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European journal of nuclear medicine and molecular imaging (2022). doi:10.1007/s00259-022-06066-3, Published by Springer-Verl., Heidelberg [u.a.]

European journal of nuclear medicine and molecular imaging 48(5), 1371-1389 (2021). doi:10.1007/s00259-020-05094-1, Published by Springer-Verl., Heidelberg [u.a.]

Neuroendocrine tumours (NETs) arise from secondary epithelial cell lines in the gastrointestinal or respiratory system organs. The rate of development of these tumours varies from an indolent to an aggressive course, typically being initially asymptomatic. The identification of these tumours is difficult, particularly because the primary tumour is often small and undetectable by conventional anatomical imaging. Consequently, diagnosis of NETs is complicated and has been a significant challenge until recently. In the last 30 years, the advent of novel nuclear medicine diagnostic procedures has led to a substantial increase in NET detection. Great varieties of exclusive single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals for detecting NETs are being applied successfully in clinical settings, including [

BACKGROUND: Sore throat is a common reason for consultation of primary care physicians, pediatricians, and ENT specialists. The updated German clinical practice guideline on sore throat provides evidence-based recommendations for treatment in the framework of the German healthcare system. METHODS: Guideline revision by means of a systematic search of the literature for international guidelines and systematic reviews. All recommendations were developed by an interdisciplinary guideline committee and agreed by formal consensus. The updated guideline applies to patients aged 3 years and over. RESULTS: In the absence of red flags such as immunosuppression, severe comorbidity, or severe systemic infection, acute sore throat is predominantly self-limiting. The mean duration is 7 days. Chronic sore throat usually has noninfectious causes. Laboratory tests are not routinely necessary. Apart from non-pharmacological self-management, ibuprofen and naproxen are recommended for symptomatic treatment. Scores can be used to assess the risk of bacterial pharyngitis: one point each is assigned for purulent or inflamed tonsils, palpable cervical lymph nodes, patient age, disease course, and elevated temperature. If the risk is low (3 points), antibiotics can be taken immediately. Penicillin remains the first choice, with clarithromycin as an alternative for those who do not tolerate penicillin. The antibiotic should be taken for 5–7 days. CONCLUSION: After the exclusion of red flags, antibiotic treatment is unnecessary in many cases of acute sore throat. If administration of antibiotics is still considered in spite of patient education on the usual course of tonsillopharyngitis and the low risk of complications, a risk-adapted approach using clinical scores is recommended.

Breast cancer is the most frequent invasive malignancy and the second major cause of cancer death in female subjects mostly due to the considerable diagnostic delay and failure of therapeutic strategies. Thus, early diagnosis and possibility to monitor response to the treatment are of utmost importance. Identification of valid biomarkers, in particular new molecular therapeutic targets, that would allow screening, early patient identification, prediction of disease aggressiveness, and monitoring response to the therapeutic regimen has been in the focus of breast cancer research during recent decades. One of the intensively developing fields is nuclear medicine combining molecular diagnostic imaging and subsequent (radio)therapy in the light of theranostics. This review aimed to survey the current status of preclinical and clinical research using theranostic approach in breast cancer patients with potential to translate into conventional treatment strategies alone or in combination with other common treatments, especially in aggressive and resistant types of breast cancer. In addition, we present 5 patients with breast cancer who were refractory or relapsed after conventional therapy while presumably responded to the molecular radiotherapy with 177Lu-trastuzumab (Herceptin), 177Lu-DOTATATE, and 177Lu-FAPI-46.

Studies in nuclear medicine have shed light on molecular imaging and therapeutic approaches for oncological and nononcological conditions. Using the same radiopharmaceuticals for diagnosis and therapeutics of malignancies, the theranostics approach, has improved clinical management of patients. Theranostic approaches for nononcological conditions are recognized as emerging topics of research. This review focuses on preclinical and clinical studies of nononcological disorders that include theranostic strategies. Theranostic approaches are demonstrated as possible in the clinical management of infections and inflammations. There is an emerging need for randomized trials to specify the factors affecting validity and efficacy of theranostic approaches in nononcological diseases.

Neuroendocrine neoplasms make up a heterogeneous group of tumors with inter-patient and intra-patient variabilities. Molecular imaging can help to identify and characterize neuroendocrine tumors (NETs). Furthermore, imaging and treatment with novel theranostics agents offers a new, tailored approach to managing NETs. Recent advances in the management of NETs aim to enhance the effectiveness of targeted treatment with either modifications of known substances or the development of new substances with better targeting features. There have been several attempts to increase the detectability of NET lesions via positron emission tomography (PET) imaging and improvements in pretreatment planning using dosimetry. Especially notable is PET imaging with the radionuclide Copper-64. Increasing interest is also being paid to theranostics of grade 3 and purely differentiated NETs, for example, via targeting of the C-X-C motif chemokine receptor 4 (CXCR4). The aim of this review is to summarize the most relevant recent studies, which present promising new agents in molecular imaging and therapy for NETs, novel combination therapies and new applications of existing molecular imaging modalities in nuclear medicine.

// Anna Yordanova 1, * , Soha Mahjoob 1, * , Philipp Lingohr 2 , Jorg Kalff 2 , Andreas Turler 3 , Holger Palmedo 4 , Hans-Jurgen Biersack 1 , Glen Kristiansen 5 , Jamshid Farahati 6 , Markus Essler 1 and Hojjat Ahmadzadehfar 1 1 Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany 2 Department of Surgery, University Hospital Bonn, Bonn, Germany 3 Department of General and Visceral Surgery, Johanniter-Krankenhaus Bonn, Bonn, Germany 4 Institute of Radiology and Nuclear Medicine, PET-CT Center, Bonn, Germany 5 Institute of Pathology, University Hospital Bonn, Bonn, Germany 6 Department of Nuclear Medicine, Bethesda Hospital, Duisburg, Germany * These authors have contributed equally to this work Correspondence to: Hojjat Ahmadzadehfar, email: hojjat.ahmadzadehfar@ukbonn.de Keywords: sestamibi, MIBI, thyroid nodules, thyroid cancer, cold nodule Received: June 20, 2017 Accepted: September 16, 2017 Published: October 17, 2017 ABSTRACT [ 99m Tc]Tc-Sestamibi (MIBI) is an increasingly used tool for evaluation of thyroid nodules. However, there is a lack of evidence about the accuracy of this method in the European population. The aim of this study was to assess the utility of MIBI for the differentiation of thyroid nodules in a large cohort. 161 patients underwent MIBI, followed by a thyroidectomy. We used a dual phase MIBI protocol. Interpretation of the images included a scoring system from 0 (absent) to 3 (increased); this was to provide a scale for the uptake of the thyroid nodule in comparison to the paranodular tissue. Additionally, we evaluated the tracer uptake trend in late images compared to early images. We used the final histopathology as the reference standard. Scores 0-1 in early images, scores 0-2 in late images, and an absence of increasing uptake in the thyroid nodule in late images, showed the best predictive values to exclude malignancy, respectively (negative predictive value (NPV) 89%). Highest sensitivity (91%) for malignant nodules was evident in early images with a score 1-3. Highest specificity (91%) was obtained when the negative was defined as an absence of uptake-increase, in the late images. This study confirms that the most valuable feature of MIBI is the high NPV. Thus, with the appropriate interpretation method, high sensitivity and specificity, and moderate PPV can be obtained.

To date, several papers have been published about prostate-specific membrane antigen (PSMA)-based radioligand diagnostic and therapeutic approaches. This paper mainly provides information for nuclear medicine physicians that are clinically engaged in the diagnosis and treatment of prostate cancer patients. It aims to present the utility of PSMA imaging and therapy in a step-by-step practical approach; thus, it does not discuss radiochemistry and the molecular basics of PSMA.

Background Monocentric and retrospective studies indicate effectiveness of peptide receptor radionuclide therapy targeting somatostatin receptors of neuroendocrine neoplasms. We assessed overall and progression-free survival and adverse events of peptide receptor radionuclide therapy by a multi-institutional, board certified registry with prospective follow-up in five centres in Germany. Methods A total of 450 patients were included and followed for a mean of 24.4 months. Most patients had progressive low- or intermediate grade neuroendocrine neoplasms and 73% were pretreated with at least one therapy. Primary neuroendocrine neoplasms were mainly derived of pancreas (38%), small bowel (30%), unknown primary (19%) or bronchial system (4%). Patients were treated with Lutetium-177 in 54%, with Yttrium-90 in 17% and with both radionuclides in 29%. Overall and progression-free survival was determined with Kaplan–Meier curves and uni-variate log rank test Cox models. Findings Median overall survival of all patients was 59 (95% confidence interval [CI] 49–68.9) months. Overall survival was significantly inferior in the patients treated with Yttrium-90 solely (hazard ratio, 3.22; 95% CI, 1.83–5.64) compared to any peptide receptor radionuclide therapy with Lutetium-177. Grade II (hazard ratio, 2.06; 95% CI, 0.79–5.32) and grade III (hazard ratio, 4.22; 95% CI, 1.41–12.06) neuroendocrine neoplasms had significantly worse overall survival than grade I neuroendocrine neoplasms. Patients with small neuroendocrine neoplasms of small bowel had significantly increased survival (hazard ratio, 0.39; 95% CI, 0.18–0.87) compared to neuroendocrine neoplasms of other locations. Median progression-free survival was 41 (35.9–46.1) months and significantly inferior in patients treated with Yttrium solely (hazard ratio, 2.7; 95% CI, 1.71–4.55). Complete remission was observed in 5.6% of patients, 22.4% had a partial remission, 47.3% were stable and 4% were progressive as best response. Adverse events of bone marrow and kidney function higher than grade III occurred in 0.2–1.5% of patients. Interpretation These results indicate that peptide receptor radionuclide therapy is a highly effective therapy for patients with low to intermediate grade neuroendocrine neoplasms with minor adverse events.

Fur Patienten mit Lungenkarzinom ist ein prazises Staging von Lymphknoten- und Fernmetastasen die entscheidende Grundlage fur die Therapieplanung und insbesondere fur die Wahl des Operationsverfahrens. Die FDG-PET / CT stellt im Rahmen des diagnostischen Lungenkrebs-Algorithmus beim potentiell kurativem Therapieansatz das zentrale bildgebende Verfahren dar. Bei Patienten mit histologisch gesichertem Lungenkarzinom kann die FDG-PET / CT gegenuber der alleinigen CT die Genauigkeit des Lymphknoten- und Fernmetastasenstagings signifikant erhohen und als Ganzkorperuntersuchung zudem oft weitere Untersuchungen ersetzen. Prospektive Studien zeigen auch, dass durch den Einsatz der FDG-PET in der praoperativen Abklarung bei Patienten mit Lungenkarzinom die Anzahl unnotiger Thorakotomien und Mediastinoskopien signifikant reduziert werden kann.

Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with 177Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1–2 stage IV treated with 177Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial 99mTc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2 %). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1 %), minor response in 19 (31.1 %), stable disease in 29 (47.5 %) and progressive disease in 5 (8.2 %) patients. The disease control rate was 91.8 %. Median progression-free survival (PFS) and overall survival (OS) was 33 [95 % confidence interval (CI) 25–41] and 61 months (95 % CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were functionality [hazard ratio (HR) 2.1, 95 % CI 1.0–4.5, p = 0.05] and high plasma chromogranin A (CgA) levels > 600 ng/ml (HR 2.9, 95 % CI 1.5–5.5, p

Die technische Kombination von SPECT-Scannern (Single-Photon-Emissions-Computertomografie) mit der Rontgen-Computertomografie (CT) war eine wichtige Innovation auf dem Gebiet der nuklearmedizinischen Hybridbildgebung. Diese Gerate ermoglichen die simultane Darstellung von praziser anatomischer Struktur und funktioneller Bildgebung. Die multimodale Bildgebung mittels SPECT/CT verbessert die Sensitivitat und Spezifitat der nuklearmedizinischen Diagnostik bei verschiedenen klinischen Fragestellungen, die in dieser Ubersichtsarbeit vorgestellt werden.

1. Which renal disorder can be studied by nuclear medicine techniques? (a) Impotence (b) Mass lesion (c) Residual urine (d) All of the above 2. Renal scintigraphy is performed with 99mTc-DTPA and 99mTc-DMSA. The 99mTc-DTPA scan is unremarkable, but a poor uptake in the kidneys is reported on the 99mTc-DMSA scan. What is the most probable diagnosis? (a) Diabetic nephropathy (b) Chronic renal failure (c) Tubulointerstitial disease (d) Acute renal failure

1. What is the gold standard diagnostic test for cardiac transplant rejection? (a) PET (b) 123I-IPPA (c) MRI (d) Endomyocardial biopsy 2. All of the following radionuclide imaging methods are examined for the diagnosis of cardiac transplant rejection EXCEPT: (a) 99mTc-annexin V (b) Radiolabeled somatostatin analog (c) 111In-antimyosin (d) 11C-MQNB

1. All drugs may enhance uptake by altering the biokinetics of the radiopharmaceutical EXCEPT: (a) β-Adrenergic blocking agents (b) Vasodilator drugs (c) Calcium channel-blocking drugs (d) Sympathomimetic agents 2. Which radionuclide does NOT emit alpha particles in targeting radiotherapy? (a) 213Bi (b) 225Ac (c) 211At (d) 114mIn 3. Which of the palliative bone radionuclides has the lowest beta mean range? (a) 32P (b) 188Re (c) 153Sm (d) 89Sr 4. Which of the following radionuclides is considered group 1 “targeting therapy”? (a) 211Astatine (b) 131Cesium (c) 90Yttrium (d) 67Ga

1. In blood–brain barrier imaging: (a) Longitudinal sinuses reveal a higher tracer uptake than the brain. (b) Transverse sinuses reveal a higher tracer uptake than the brain. (c) Blood–brain barrier imaging is performed by 99m-pertechnetate, 99mTc-DTPA, and 99mTc-glucoheptonate. (d) All of the above. 2. Which of the following is NOT a characteristic of the blood–brain barrier (BBB)? (a) High ionic permeability. (b) Existence of Na/K pump. (c) Low nonelectrolyte hydrophilic permeability. (d) It is a tight connection of endothelial cells. 3. Which of the following is a determinant of the transport of lipophilic agents from the blood–brain barrier (BBB)? (a) Na/K pump. (b) Calcium pump. (c) Glycoprotein pump. (d) The cerebral entry of lipophilic agents occurs without any intervention. 4. Which of the following factors is the least important in the permeability of the blood–brain barrier? (a) Lipophilicity. (b) Osmotic pressure. (c) Protein binding. (d) Hydrostatic pressure. 5. Which of the following patterns of BBB imaging in neonates with asphyxia indicates high brain involvement? (a) Typical stroke pattern of uptake in one of the large cerebral arteries. (b) Abnormal uptake in the intermediary region of large cerebral arteries. (c) Skull cap-like increase in uptake. (d) Abnormal focal uptake in the basal ganglia.

[99mTc]Tc-Sestamibi (MIBI) is an increasingly used tool for evaluation of thyroid nodules. However, there is a lack of evidence about the accuracy of this method in the European population. The aim of this study was to assess the utility of MIBI for the differentiation of thyroid nodules in a large cohort. 161 patients underwent MIBI, followed by a thyroidectomy. We used a dual phase MIBI protocol. Interpretation of the images included a scoring system from 0 (absent) to 3 (increased); this was to provide a scale for the uptake of the thyroid nodule in comparison to the paranodular tissue. Additionally, we evaluated the tracer uptake trend in late images compared to early images. We used the final histopathology as the reference standard. Scores 0-1 in early images, scores 0-2 in late images, and an absence of increasing uptake in the thyroid nodule in late images, showed the best predictive values to exclude malignancy, respectively (negative predictive value (NPV) 89%). Highest sensitivity (91%) for malignant nodules was evident in early images with a score 1-3. Highest specificity (91%) was obtained when the negative was defined as an absence of uptake-increase, in the late images. This study confirms that the most valuable feature of MIBI is the high NPV. Thus, with the appropriate interpretation method, high sensitivity and specificity, and moderate PPV can be obtained.

The tumor proliferation marker, Ki-67 index, is a well-established prognostic marker in gastroenteropancreatic neuroendocrine neoplasms (NENs). Noninvasive molecular imaging allows whole-body metabolic characterization of metastatic disease. We investigated the prognostic impact of 18F-FDG PET in inoperable multifocal disease. Methods: Retrospective, dual-center analysis was performed on 89 patients with histologically confirmed, inoperable metastatic gastroenteropancreatic NENs undergoing 18F-FDG PET/CT within the staging routine. Metabolic (PET-based) grading was in accordance with the most prominent 18F-FDG uptake (reference tumor lesion): mG1, tumor-to-liver ratio of maximum standardized uptake value ≤ 1.0; mG2, 1.0–2.3; mG3, >2.3. Other potential variables influencing overall survival, including age, tumor origin, performance status, tumor burden, plasma chromogranin A (≥600 μg/L), neuron-specific enolase (≥25 μg/L), and classic grading (Ki-67–based) underwent univariate (log-rank test) and multivariate analysis (Cox proportional hazards model), with a P value of less than 0.05 considered significant. Results: The median follow-up period was 38 mo (95% confidence interval [CI], 27–49 mo); median overall survival of the 89 patients left for multivariate analysis was 29 mo (95% CI, 21–37 mo). According to metabolic grading, 9 patients (10.2%) had mG1 tumors, 22 (25.0%) mG2, and 57 (64.8%) mG3. On multivariate analysis, markedly elevated plasma neuron-specific enolase (P = 0.016; hazard ratio, 2.9; 95% CI, 1.2–7.0) and high metabolic grade (P = 0.015; hazard ratio, 4.7; 95% CI, 1.2–7.0) were independent predictors of survival. Conclusion: This study demonstrated the feasibility of prognostic 3-grade stratification of metastatic gastroenteropancreatic NENs by whole-body molecular imaging using 18F-FDG PET.

Outcome analyses for patients with gastroenteropancreatic neuroendocrine tumors (GEP NET) after peptide receptor radionuclide therapy (PRRT) are still limited, especially with regard to the impact of the Ki-67 index. Using a single-center analysis, we aimed to establish predictors of survival.We retrospectively analyzed a consecutive cohort of 74 patients who had metastatic GEP NET and underwent PRRT with (177)Lu-octreotate (mean activity of 7.9 GBq per cycle, aimed at 4 treatment cycles at standard intervals of 3 mo). Patients (33 with pancreatic NET and 41 with nonpancreatic GEP NET) had unresectable metastatic disease graded as G1 or G2 (G1/G2) and documented morphologic or clinical progression within less than 12 mo or uncontrolled disease under somatostatin analog treatment. Responses were evaluated according to modified Southwest Oncology Group criteria. Potential predictors of survival were analyzed with the Kaplan-Meier curve method (log-rank test) and multivariate analysis (P0.05).The response rates were 36.5% partial response, 17.6% minor response, 35.1% stable disease, and 10.8% progressive disease for the entire cohort; 54.5% partial response, 18.2% minor response, 18.2% stable disease, and 9.1% progressive disease for pancreatic NET; and 22.0% partial response, 17.1% minor response, 48.8% stable disease, and 12.2% progressive disease for nonpancreatic GEP NET. The median progression-free survival and overall survival were 26 mo (95% confidence interval, 18.3-33.7) and 55 mo (95% confidence interval, 48.8-61.2), respectively. Besides the Ki-67 index, a Karnofsky performance score of less than or equal to 70%, a hepatic tumor burden of greater than or equal to 25%, and a baseline plasma level of neuron-specific enolase of greater than 15 ng/mL independently predicted shorter overall survival (hazard ratio, 2.1-3.1). Patients with a Ki-67 index of greater than 10% still had median progression-free survival and overall survival of 19 and 34 mo, respectively.The results of this study demonstrated the favorable response and long-term outcome of patients with G1/G2 GEP NET after PRRT. Independent predictors of survival were the Ki-67 index, the patient's performance status (Karnofsky performance scale score), the tumor burden, and the baseline neuron-specific enolase level. Even patients with a Ki-67 index of greater than 10% seemed to benefit from PRRT, with a good response and a notable long-term outcome. We present the first evidence, to our knowledge, that even in patients with metastatic disease the distinction between G1 and G2-in particular, between G1 (Ki-67 index of 1%-2%) and low-range G2 (Ki-67 index of 3%-10%)-provides prognostic stratification.

Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine-allowing only approximate estimates of GFR-the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement.Nephrotoxicity was analysed using (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with (177)Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by (99m)Tc-DTPA clearance versus serum creatinine.The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m(2) per year, relative yearly reduction -1.8 ± 18.9%). Fifteen patients (21%) experienced a mild (2-10 ml/min/m(2) per year) and 16 patients (22%) a significant (10 ml/min/m(2) per year) decline of GFR following PRRT. However, 11 patients (15%) showed an increase of10 ml/min/m(2) per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3%) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15% of the assessments and led to underestimation in 12% of patients. None of the investigated factors including cumulative administered activity contributed to the decline of renal function.Serious nephrotoxicity after PRRT with (177)Lu-octreotate is rare (1.3%). However, slight renal impairment (GFR loss2 ml/min/m(2) per year) can frequently (43%) be detected by (99m)Tc-DTPA clearance assessments. Cumulative administered activity of (177)Lu-octreotate is not a major determinant of renal impairment in our study.

Reported experience with systemic (131)I-metaiodobenzylguanidine ((131)I-MIBG) therapy of neuroendocrine tumors comprises different dosing schemes. The aim of this study was to assess the long-term outcome and toxicity of treatment with 11.1 GBq (300 mCi) of (131)I-MIBG per cycle.We performed a retrospective review of 31 patients with advanced metastatic neuroendocrine tumors (20 with carcinoid tumors and 11 with other tumors) treated with (131)I-MIBG. Treatment outcome was analyzed for patients with carcinoid tumors (the most common tumors in this study), and toxicity was analyzed for the entire patient cohort (n = 31). Treatment comprised 11.1 GBq (300 mCi) per course and minimum intervals of 3 mo. The radiographic response was classified according to modified Response Evaluation Criteria in Solid Tumors. Toxicity was determined according to Common Terminology Criteria for Adverse Events (version 3.0) for all laboratory data at regular follow-up visits and during outpatient care, including complete blood counts and hepatic and renal function tests. Survival analysis was performed with the Kaplan-Meier curve method (log rank test; P0.05).The radiographic responses in patients with carcinoid tumors comprised a minor response in 2 patients (10%), stable disease in 16 patients (80%; median time to progression, 34 mo), and progressive disease in 2 patients (10%). The symptomatic responses in patients with functioning carcinoid tumors comprised complete resolution in 3 of the 11 evaluable symptomatic patients (27%), partial resolution in 6 patients (55%), and no significant change in 11 patients. The median overall survival in patients with carcinoid tumors was 47 mo (95% confidence interval, 32-62), and the median progression-free survival was 34 mo (95% confidence interval, 13-55). Relevant treatment toxicities were confined to transient myelosuppression of grade 3 or 4 in 15.3% (leukopenia) and 7.6% (thrombocytopenia) of applied cycles and a suspected late adverse event (3% of patients), myelodysplastic syndrome, after a cumulative administered activity of 66.6 GBq. The most frequent nonhematologic side effect was mild nausea (grade 1 or 2), which was observed in 28% of administered cycles. No hepatic or renal toxicities were noted.Dose-intensified treatment with (131)I-MIBG at a fixed dose of 11.1 GBq (300 mCi) per cycle is safe and offers effective palliation of symptoms and disease stabilization in patients with advanced carcinoid tumors. The favorable survival and limited toxicity suggest that high cycle activities are suitable and that this modality may be used for targeted carcinoid treatment--either as an alternative or as an adjunct to other existing therapeutic options.

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.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 (occurring12 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.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 of45 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.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.

Lobar radioembolization (RE) of the liver can result in reduction in volume of the ipsilateral lobe as well as hypertrophy of the contralateral lobe. Theoretically, hypertrophy of the contralateral liver lobe after RE could increase the chance of a successful liver resection, especially in patients with limited liver function reserve. The aim of this preliminary study was to evaluate the early effects of RE with resin microspheres on the volumes of the liver lobes and spleen. We retrospectively investigated 24 patients (12 women, 44–78 years old) with different types of cancer and liver-dominant metastatic disease who had undergone RE of the liver with resin microspheres. Changes in the volumes of the liver lobes and spleen were quantified by CT before and about 4 to 8 weeks after treatment. Of the 24 patients, 17 suffered from metastases in both liver lobes (group A) and 7 had metastases only in the right liver lobe (group B). The patients in the group A underwent sequential treatment starting with the right liver lobe. The median administered dose was 1.75 GBq. RE was associated with a median increase in volume of the left liver lobe of 34 % (P

Previous radiation therapy of the liver is a contraindication for performing (90)Y microsphere radioembolization, and its safety after internal radiation exposure through peptide receptor radionuclide therapy (PRRT) has not yet been investigated.We retrospectively assessed a consecutive cohort of 23 neuroendocrine tumor (NET) patients with liver-dominant metastatic disease undergoing radioembolization with (90)Y microspheres as a salvage therapy after failed PRRT. Toxicity was recorded throughout follow-up and reported according to Common Terminology Criteria for Adverse Events (version 3). Radiologic (response evaluation criteria in solid tumors), biochemical, and symptomatic responses were investigated at 3 mo after treatment, and survival analyses were performed with the Kaplan-Meier method (log-rank test, P0.05).The median follow-up period after radioembolization was 38 mo (95% confidence interval, 18-58 mo). The mean previous cumulative activity of (177)Lu-DOTA-octreotate was 31.8 GBq. The mean cumulative treatment activity of (90)Y microspheres was 3.4 ± 2.1 GBq, administered to the whole liver in a single session (n = 8 patients), in a sequential lobar fashion (n = 10 patients), or to only 1 liver lobe (n = 5 patients). Only transient, mostly minor liver toxicity (no grade 4) was recorded. One patient (4.3%) developed a gastroduodenal ulcer (grade 2). The overall response rates for radiologic, biochemical, and symptomatic responses were 30.4%, 53.8%, and 80%, respectively. The median overall survival was 29 mo (95% confidence interval, 4-54 mo) from the first radioembolization session and 54 mo (95% confidence interval, 47-61 mo) from the first PRRT cycle. A tumor proliferation index Ki-67 greater than 5% predicted shorter survival (P = 0.007).Radioembolization is a safe and effective salvage treatment option in advanced NET patients with liver-dominant tumor burden who failed or reprogressed after PRRT. The lack of relevant liver toxicity despite high applied (90)Y activities and considerable previous cumulative activities of (177)Lu-octreotate is noteworthy and disputes internal radiation exposure by PRRT as a toxicity risk factor in subsequent radioembolization.

Selection of candidates for peptide receptor radionuclide therapy (PRRT) is increasingly based on receptor positron emission tomography (PET) imaging, including the common tracer 68Ga DOTATOC. However, no studies have yet compared standardized uptake values (SUVs) and absorbed doses in this field.We retrospectively analyzed a consecutive cohort of 21 patients with 61 evaluable tumor lesions undergoing both pretherapeutic 68Ga DOTATOC-PET/CT (Biograph Duo [Siemens Medical Solutions, Erlangen, Germany]; PET acquisition, 75.3 ± 15.4 minutes postinjection; 117.3 ± 33.9 MBq 68Ga DOTATOC) and PRRT with Lu octreotate (7.47 ± 1.39 GBq; intratherapeutic tumor dosimetry with serial whole-body scans; 1, 2, and 4 days postinjection) at our institution. SUVs were compared with the tumor-absorbed doses per injected activity (D/A0) of the subsequent first treatment cycle.The correlation of SUV and D/A0 was r = 0.72 (SUVmean) and r = 0.71 (SUVmax), both P0.001. Pancreatic origin and hepatic localization were associated with higher D/A0, and chromogranin A level and Ki-67 index had no influence on SUV or D/A0. High-SUV lesions (SUVmean15; SUVmax25) resulted in high D/A0 (10 Gy/GBq) in 66.7% to 70.8% and low D/A0 (5 Gy/GBq) in only 8.3% to 12.5% on subsequent PRRT. The mentioned low D/A0 range, on the other hand, was achieved by all lesions with SUVmean7 or SUVmax9.Somatostatin receptor PET imaging may predict tumor-absorbed doses. The ability to indicate insufficient target irradiation by a low SUV could aid in selection of appropriate candidates for PRRT. However, larger series are needed to confirm and validate these initial findings.

Seit einigen Jahren steht mit der kombinierten SPECT-CT des Knochens ein neues Verfahren zur Verfugung, welches die hohe raumliche Auflosung der CT mit der hohen Sensitivitat der Knochen-SPECT verbindet. Hierdurch ist es moglich, gerade bei komplexen anatomischen Strukturen akute schmerzhafte Zustande exakt zu lokalisieren und somit auch einem gezielten operativen Eingriff zuganglich zu machen. Dies spielt insbesondere bei Erkrankungen des Fuses eine Rolle. Im Rahmen dieser Arbeit werden Erkrankungen wie Arthrodese, Infekt, akzessorische Knochen und die tarsale Koalition abgehandelt. Anhand von Fallbeispielen lasst sich die diagnostische Aussagekraft der SPECT-CT darstellen.

Sentinel lymph node biopsy (SLNB) is a widely accepted procedure to accurately stage melanomas with a thickness ≥1 mm. The value of SLNB in thin melanomas is still controversial, especially because long-term observations of these patients are rare. The purpose of the current study was to identify the positive sentinel lymph node (SLN) ratio in low-risk patients with cutaneous melanoma (CM) of thickness less than 1 mm and its possible prognostic value, focusing on long-term follow-up data.In a retrospective single-centre study performed at the Department of Dermatology and Allergy, University of Bonn, 121 patients who had received SLNB were identified out of 621 patients with a diagnosis of CM of1.00 mm thickness presenting between September 2000 and February 2009 (mean follow-up time, 50.9 months).Of the 121 patients, 5 (4.1%) had a positive SLN. All positive SLNs were found in patients with a tumour thickness between 0.90 mm and 1.00 mm. There were no significant differences in the presence of positive SLNs according to Clark level and ulceration status (Clark levels II and III and no ulceration vs. Clark levels IV and V or ulceration), regression, gender or age. Disease-free survival was 100% in the SLN-positive patients. On the other hand, five SLN-negative patients (4.1%) developed disease progression. One of these five progressive patients showed recurrence in the former negative SLN basin (16.7% false-negative rate).A positive SLN in thin melanomas is uncommon with a prevalence of 4.1% in our study population. We could not identify reliable clinicopathological risk factors which could predict results of SLNB in thin melanomas. Based on our results, SLNB may be considered in patients with a melanoma of thickness in the range 0.90-0.99 mm, because all SLN-positive patients belonged to this subgroup.

The incidence of hepatocellular carcinoma (HCC) is worldwide sharply on the rise and patients with advanced disease carry a poor prognosis. HCC is the sixth most common cancer and the third leading cause of cancer associated deaths in the world. Intra-arterially administered 131 I-Lipiodol is selectively retained by hepatocellular carcinomas, and has been used as a vehicle for delivery of therapeutic agents to these tumours. In this review we focus on the therapeutic indications, usefulness and methods of treatment with 131-Iodine Lipiodol. The effectiveness of 131 I-Lipiodol treatment is proven both in the treatment of HCC with portal thrombosis and also as an adjuvant to surgery after the resection of HCCs. It is at least as effective as chemoembolization and is tolerated much better. Severe liver dysfunction represents theoretic contraindication for radioembolization as well as for TACE. In such cases 131 I-Lipiodol is an alternative therapy option especially in tumours smaller than 6 cm.

Purpose Unwanted deposition of 90Y microspheres in organs other than the liver during radioembolization of liver tumours may cause severe side effects such as duodenal ulcer. The aim of this study was to evaluate the significance of posttherapy bremsstrahlung (BS) SPECT/CT images of the liver in comparison to planar and SPECT images in the prediction of radioembolization-induced extrahepatic side effects.Methods A total of 188 radioembolization procedures were performed in 123 patients (50 women, 73 men) over a 2-year period. Planar, whole-body and BS SPECT/CT imaging were performed 24 h after treatment as a part of therapy work-up.Any focally increased extrahepatic accumulation was evaluated as suspicious. Clinical follow-up and gastroduodenoscopy served as reference standards. The studies were reviewed to evaluate whether BS SPECT/CT imaging was of benefit.Results In the light of anatomic data obtained from SPECT/CT, apparent extrahepatic BS in 43% of planar and in 52% of SPECT images proved to be in the liver and hence false positive.The results of planar scintigraphy could not be analysed further since 12 images were not assessable due to high scatter artefacts. On the basis of the gastrointestinal (GI)complications and the results of gastroduodenoscopy, true positive,true-negative, false-positive and false-negative results of BS SPECT and SPECT/CT imaging in the prediction of GI ulcers were determined. The sensitivity, specificity, positive and negative predictive values and the accuracy of SPECT and SPECT/CT in the prediction of GI ulcers were 13%, 88%, 8%,92% and 82%, and 87%, 100%, 100%, 99% and 99%,respectively.Conclusion Despite the low quality of BS images, BSSPECT/CT can be used as a reliable method to confirm the safe distribution of 90Y microspheres and in the prediction of GI side effects.

The coexistence of thyroid autonomy (Plummer's disease) and Graves' disease has been termed "Marine-Lenhart syndrome". During the last years, several papers have been published on the development of Graves' disease shortly after radioiodine therapy of Plummer's disease (autonomy). Especially in patients with elevated thyroid antibodies, the incidence of this event is significantly higher after radioiodine therapy of autonomy. A review of the literature dating back to 1911 is discussed in this paper. The original paper published by Marine and Lenhart comes to the conclusion that the two diseases are different expressions of one disease. Looking at the literature, we have to state now that the Marine-Lenhart syndrome has never existed: With Plummer we know now that Plummer's and Graves' disease are different diseases. They may develop in the same patient but independent from each other.

An angiographic evaluation combined with (99m)Tc-macroaggregated albumin (Tc-MAA) scanning should precede the treatment of any selected candidates for radioembolization (RE) of the liver. If the tumours in one liver lobe have not been targeted in the test angiogram, it should be repeated. However, in a few cases treatment of one liver lobe or at least some segments is safe and feasible and performing a repeated test angiogram with Tc-MAA (Re-MAA) in a separate session leads to more radiation exposure and could be time consuming. Our aim was to evaluate the feasibility of concurrent RE of a part of the liver and therapy planning for another region by simultaneous injection of the Tc-MAA and (90)Y-microspheres in two different locations in the therapy session. Tc-MAA and bremsstrahlung (BS) single photon emission computed tomography (SPECT)/CT were performed separately in an effort to distinguish between the distributions of these two different radiopharmaceuticals.RE was combined with a simultaneous second test angiogram of another lobe or segments in the same session in six patients [44-70 years; five women (83%)]. Five patients suffered from colorectal carcinoma (CRC) and one from ovarian cancer. Tc-MAA and BS SPECT/CT were performed for all cases.Post-therapeutic Tc-MAA SPECT/CT showed in all patients only the distribution of Tc-MAA without any detectable BS. Evaluation of (90)Y-microsphere distribution was not always possible in the post-therapeutic BS scan performed 24 h later due to remaining Tc-MAA radiation. However, scans performed at 48 h post-intervention no longer showed any Tc-MAA "contamination".Combining RE and Re-MAA is feasible in appropriately selected patients.

A 24-year-old man with extraosseous Ewing sarcoma in the pelvis underwent a triphasic bone scintigraphy to rule out bone metastases and local bone infiltration before chemotherapy. The bone scintigraphy showed tracer uptake in the tumor in all 3 phases.

Tc-MAA uptake in the portal vein tumor thrombus may be a predictor of a favorable response to radioembolization. We report here 2 patients with hepatocellular carcinoma and massive intrahepatic and extrahepatic tumor thrombus that showed Tc-MAA uptake in SPECT/CT, who underwent radioembolization with Y resin microspheres. The patients did not experience any adverse effects.

Selective internal radiation therapy (SIRT), a catheter-based liver-directed modality for treating primary and metastatic liver cancer, requires appropriate planning to maximize its therapeutic response and minimize its side effects. 99mTc-macroaggregated albumin (MAA) scanning should precede the therapy to detect any extrahepatic shunting to the lung or gastrointestinal tract. Our aim was to compare the ability of SPECT/CT with that of planar imaging and SPECT in the detection and localization of extrahepatic 99mTc-MAA accumulation and to evaluate the impact of SPECT/CT on SIRT treatment planning and its added value to angiography in this setting. Methods: Ninety diagnostic hepatic angiograms with 99mTc-MAA were obtained for 76 patients with different types of cancer. All images were reviewed retrospectively for extrahepatic MAA deposition in the following order: planar, non–attenuation-corrected SPECT, and SPECT/CT. Review of angiograms and follow-up of patients with abdominal shunting served as reference standards. Results: Extrahepatic accumulation was detected by planar imaging, SPECT, and SPECT/CT in 12%, 17%, and 42% of examinations, respectively. The sensitivity for detecting extrahepatic shunting with planar imaging, SPECT, and SPECT/CT was 32%, 41%, and 100%, respectively; specificity was 98%, 98%, and 93%, respectively. The respective positive predictive values were 92%, 93%, and 89%, and the respective negative predictive values were 71%, 73%, and 100%. The therapy plan was changed according to the results of planar imaging, SPECT, and SPECT/CT in 7.8%, 8.9%, and 29% of patients, respectively. Conclusion: In pre-SIRT planning, 99mTc-MAA SPECT/CT is valuable for identifying extrahepatic visceral sites at risk for postradioembolization complications.

TO THE EDITOR: I read with interest the editorial written by Segall et al. ([1][1]). The authors discuss a combined, multispecialty training “that maintains high standards for nuclear medicine education.” A 3-y residency in nuclear medicine that leads to American Board Nuclear Medicine

The diagnostic accuracy of 18F-FDG-PET (fluoro-2-deoxyglucose-positron emission tomography) remains questionable for primary hepatocellular carcinoma (HCC) but seems to be more promising for restaging and therapy control. Yet, there are no data on FDG-PET in 131I-lipiodol treatment for primary liver cancer. The aim of this study was to relate baseline FDG-PET findings to histologic data and to assess, for the first time, the role of repetitive FDG-PET imaging for follow-up of 131I-lipiodol treatment. Eighteen (18) patients (16 HCC, 2 cholangiocellular carcinoma; CCC) with 36 treatment courses (up to four per patient) had 35 PET exams, including 18 post-treatment follow-up scans in 10 patients (up to three per patient, one without baseline PET; n = 17). Histopathologic results were available in 15 patients. PET results were retrospectively related to histopathologic type, grading, presence of cirrhosis, and tumor size at baseline and compared with computed tomography (CT) during follow-up. Prior to 131I-lipiodol treatment, 8 patients were PET positive and 9 PET negative. Most of the large HCCs were PET positive and most small tumors PET negative (p0.05), despite an overlap below 11 cm. There was no identifiable correlation between PET results and degree of tumor differentiation. Overall, 9 of 10 patients with 17 of 18 follow-up scans showed concordant results with CT. The one discrepant case became PET negative after the first treatment course, despite CT-proven tumor growth (false negative). Patient management was not changed due to PET results. In conclusion, large HCCs were significantly more often PET positive, but there was no correlation with the degree of differentiation. Follow-up PET may be useful if the tumor is first demonstrated to be FDG positive.