized intervals of assessment.

Reference values for quantitative parameters in renal scintigraphy with Tc-99m-MAG3.

BACKGROUND: Reference values are the basis for an increase of standardisation and examiner independence, and thus an improvement in the inter-institutional comparability. However for renal Mercaptoacetyltriglycin (MAG3)-scintigraphy the establishment of such values however did not find its way into clinical routine despite the convincing advantages. AIM: The aim was to establish reference values for the decisive quantitative parameters of MAG3 renal scintigraphy. The reference values should help to significantly improve and facilitate the interpretation of the examination results in everyday clinical practice. METHODS: We retrospectively evaluated all MAG3 renal scintigraphies performed in the Department of Nuclear Medicine, University Hospital Marburg between 01/2014 and 08/2017. The total sample of non-pathological renal scintigrafies included 247 patients aged between 25 days and 88 years. All investigtions were performed according to the present guidelines of the German Association for Nuclear Medicine. We analysed the ratio from pulse count rate after 20 minutes/Time (T) max and the Tmax separately. RESULTS: Reference values for the Tmax and 20 min/T(max) count ratio of the MAG3 renal scintigraphy were defined for all adults over 18 years and divided by age catogories. For children aged 0-0.5 years and 0.5-2 years reference values for Tmax were defined. CONCLUSION: The results show a high degree of consistency with the reference values screened out in previous studies. This underlines the reliability of the reference values as a diagnostic tool in clinical application. The defined values are clinically feasible and promise a simplified and improved interpretation of the MAG3 renal scintigraphy.

Score-based improvement of the indication for surgical treatment of thyroid lesions.

BACKGROUND: The prevalence of focal lesions in the thyroid is high in Germany. In 2018 about 70 000 thyroid surgeries were performed, although the malignancy rate of such findings is low. For this reason it is important to conduct an adequate selection of patients for whom surgery is indicated. AIM: The aim of our work was to validate the preoperative indication for surgery of thyroid lesions based on an independent, self-developed clinical score. PATIENTS AND METHODS: The patient data were evaluated retrospectively over the period 2013 to 2014. A prerequisite for inclusion was that the patients had carried out their complete treatment in domo. The multiparametic score was determined retrospectively and ranges from 3 to 15. The subjective improvement of symptoms (self-disclosure > 6 months postoperatively) and the presence of malignant histology were evaluated as positive outcome parameters. RESULTS: From a collective of 180 patients, 36 patients could be included, in whom all score-relevant parameters had been surveyed. The score distribution was 10 % score 3, 12.5 % score 4, 25 % score 5, 25 % score 6, 12.5 % score 7, 7.5 % score 8, 5 % score 9 and 2.5 % score 10. Using ROC analysis shows an AUC of 0.903, which is a very good differentiation. With a CUT-off score of 7 or higher, 86 % of patients have benefited from surgery. CONCLUSION: Our score with the parameters clinical complaints, sonographically defined size of the thyroid and the cytological result of a fine needle biopsy can lead to an improvement of the indication for surgical treatment of thyroid nodules.

In vivo SPECT and real-time gamma camera imaging of biodistribution and pharmacokinetics of siRNA delivery using an optimized radiolabeling and purification procedure.

Single photon emission computed tomography (SPECT) imaging provides a three-dimensional method for exactly locating gamma emitters in a noninvasive procedure under in vivo conditions. For characterization of siRNA delivery systems, molecular imaging techniques are extremely helpful to follow biodistribution under in experimental animal studies. Quantification of biodistribution of siRNA and nonviral delivery systems using this technique requires efficient methods to stably label siRNA with a gamma emitter (e.g., 111In or 99mTc) and to purify labeled material from excesses of radiolabel or linkers. In the following study, we have optimized labeling and purification of siRNA, which was then applied as free siRNA or after complexation with polyethylenimine (PEI) 25 kDa for in vivo real-time gamma camera and SPECT imaging. Quantification of scintillation counts in regions of interest(ROIs) was compared to conventional scintillation counting of dissected organs, and the data acquired by imaging was shown to corroborate that of scintillation counting. This optimization and proof of principle study demonstrates that biodistribution and pharmacokinetics of siRNA and the corresponding polyplexes can be determined using SPECT, leading to comparable results as conventional methodology.

Unexpected 99mTc-tetrofosmin findings during myocardial perfusion scintigraphy: intraindividual comparison with PET/computed tomography.

OBJECTIVE: 99mTc-tetrofosmin single photon emission computed tomography (SPECT) is routinely used in the evaluation of coronary artery disease. A variety of different tumors, however, also demonstrate 99mTc-tetrofosmin uptake. We report six patients found with unexpected mediastinal and thoracic tumor uptake during Tc-tetrofosmin myocardial perfusion scintigraphy (MPS). MATERIALS AND METHODS: We investigated 2,155 patients with Tc-tetrofosmin MPS during 2006-2007. One thousand four hundred and eighty-six of these patients had no coronary history and were sent to our department due to newly developed thoracic complaint such as chest pain, dyspnea and others. Six hundred and sixty-nine patients had coronary history. All patients underwent 99mTc-tetrofosmin exercise study. Patients with unexpected extracardiac Tc-tetrofosmin findings during MPS were referred to PET/CT for further diagnostic investigation. Region of interest (ROI; 99mTc-tetrofosmin) and SUVmax (2-[F]fluoro-2-deoxy-D-glucose, F-FDG) were estimated and the results were compared with histological findings. RESULTS: Abnormal mediastinal and/or thoracic activities were visualized in six of the 2,155 patients with 99mTc-tetrofosmin images. Subsequently, the patients underwent resection of a thymoma (n=2), nonsmall cell lung cancer (n=1) and breast cancer (n=3). In the patients with breast cancer one was a male patient with ductal, invasive breast cancer. Benign thymomas showed high 99mTc-tetrofosmin ROI >4.0 and low F-FDG SUVmax <2.0, whereas low 99mTc-tetrofosmin ROI <2.0 were found in nonsmall cell lung cancer and breast cancer and high F-FDG SUVmax >2.5 in these malignant tumors. CONCLUSION: During Tc-tetrofosmin SPECT exercise stress tests performed in patients with suspected coronary artery disease, much more attention must be given to unexpected extracardiac uptakes. With 99mTc-tetrofosmin a large variety of different unknown tumors can be detected during MPS.