EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer.

Radium Ra-223 dichloride (radium-223, Xofigo®) is a targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is the first targeted alpha therapy in this indication providing a new treatment option, with evidence of a significant survival benefit, both in overall survival and in the time to the first symptomatic skeletal-related event. The skeleton is the most common metastatic site in patients with advanced prostate cancer. Bone metastases are a clinically significant cause of morbidity and mortality, often resulting in bone pain, pathologic fracture, or spinal cord compression necessitating treatment. Radium-223 is selectively accumulated in the bone, specifically in areas of high bone turnover, by forming complexes with the mineral hydroxyapatite (the inorganic matrix of the bone). The alpha radiation generated during the radioactive decay of radium-223 produces a palliative anti-tumour effect on the bone metastases. The purpose of this guideline is to assist nuclear medicine specialists in evaluating patients who might be candidates for treatment using radium-223, planning and performing this treatment, understanding and evaluating its consequences, and improving patient management during therapy and follow-up.

Leucocyte scintigraphy with 111In-oxine for assessment of cell trafficking after extracorporeal photopheresis.

Extracorporeal photopheresis (ECP) is an established therapy for transplant rejection, graft-versus-host disease (GvHD) after allogeneic stem cell transplantation, cutaneous T-cell lymphoma and systemic autoimmune disorders such as systemic sclerosis. Knowledge regarding the in vivo behaviour of the cells after reinfusion is very limited. The aim of this prospective study was to investigate the path of 8-MOP-/UVA-exposed radiolabelled cells after ECP treatment and reinfusion. In this prospective single-centre study, peripheral blood mononuclear cells (PBMC) and neutrophils of 10 patients undergoing ECP as part of their regular treatment were labelled separately with (111) In-oxine after exposure to 8-MOP/UVA and prior to reinfusion. The fate of the labelled leucocytes was monitored at 10 min, 3.5 and 24 h following reinfusion with whole-body scintigraphy. Comparison of distribution patterns showed that PBMC and neutrophils have different kinetic patterns after intravenous reinjection. The most prominent difference was immediate retention of PBMC but not of neutrophils in the lungs corresponding to a signal three times more intense. After 24 h, more than 80% of both cell populations could be detected in liver and spleen. By means of a novel tool allowing for tracking of 8-MOP-/UVA-exposed leucocytes in ECP, we could show that organ-specific homing of leucocytes after ECP can be visualized in vivo and that migration patterns differ between PBMC and neutrophils. Based on our results, further studies should (i) extend the morphometric studies described here to specific ECP-responsive conditions and (ii) functionally address the interaction of ECP-modified PBMC with pulmonary tissue in experimental models.

[Joint DGN, OGNMB and SGNM S1 guideline for radiosynoviorthesis]. / Gemeinsame Handlungsempfehlung (S1-Leitlinie) von DGN, OGNMB und SGNM ­ Radiosynoviorthese ­ Stand: 9/2019 ­ AWMF-Registernummer: 031-023.

This recommendation is intended to provide a guideline for radiosynoviorthesis (RSO) in the effective local treatment of chronic inflammatory (non-infectious) joint diseases. It was developed in an interdisciplinary manner and describes the general objectives, definitions, clinical background information, indication and contraindications of this radionuclide therapy. The requirements to be met by a treatment center, the results of pretherapeutic examinations as well as recommendations on how the treatment should be carried out. Here, organizational and technical issues have been considered. Furthermore, information on the surveillance and follow-up of the treated patients can be found. In general, treatment and follow-up should be done in in close cooperation of the participating disciplines.

Treatment of Concurrent Thrombotic Thrombocytopenic Purpura and Graves' Disease: A Report on Two Cases.

Graves' disease (GD) and thrombotic thrombocytopenic purpura (TTP) are autoimmune diseases caused by autoantibodies against the TSH receptor (TRAb) and the enzyme ADAMTS13. We here report on two patients with concurrent GD and TTP, who achieved sustained remission of both conditions with the TTP treatment regimen and thiamazole. Both patients suffered from relapsing TTP and were diagnosed with GD concomitantly at the time of relapse. They were treated with steroids, plasma exchange, rituximab, and thiamazole. This therapy induced complete remission of TTP. TRAb levels also decreased rapidly and both patients developed subclinical hypothyroidism three and five weeks later. Our observations suggest that TTP and GD may be concomitant and that GD possibly triggers a relapse of TTP. The combination of thyrostatic treatment and immunosuppression with PE, rituximab, and steroids is able to induce rapid and prolonged remission of GD.

[Therapy of bone metastases with radium-223. German guidelines]. / Radionuklidtherapie von Knochenmetastasen mittels Radium-223. DGN-Handlungsempfehlung.

This document describes the guideline for therapy of bone metastases with radium-223 ((223)Ra) published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften in Germany (AWMF) under the auspices of the Deutsche Gesellschaft für Nuklearmedizin (DGN), Östereichische Gesellschaft für Nuklearmedizin (OGN), and Schweizerische Gesellschaft für Nuklearmedizin (SGNM). This guidance is based on an interdisciplinary consensus. These recommendations are a prerequisite for the quality management in the treatment of patients with bone metastases from prostate cancer using (223)Ra. They are aimed at guiding nuclear medicine specialists in selecting candidates to receive therapy and to deliver the treatment in a safe and effective manner. The document contains background information and definitions. It covers the rationale, indications and contraindications for therapy with (223)Ra. Essential topics are the requirements for institutions performing the therapy, which patient data have to be available prior to performance of therapy, and how treatment has to be carried out technically and organisationally. Moreover, essential elements of follow-up and aftercare are specified. As a matter of principle, the treatment inclusive aftercare has to be realised in close cooperation with the involved medical disciplines.

2-18fluoro-deoxy-D-glucose positron emission tomography is a reliable predictor for viable tumor in postchemotherapy seminoma: an update of the prospective multicentric SEMPET trial.

PURPOSE: To define the clinical value of 2-18fluoro-deoxy-D-glucose positron emission tomography (FDG PET) as a predictor for viable residual tumor in postchemotherapy seminoma residuals in a prospective multicentric trial. PATIENTS AND METHODS: FDG PET studies in patients with metastatic pure seminoma who had radiographically defined postchemotherapy residual masses were correlated with either the histology of the resected lesion or the clinical outcome documented by computer tomography (CT), tumor markers, and/or physical examination during follow-up. The size of the residual lesions on CT, either >3 cm or < or =3 cm, was correlated with the presence or absence of viable residual tumor. RESULTS: Fifty-six FDG PET scans of 51 patients were assessable. All 19 cases with residual lesions >3 cm and 35 (95%) of 37 with residual lesions < or =3 cm were correctly predicted by FDG PET. The specificity, sensitivity, positive predictive value, and negative predictive value of FDG PET were 100% (95% CI, 92% to 100%), 80% (95% CI, 44% to 95%), 100%, and 96%, respectively, versus 74% (95% CI, 58% to 85%), 70% (95% CI, 34% to 90%), 37%, and 92%, respectively, for CT discrimination of the residual tumor by size (>3 cm/< or =3 cm). CONCLUSION: This investigation confirms that FDG PET is the best predictor of viable residual tumor in postchemotherapy seminoma residuals and should be used as a standard tool for clinical decision making in this patient group.

FDG PET is superior to CT in the prediction of viable tumour in post-chemotherapy seminoma residuals.

AIM: In advanced seminoma the management of residuals after completion of chemotherapy is controversial. Some centres routinely perform surgery for lesions > or =3 cm diameter, others recommend surgery solely if the residual fail to shrink or show even growth. This study prospectively investigates whether FDG PET can improve the prediction of viable tumour in post-chemotherapy seminoma residuals. MATERIALS AND METHODS: After an expansion of a previous study population, 54 patients from eight centres with metastatic seminoma and a CT-documented mass after chemotherapy were included in the study. Six patients were excluded from evaluation because of protocol violations. After PET, the patients underwent either surgery or were followed clinically. On follow-up the lesions were considered to be non-viable when there was unequivocal shrinking, or when the lesion remained morphologically stable for at least 24 months. Any lesion growth was assumed to be malignant. PET results were compared to CT discrimination (< or > or =3 cm) of the residual masses. RESULTS: Fifty-two PET scans were evaluable. After adequate chemotherapy, there were 74 CT-documented residual masses ranging in size from 1 to 11 cm (median, 2.2 cm). Their dignities were confirmed histologically in 13 lesions, or by follow-up CT in 61 lesions. Four of forty-seven lesions <3 cm and 11/27 lesions > or =3 cm were viable. PET was true positive in one lesion <3 cm and in 11 lesions > or =3 cm, false negative in three lesions <3 cm, and true negative in 59 lesions (43 lesions <3 cm). No PET scan was false positive. In detecting viability the sensitivity and specificity was 73% (95% CI, 44-88), and 73% (59-83), respectively, for CT (< or > or =3 cm); and 80% (51-95), and 100% (93-100), respectively, for PET (specificity, P < 0.001). CONCLUSION: In post-chemotherapy seminoma residuals, a positive PET is highly predictive for the presence of viable tumour. The specificity of PET is significantly higher than that of CT when using a > or =3 cm cut-off. A negative PET scan is excellent for the exclusion of disease in lesions > or =3 cm, with a somewhat higher sensitivity than CT (n.s.). PET can contribute to the management of residual seminoma lesions, especially in terms of avoiding unnecessary additional treatment for patients with lesions > or =3 cm.

Imaging of advanced neuroendocrine tumors with (18)F-FDOPA PET.

UNLABELLED: Nuclear medicine plays an important role in the imaging of neuroendocrine tumors (NETs). Somatostatin receptor scintigraphy (SRS) with (111)In-labeled somatostatin receptor analogs is a standard procedure for the detection and staging of NET. Based on the ability of NETs to store biogenic amines, this study evaluated whether 6-(18)F-fluoro-L-DOPA ((18)F-FDOPA) is a suitable PET tracer for NETs. METHODS: Twenty-three patients with histologically verified NETs in advanced stages were consecutively enrolled in the study. All patients underwent PET with (18)F-FDOPA, CT, and SRS within 6 wk. In patients with discrepancies between nuclear medicine and radiologic methods, follow-up investigations were performed by CT, MRI, and ultrasound. (18)F-FDOPA PET with attenuation correction was done 30 and 90 min after injection from the neck to the upper legs. SRS was performed with (111)In-DOTA-D-Phe(1)-Tyr(3)-octreotide at 6 and 24 h. All images were read without knowledge of the results of the other modalities. In every patient, the following regions were evaluated separately: bones, mediastinum, lungs, liver, pancreas, and others, including the abdominal and supraclavicular lymph nodes, spleen, and soft- tissue lesions. The findings were confirmed by clinical examination. The nuclear medicine methods were compared against morphologic imaging, which was considered as gold standard. RESULTS: The most frequently involved organs or regions were the liver (prevalence, 70%) and bone (52%), followed by mediastinal foci (31%), the lungs (22%), and the pancreas (13%). Fifty-two percent of patients had various lymphatic lesions. (18)F-FDOPA was most accurate in detecting skeletal lesions (sensitivity, 100%; specificity, 91%) but was insufficient in the lung (sensitivity, 20%; specificity, 94%); SRS yielded its best results in the liver (sensitivity, 75%; specificity, 100%); however, it was less accurate than PET in all organs. In about 40%, initial CT failed to detect bone metastases shown by PET that were later on verified by radiologic follow-up. CONCLUSION: (18)F-FDOPA PET performs better than SRS in visualizing NETs and may even do better than CT for bone lesions. SRS is essential to establish the usefulness of therapy with somatostatin analogs, yet is less accurate than (18)F-FDOPA PET for staging.

Longitudinal analysis of perfusion lung scintigrams of patients with unoperated chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is the result of single or recurrent pulmonary thromboemboli that are thought to develop into organized pulmonary arterial obstructions by recurrent embolism and in situ thrombosis. Radioisotopic ventilation-perfusion scanning (V/Q scan) is a safe and highly sensitive test for pulmonary thromboembolic disease. The aim was to assess the natural history of thrombus expansion. We performed a prospective quantitative evaluation of ventilation/perfusion scintigrams (V/Q scans) in 20 patients with severe unoperated CTEPH. The baseline V/Q scan of each patient served as a reference for the second scan 21.7 +/- 8.2 months later. Planar images with intravenous 99mTc-labeled human albumin macroaggregates were reconstructed in six standard projections. Perfusion scans were analyzed by a semi-quantitative evaluation. In parallel, hemodynamics and clinical condition were prospectively observed. Lung perfusion scintigrams analyzed by a semi-quantitative method in patients with severe unoperated CTEPH show an apparent decrease of segmental flow abnormalities over time, paralleling right ventricular decline.

Myocardial involvement in a patient with Burkitt's lymphoma mimicking hypertrophic cardiomyopathy.

Burkitt's lymphoma is a highly aggressive type of non-Hodgkin's lymphoma frequently associated with extranodal or abdominal manifestations. We report the case of a young woman with generalized Burkitt's lymphoma, initially presenting with signs and symptoms of central nervous system involvement. Myocardial infiltration mimicking hypertrophic cardiomyopathy was detected with electrocardiogram, echocardiography, magnetic resonance imaging, and positron emission tomographic scintigraphy with F-18 desoxy-glucose. These abnormalities resolved after high-intensity chemotherapy with a modified B-cell acute lymphoblastic leukemia (B-ALL) protocol.

Uptake of indium-111-labeled human polyclonal immunoglobulin G in pancreatic cancer: in vivo and in vitro studies.

Radiolabeled human non-specific polyclonal immunoglobulin G (HIG), is used for the diagnosis of inflammation/infection. Focal uptake of HIG in malignant lesions has also been reported. We investigated the diagnostic value of In-111-HIG in patients with known pancreatic cancer. Fourteen consecutive patients with histologically verified pancreatic cancer were included in this prospective study. Four of them had undergone potentially curative surgery for their primary cancer. Eight patients had liver metastases. Planar and SPECT images of the abdomen were performed after administration of In-111-HIG (74-92 MBq). Scintigraphic results were compared to conventional imaging by means of CT scanning. In addition, In-111-HIG uptake was investigated in a panel of four representative human pancreatic cancer cell lines. Primary pancreatic tumors were visualized by In-111-HIG in 6 out of 10 patients (sensitivity 60%), while 1 was false positive. In comparison, CT scanning was true positive in 9 out of 10 patients (sensitivity 90%), and no false positive. Visualization of liver lesions by means of In-111-HIG was possible in 6 out of 8 patients (sensitivity 75%), while 1 was false positive. In vitro studies revealed only minimal uptake of In-111-HIG into cells (about 3% of activity). Our data demonstrate that In-111-HIG is able to visualize pancreatic primary cancers as well as liver metastases. However, the minimal uptake into tumor cells, as shown in vitro, suggests non-specific tumor related inflammatory reactions, increased vascular permeability, release of indium from In-111-DTPA-labeled antibody and local retention to be responsible for visualization of the tumor site.

Technetium-99m-tetrofosmin scintigraphy in patients with metastatic soft tissue sarcoma.

The lipophilic cationic compound Tc-99m-tetrofosmin has been demonstrated to be a valuable tool for the detection of a variety of tumours. Tc-99m-tetrofosmin uptake by sarcomas in vitro as well as in primary tumours has been reported. Data on the visualisation of metastatic soft tissue sarcomas using this tracer are missing so far. Ten consecutive patients with histopathologically verified metastatic soft tissue sarcoma were included in the present study. Five patients had previously received cytotoxic treatment, the other five patients were chemonaive. All patients underwent whole body planar examination after administration of 500-550 MBq Tc-99m-tetrofosmin, and in case of lung metastases on CT scan, SPECT images were carried out. Non-physiological accumulation of the tracer was considered as a positive result. Scintigraphic results were compared to conventional imaging by means of MRI/CT scanning. Visualisation of distant metastases was achieved in five patients all of whom were chemonaive, while in the chemotherapeutically pretreated patient group (n=5) false negative results were seen. Progressive disease was confirmed by follow-up in all patients. Pulmonary metastases were visualised only in SPECT acquisition and not on planar images. In one patient with diffuse bone marrow infiltration (inflammatory myofibroblastic sarcoma) Tc-99m-tetrofosmin scintigraphy was positive, while CT showed a negative result. According to our results, detection of metastatic soft tissue sarcomas by Tc-99m-tetrofosmin scintigraphy was strongly dependent on the history of previous treatment of the patient. A positive finding before initiation of chemotherapy was not indicative for subsequent therapeutic response. In the staging of chemonaive patients with metastatic soft tissue sarcoma Tc-99m-tetrofosmin may provide some additional information.

Leukocyte scintigraphy with 99mTc-exametazime-labeled leukocytes is not useful for follow-up of systemic vasculitis.

BACKGROUND: The prognosis of systemic vasculitis, for instance Wegener's granulomatosis (WG), was greatly improved by the introduction of immunosuppressive treatment. However, relapses are frequent and predictors are scarce. 111In-leukocytes have been found to indicate unknown manifestations of WG and to predict later relapse. We prospectively investigated the value of 99mTc-Exametazime (99mTc-HMPAO)-labeled leukocytes with regard to specific patterns and for their usefulness in the follow-up of patients with WG. METHODS: The vasculitis group consisted of 8 patients with WG and 2 with idiopathic necrotizing glomerulonephritis (ING). Seven patients with different inflammatory diseases served as controls. Leukocyte labeling with 99mTc-HMPAO was done using a slightly modified Hammersmith protocol. Cell viability after labeling was verified in vivo by the exclusion of early lung and splenic uptake and in vitro by means of propidium iodide and FACS analysis. Static gamma camera images from the head, chest, abdomen, and pelvis were obtained up to 18 hours after injection of approximately 300 MBq 99mTc-HMPAO-labeled leukocytes. Scintigrams were analyzed visually; for semiquantitative analysis ROIs were drawn over the nasal region, the right lung, kidneys, and liver. RESULTS: Increased nasal leukocyte accumulation was found in 7/8 patients with WG and in 2/2 patients with ING. Of 2 patients who had a relapse 6 months later, one presented with, and one without nasal uptake. The kidney/liver ratio was higher in controls (0.24 +/- 0.07 vs. 0.37 +/- 0.11, p < 0.05). Distinct to moderate lung uptake was observed in 2 patients with WG and in one with ING. No correlation was found between scintigraphic results, medication, ANCA status or cretinine levels. CONCLUSION: Nasal leukocyte accumulation is increased in systemic vasculitis, independent of the immunosuppressive treatment and later clinical course. However, this finding is not specific for vasculitis. 99mTc-HMPAO leukocyte scintigraphy failed to indicate or exclude a later relapse and is therefore not suitable as a diagnostic tool in the management of patients with systemic vasculitis.

Intraoperative tissue fluorescence using 5-aminolevolinic acid (5-ALA) is more sensitive than contrast MRI or amino acid positron emission tomography ((18)F-FET PET) in glioblastoma surgery.

OBJECTIVE: The sensitivity of 5-aminolevolinic acid (5-ALA) in detecting intraoperative glioblastoma (GBM) tissue compared to postoperative (18)F-fluoroethyl-L-tyrosine and T1 contrast uptake of tumor cells in positron emission tomography (PET) and magnetic resonance imaging (MRI) scans was investigated in a retrospective image correlative study. METHODS: Ten patients with histological verified GBM in eloquent brain regions underwent 11 surgeries with neuronavigation and 5-ALA assisted tumor resection. Residual 5-ALA fluorescence was labeled intraoperatively on the navigation MRI scans and images were fused with postoperative (18)F-FET PET and T1 contrast MRI. RESULTS: Intraoperatively, at the end of save resection, in all patients 2-5 faint 5-ALA positive resection planes were detected (mean 3·6), compared to 0-4 (18)F-FET positive resection planes (mean 1·4) and 0-2 positive T1 contrast MRI resection planes in postoperative scans. The difference between the number of 5-ALA and (18)F-FET positive resection planes was statistically significant (P = 0·0002). The histological investigation of 5-ALA positive resection margins demonstrated infiltrative tumor in every case. Residual 5-ALA fluorescence on resection margins and postoperative (18)F-FET uptake areas or residual contrast T1 areas were colocalized in all cases, documented by pre-/postoperative image fusion. CONCLUSION: Residual faint 5ALA uptake is documented in large areas at the end of GBM resection and corresponds to tumor infiltration. These 5-ALA positive resection plans exceeded the (18)F-FET uptake areas in postoperative PET scans. Thus, intraoperative 5-ALA residual fluorescence seems to be a more sensitive marker than (18)F-FET PET for residual tumor in malignant gliomas.

PET in testicular cancer.

Testicular cancer is a rare tumor, subdivided into seminomatous and nonseminomatous tumors. Whereas there are no serum tumor markers in the first group, they are present in nonseminomatous tumors, and are also important prognostic factors. Overall, the prognosis for testicular cancers is good, which makes the choice of accurate treatment intensity between under- and overtreatment often difficult. Residual masses in advanced clinical stages occur frequently but are nonvital tissue. PET with F-18 FDG has no defined role in imaging of primary tumors where CT is the first-choice imaging modality. For assessing the success of chemotherapy in the presence of residual masses, especially in pure seminoma, F-18 FDG PET is an important tool. In nonseminomatous tumors, it is hampered by the false-negative results in mature teratoma, for which reason false-negative results are a common problem. F-18 FDG PET performs best in predicting relapse in seminoma residuals larger than 3 cm. So far, no alternative to F-18 FDG for PET imaging of testicular cancer has been found. PET-CT has not yet been proven to be superior to PET alone in testicular cancer.

Higher frequency of thyroid tumors in the right lobe.

Recently, using ultrasonography, we observed that the right lobe usually is larger compared with the left thyroid lobe. Since the higher cell number in a larger right lobe may confer a higher tumor risk, we investigated the location of benign and malignant lesions to test the hypothesis of a more frequent occurrence in this lobe. In 1,001 consecutive patients with benign thyroid lesions, tumors more frequently occurred in the right lobe (+21.5%, p = 0.0022). Furthermore, in 1,277 thyroid cancer patients with 1,302 thyroid cancers, the right lobe more often harbored the tumor initially (+22.9%, p = 0.0009). Our data show a larger proportion of both benign and malignant tumors in the right thyroid lobe.

Diagnostic imaging in Merkel cell carcinoma: lessons to learn from 16 cases with correlation of sonography, CT, MRI and PET.

OBJECTIVE: The authors report imaging findings in a series of 16 patients with MCC, a rare tumour which is often managed primarily by a dermatologist. To our knowledge, no equivalent series of MCC has been described in the nuclear medicine literature. MATERIAL AND METHODS: In this IRB-approved retrospective noncomparative case series 16 patients with biopsy-proven Merkel cell carcinoma were included between January 1999 and October 2007. Twenty-nine whole body PET scans (18F-FDG n=24, 18F-FDOPA n=5) in 16 patients were retrospectively reviewed with regard to tracer uptake in six anatomical sites per patient. For 127/144 of FDG-PET evaluated regions and 68/144 of regions depicted by conventional imaging methods, a valid standard of reference could be obtained. A combined standard of reference was applied, which consisted of histopathology (lymphadenectomy or biopsy) or clinical or radiological follow-up for at least 12 months. RESULTS: the mean FDG uptake over the clinicopatholigical verified FDG avid areas was 4.7 SUV (1.5-9.9 SUV). The region based assessment of diagnostic value, in consideration of the standard of reference, resulted in a sensitivity of 85.7% and a specificity of 96.2% of FDG-PET (n=127) and in a combined sensitivity of 95.5% and a specificity of 89.1% for morphological imaging methods (n=68). Differences between methods did not reach statistical significance (p=1.00, p=0.18). CONCLUSIONS: FDG-PET is a highly useful whole body staging method of comparable value compared to conventional imaging methods with restricted field of view. The lessons learned from case series are discussed.