[Somatostatin receptor PET/CT (SSTR-PET/CT)]. / Somatostatinrezeptor-PET/CT.

The present guideline is focused on quality assurance of somatostatin receptor PET/CT (SSTR-PET/CT) in oncology patients. The document has been developed by a multidisciplinary board of specialists providing consensus of definitions, prerequisites, methodology, operating procedures, assessment, and standardized reporting. In particular, imaging procedures for the two most commonly used radioligands of human SSTR, i. e. 68Ga-DOTATOC and 68Ga-DOTATATE are presented. Overall, SSTR-PET/CT requires close interdisciplinary communication and cooperation of referring and executing medical disciplines, taking into account existing guidelines and recommendations of the European and German medical societies, including the European Association of Nuclear Medicine (EANM), German Society for Endocrinology (DGE), German Society for Nuclear Medicine (DGN) and German Society for Radiology (DRG).

[PET-CT and PET-MRI of the prostate : From 18F-FDG to 68Ga-PSMA]. / PET-CT/-MRT der Prostata : Von 18F-FDG zu 68Ga-PSMA.

CLINICAL/METHODICAL ISSUE: In the last few years nuclear medical diagnostics have experienced a unprecedented renaissance in the diagnostics of prostate cancer, due to the availability of hybrid imaging with positron emission tomography computed tomography (PET/CT), PET magnetic resonance imaging (PET/MRI) and single photon emission computed tomography (SPECT) CT as well as the development of prostate-specific radiopharmaceuticals. METHODICAL INNOVATIONS: The use of fluorodeoxyglucose (FDG), which has been successfully implemented for many years in PET diagnostics, is only helpful in dedifferentiated tumors due to the biological characteristics of prostate cancer. New specific radiopharmaceuticals, such as choline-derivatives, which are incorporated into the prostate cancer cell and built into the cell membrane as well as the recently developed highly specific ligands for prostate-specific membrane antigen (PSMA) are revolutionizing prostate cancer imaging and (re-) staging. PRACTICAL RECOMMENDATIONS: The 68 Ga-labeled PSMA ligands for PET-CT and PET-MRI are highly specific tracers for primary diagnostics and detection of metastases of prostate carcinoma. In risk patients, which includes patients with intermediate and high-risk tumors, they have largely replaced choline-based PET-CT, especially in the case of very low PSA values <0.5 ng/ml in the diagnostics of recurrence. The use in the primary diagnostics as PET-MRI, also in combination with multiparametric MRI (mpMRI), is promising with respect to early diagnostics and image fusion-assisted biopsy as well as surgery and irradiation planning.

[Bone-specific therapy with radium-223 dichloride : Castration-resistant prostate cancer with symptomatic bone metastases]. / Knochenspezifische Radium-223-Dichlorid-Therapie : Symptomatisches, ossär metastasiertes, kastrationsresistentes Prostatakarzinom.

Radium-223 dichloride (Xofigo®, Alpharadin) is approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. As a calcium mimetic, it is integrated into osteoplastic bone lesions and emits alpha particles with high energy which leads to local destruction of tumor cells. In the 2013 published ALSYMPCA trial, a significant advantage for overall survival and quality of life in comparison to placebo was found. Recent data suggest an increased potential in combination with next generation hormonal treatment.

[Intravesical radioimmunotherapy of carcinoma in situ of the urinary bladder after BCG failure]. / Intravesikale Radioimmuntherapie des Carcinoma in situ der Harnblase nach BCG-Versagen.

BACKGROUND: In failure to respond to bacillus Calmette-Guérin (BCG) in patients with carcinoma in situ (CIS) of the urinary bladder, radical cystectomy remains the mainstay after BCG failure. OBJECTIVES: The aim of this pilot study was to evaluate tolerability and safety of the α­emitter radioimmunoconjugate instillation in patients after BCG failure. MATERIALS AND METHODS: Nine patients were included. After emptying the bladder via a transurethral catheter, Bi-213-anti-EGFR-mAb was instilled. Treatment was terminated by emptying of the radioimmunoconjugate from the bladder 120 min after instillation. Efficacy was evaluated via endoscopy and histology 6 weeks after instillation. RESULTS: All patients showed excellent toleration of the treatment without any side effects. Treatment resulted in complete eradication of tumor cells in 3 patients and persistent tumor detection in the other 6 patients. CONCLUSIONS: Intravesical instillation of Bi-213-anti-EGFR-mAb is a promising therapeutic option for treatment of in situ bladder cancer after BCG failure for patients who wish to preserve the bladder.

[Peptide receptor radionuclide therapy for patients with somatostatin receptor expressing tumours. German Guideline (S1)]. / Peptidrezeptor-Radionuklidtherapie Somatostatinrezeptor-exprimierender Tumore. DGN-Leitlinie (S1).

This document describes the guideline for peptide receptor radionuclide therapy (PRRT) published by the German Society of Nuclear Medicine (DGN) and accepted by the Association of the Scientific Medical Societies in Germany (AWMF) to be included in the official AWMF Guideline Registry. These recommendations are a prerequisite for the quality management in the treatment of patients with somatostatin receptor expressing tumours using PRRT. They are aimed at guiding nuclear medicine specialists in selecting likely candidates to receive PRRT and to deliver the treatment in a safe and effective manner. The recommendations are based on an interdisciplinary consensus. The document contains background information and definitions and covers the rationale, indications and contraindications for PRRT. Essential topics are the requirements for institutions performing the therapy, e. g. presence of an expert for medical physics, intense cooperation with all colleagues involved in the treatment of a patient, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how treatment has to be carried out technically. Here, quality control and documentation of labelling are of great importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with the involved medical disciplines. Generally, the decision for PRRT should be undertaken within the framework of a multi-disciplinary tumour board.

Combined SPECT/CT improves detection of initial bone invasion and determination of resection margins in squamous cell carcinoma of the head and neck compared to conventional imaging modalities.

PURPOSE: Knowledge of the presence and extent of bone infiltration is crucial for planning the resection of potential bone-infiltrating squamous cell carcinomas of the head and neck (HNSCC). Routinely, plain-film radiography, multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are used for preoperative staging, but they show relatively high rates of false-positive and false-negative findings. Scintigraphy with (99m)Tc-bisphosphonate has the ability to show increased metabolic bone activity. If combined with anatomical imaging (e.g. (SPECT)/CT), it facilitates the precise localization of malignant bone lesions. The aim of this study was to analyse the indications and advantages of SPECT/CT compared with standard imaging modalities and histology with regard to specificity and sensitivity METHODS: A longitudinally evaluated group of 30 patients with biopsy-proven HNSCC adjacent to the mandible underwent (99m)Tc-bisphosphonate SPECT/CT, MRI, MSCT and conventional radiography before partial or rim resection of the mandible was performed. Bone infiltration was first evaluated with plain films, MSCT and MRI. In a second reading, SPECT/CT data were taken into account. The results (region and certainty of bone invasion) were evaluated among the different imaging modalities and finally compared with histological specimens from surgical resection as the standard of reference. For a better evaluation of the hybrid property of SPECT/CT, a retrospectively evaluated group of 20 additional patients with tumour locations similar to those of the longitudinally examined SPECT/CT group underwent SPECT, MSCT and MRI. To assess the influence of dental foci on the specificity of the imaging modalities, all patients were separated into two subgroups depending on the presence or absence of teeth in the area of potential tumour-bone contact. RESULTS: Histologically proven bone infiltration was found in 17 patients (57 %) when analysed by conventional imaging modalities. SPECT/CT data revealed bone infiltration in two additional patients (7 %), who both showed discrete cortical bone erosion not visible by MSCT or MRI. There were no false-positive or false-negative findings on SPECT/CT. The quality criteria for detecting bone involvement in HNSCC by SPECT/CT were as follows: sensitivity 100 % (lower 95 % confidence interval limit 80 %), specificity 100 % (75 %), positive predictive value 100 % (80 %) and negative predictive value 100 % (75 %). Corresponding data for MRI were 95 % (76 %), 94 % (73 %), 95 % (76 %) and 94 % (73 %), and for MSCT were 89 % (71 %), 100 % (85 %), 100 % (86 %) and 88 % (69 %). In the retrospective evaluation SPECT showed results similar to SPECT/CT. CONCLUSION: Hybrid SPECT/CT has a high specificity as it can provide additional information about the existence and local extent of malignant bone infiltration of the mandible. Although the sensitivity of conventional SPECT is similar to that of SPECT/CT, the latter provides a much better delineation of the local tumour-bone contact area. Based on this information, surgical intervention of the rim versus partial resection can be planned and performed more precisely. Patient outcome can be improved by avoiding undertreatment and unnecessary or overextended bone resections.

Transferring innovative freehand SPECT to the operating room: first experiences with sentinel lymph node biopsy in malignant melanoma.

PURPOSE: The purpose of this study was to report on the first experiences with freehand single-photon emission-computed tomography (freehand SPECT) in sentinel lymph node biopsy (SLNB) in patients with malignant melanoma. Freehand SPECT is a novel imaging modality combining gamma probes, surgical navigation systems, and emission tomography algorithms, designed to overcome some of the limitations of conventional gamma probes. METHODS: In this study 20 patients with malignant melanoma underwent conventional planar scintigraphy prior to surgery. In the operating room, the number and location of separable SLNs were detected first by a pre-incisional scan with freehand SPECT to render a 3D-image of the target site and afterwards by a scan with a conventional gamma probe. After SLNB another scan was performed to document the removal of all targeted SLNs. RESULTS: Planar scintigraphy identified 40 SLNs in 26 nodal basins. Pre-incisional freehand SPECT mapped 38 of these nodes as well as one additional node in one patient (95.0% node based sensitivity). The results of freehand SPECT were identical to those of planar scintigraphy in 25 basins, while it missed one basin (96.2% basin based sensitivity). In comparison, the gamma probe failed to detect 7 nodes in 4 basins (82.5% node based sensitivity and 84.6% basin based sensitivity). After resection freehand SPECT detected 9 remaining radioactive spots, two of whichwere resected as they matched the position of SLNs detected on preoperative planar scintigraphy. CONCLUSIONS: Freehand SPECT provides a real-time, intraoperative 3D-image of the radioactive labelled SLNs, facilitating their detection and resection.

Positron-emission tomography CT to identify local recurrence in stage I lung cancer patients 1 year after stereotactic body radiation therapy.

PURPOSE: To evaluate the diagnostic value of positron-emission tomography/computed tomography (PET/CT) in stage I lung cancer patients treated with stereotactic body radiation therapy (SBRT), who have suspicious or unclear local recurrence findings in CT 1 year after treatment. PATIENTS AND METHODS: A group of 29 patients with unclear or suspicious CT findings 1 year after SBRT were examined with PET/CT. The ability of standard uptake values (SUVmax, SUVmean and posttherapeutic reduction in SUV) to detect local failure and identify patients at a high risk of disease-specific death was evaluated using logrank statistics. Histology and clinical follow-up were the gold standards for local recurrence. RESULTS: SUVmean greater than 3.44 (p = 0.001); SUVmax greater than 5.48 (p = 0.009) or a relative reduction in SUVmean or SUVmax of less than 43 (p = 0.030) or 52 % (p = 0.025), respectively, was indicative of local recurrence. These parameters also correlated with an increased risk of disease-specific death: SUVmean greater than 2.81 (p = 0.023); SUVmax greater than 3.45 (p = 0.007) or a relative reduction in SUVmean or SUVmax of less than 32 (p = 0.015) or 52 % (p = 0.013), respectively, was indicative of an increased risk of disease-specific death. CONCLUSION: PET/CT performed 1 year after SBRT can reliably identify local recurrence and therefore help to clarify unclear CT findings. As posttherapeutic glucose metabolism also correlates with disease-specific survival, PET/CT may help to stratify lung cancer patients for additional treatment 1 year after SBRT.

First Experiences with Navigated Radio-Guided Surgery Using Freehand SPECT.

BACKGROUND: Sentinel lymph node biopsy (SLNB) in melanoma using one-dimensional gamma probes is a standard of care worldwide. Reports on the performance are claimed by most groups to successfully detect the SLNs during the surgical procedure in almost 100% of the patients. In clinical practice, however, several issues remain which are usually not addressed: the difficulty of intraoperative detection of deeply located nodes, SLN detection in obese patients or in the groin and the impossibility to make a scan of the entire wound after SLN resection to avoid false negative testing for eventually remaining SLNs. MATERIALS AND METHODS: The concept behind freehand SPECT is to combine a gamma probe as used for conventional radio-guided surgery with a tracking system as used in neurosurgical navigation. From this combination and a proper algorithm framework the 3D reconstruction of radioactivity distributions and displaying these intraoperatively is possible. CONCLUSION: In summary, the feasibility of freehand SPECT could be shown and provides an image-guided SLNB and a truly minimally invasive and optimized surgical procedure.

Retrospective web-based multicenter evaluation of ¹8F-FDG-PET and CT derived predictive factors. Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan in follicular non Hodgkin's lymphoma.

AIM: Although predictive factors (PF) for conventional lymphoma therapy are established and frequently used in clinical practice and medical research, the PF for radioimmunotherapy (RIT) have not been fully defined until now. The aim of this multicenter evaluation is to prove the feasibility of the multicenter web-based data collection and to preliminary explore imaging findings and prediction of therapy response in patients with follicular lymphoma (FL) following radioimmunotherapy (RIT) with 90Y-ibritumomab tiuxetan. PATIENTS, METHODS: We retrospectively analyzed and correlated clinical and imaging data (CT and FDG-PET) before and after RIT as documented by the RIT-Network. Evaluation of treatment response was done on both patient and lesion basis. Every measurable lesion was analyzed in terms of standardized uptake value (SUV), volume (CT and PET) and response. PF were identified using a uni- and multivariate model. A web-based system was used for the documentation and evaluation of clinical and imaging data. RESULTS: 16 patients with at least one PET before and after RIT were eligible for analysis. Concerning response three months postRIT, 5 patients achieved a CR, 6 patients a PR and 4 patients remained with NC. A total of 159 lesions were measured (mean 10±8). In the multivariate model the log lesion volume (p < 0.0001), the total (p = 0.03) and maximum lesion volume (p = 0.05) were predictors for response (CR + PR). Concerning the lesional CR initial small lesion volume (p = 0.009) and its high metabolic activity (p = 0.01) were identified as predictors. The web-based system showed no major disturbances allowing secure data transfer and central image interpretation in a reasonable time. CONCLUSION: The use of a web-based multicenter archiving system for clinical and imaging data is technically feasible in a multicenter setting and allows a central analysis. This preliminary analysis suggests that FDG-PET may predict the likelihood of response to RIT.

Diagnostic imaging work up in multi-nodular goiter.

Ultrasound, scintigraphy and sonographically guided fine-needle biopsy are the cornerstones in the diagnostic work-up multinodular goitre. Subsequent decisions for adequate treatments should be based on accurate tests to avoid unnecessary intervention. Especially in areas with endemic goitre a preselection of patients for the most effective procedure e.g. surgical or medical treatment is mandatory. Autoimmune hyperthyroidism (Graves' disease), solitary hyperfunctioning thyroid nodules and toxic multinodular goitre (Plummer's disease) constitute a clear indication for radioiodine treatment in many cases. Recently, there is an emerging role for I-131 in the treatment for so called subclinical hyperthyroidism caused by either of three first entities and for patients with non-toxic goitre, in whom surgery is not an option. These patients with large non toxic goitre encompass a group of patients who are euthyroid but may benefit from diminishment of thyroid volume. We review the spectrum of diagnostic tests and provide some recommendations regarding (nuclear medicine) therapy.

[PET-CT for neuroendocrine tumors and nuclear medicine therapy options]. / PET-CT bei neuroendokrinen Tumoren und nuklearmedizinische Therapiemöglichkeiten.

Neuroendocrine tumors (NET) are defined by biochemical characteristics and structures which can be specifically addressed by radioligands for diagnostic imaging as well as radionuclide therapy in nuclear medicine. Somatostatin receptor imaging has been shown to be an important part of the diagnostic process in the management of NET for a long time. In recent years a number of tracers enabling PET-based imaging of somatostatin receptors and amine precursor uptake have been developed. By combining the specific functional information of the PET signal with anatomical information by CT imaging using PET-CT hybrid scanners, primary tumors and metastases can be detected with high resolution and high sensitivity. Compared with conventional indium-111 octreotide scintigraphy PET-CT has a higher resolution and also a lower radiation exposure. In addition, quantification of the tracer uptake allows therapy monitoring. By labelling with therapeutic beta-emitters, such as lutetium-177 or yttrium-90, a systemic internal radiotherapy with somotostatin analogues (peptide radionuclide radiation therapy, PRRT) can be provided as a therapeutic option for patients with unresectable and metastasized neuroendocrine tumors.

Radio-guided surgery for persistent differentiated papillary thyroid cancer: case presentations and review of the literature.

BACKGROUND AND AIMS: Persistent differentiated papillary thyroid cancer following radical locoregional surgery with metastases is an indication for limited reoperation or radioiodine therapy. Following injection of radioiodine, radio-guided surgery with application of an intraoperative gamma probe offers detection of metastases not seen by conventional imaging and control of completeness of resection. PATIENTS/METHODS: We demonstrate four patients with locoregional metastases, two of them with additional distant metastases of papillary thyroid cancer following radical neck surgery. Postoperative radioiodine scans demonstrated persistent ipsilateral or contralateral cervical and mediastinal lymph node and isolated rib metastases. RESULTS: Radio-guided surgery (RGS) leads to complete clearance of persistent lymph node metastases by limited recurrent neck surgery, resection of metastases not seen by conventional imaging and control of complete mediastinal lymph node dissection. Post-RGS scans allowed early diagnosis of occult diffuse or nodal pulmonary metastases in two patients. At last follow-up, 23 to 48 months following RGS and radioiodine therapy, there was no evidence of disease. CONCLUSIONS: Radio-guided surgery is an additive surgical technique with low morbidity in selected patients with persistent thyroid cancer individualizing tumor therapy options in multimode oncological therapy.

[Scintigraphic procedures in internal medicine--indications, limits, possibilities]. / Szintigraphische Verfahren in der Inneren Medizin -- Indikationen, Grenzen, Möglichkeiten.

Scintigraphy continues to play an important diagnostic role in internal medicine. Many diagnostic questions can only be answered with scintigraphic methods. The application of specific radiopharmaceutical tracers offers the unique possibility to visualize ongoing functional changes, associated with diseases concerning internal medicine. The diagnostic potential of modern scintigraphic procedures such as PET for internal medicine is not yet sufficiently used and will continue to grow with hybrid systems, such as PET-CT and SPECT-CT.

[Reoperation for thyroid cancer]. / Wiederholungseingriffe beim Schilddrüsenkarzinom.

Reoperation for thyroid cancer needs to consider patient-, tumor- and therapy-related aspects as well as present diagnostic results. Reoperation because of thyroid remnants, persistence of the primary tumor and lymph node metastasis (completion surgery) has to be distinguished from reoperation due to locoregional recurrence (primary tumor, lymph nodes). The primary surgical strategy should avoid the need for reoperation. The extent of reoperation is related to the extent of primary surgery, stage, and distant metastasis. The timing and indication of reoperation for differentiated thyroid carcinoma in an interdisciplinary multimodal treatment setting depends on diagnostic radioiodine scans and radioiodine therapy. Long-term, recurrence-free survival is achieved by sufficiently radical surgery with acceptable morbidity, including all additive or adjuvant treatment options.

FDG PET and other imaging modalities in the primary diagnosis of suspicious breast lesions.

Mammography is the primary imaging modality for screening of breast cancer and evaluation of breast lesions (T staging). Ultrasonography is an adjunctive tool for mammographically suspicious lesions, in patients with mastopathy and as guidance for reliable histological diagnosis with percutaneous biopsy. Dynamic enhanced magnetic resonance mammography (MRM) has a high sensitivity for the detection of breast cancer, but also a high false positive diagnosis rate. In the literature, MRM is reported to have a sensitivity of 86-96%, a specificity of 64-91%, an accuracy of 79-93%, a positive predictive value (PPV) of 77-92% and a negative predictive value (NPV) of 75-94%. In unclarified cases, metabolic imaging using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) can be performed. In the literature, FDG PET is reported to have a sensitivity of 64-96%, a specificity of 73-100%, an accuracy of 70-97%, a PPV of 81-100% and an NPV of 52-89%. Furthermore, PET or PET/CT using FDG has an important role in the assessment of N and M staging of breast cancer, the prediction of tumour response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy, and the differentiation of scar and cancer recurrence. Other functional radionuclide-based diagnostic tools, such as scintimammography with sestamibi, peptide scintigraphy or immunoscintigraphy, have a lower accuracy than FDG PET and, therefore, are appropriate only for exceptional indications.

Clinical and diagnostic value of preoperative MR mammography and FDG-PET in suspicious breast lesions.

Dynamic enhanced magnetic resonance (MR) mammography and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) of the breast were directly compared preoperatively in suspicious breast lesions. Forty-two breast lesions in 40 patients were examined with a three-dimensional dynamic MR imaging series and FDG-PET. The MR and PET examinations were evaluated separately and the results were compared with the histological findings. The sensitivity and specificity of each method were calculated. The diagnostic value of both modalities as single diagnostic tool and in combination was investigated. Nineteen malignant and 23 benign breast lesions were proven histologically. Magnetic resonance mammography and FDG-PET showed a sensitivity of 89 and 63%, respectively. The specificity was 74 and 91%, respectively. The combination of both imaging methods decreased the not-required biopsies from 55 to 17%. Only one false-negative finding-a patient pre-treated with chemotherapy-was observed in both methods. The combination of MR mammography and FDG-PET can help to decrease biopsies of benign breast lesions. Because of their high cost, these modalities should only be used in problematic cases to either rule out or to demonstrate malignancy. The best diagnostic strategy is achieved using MR mammography first. If the diagnosis is still questionable, FDG-PET can be performed.