X-ray-determined structure of the technetium complex [Tc2(µ-CO)2(NC5H5)2(CO)6] revisited: [Tc2(µ-OMe)2(NC5H5)2(CO)6] as the correct formulation.

Some of us reported previously the structure of di-µ-carbonyl-bis[tricarbonyl(pyridine)technetium], [Tc2(µ-CO)2(C5H5N)2(CO)6], as the main product of the reaction of [Tc2(CO)10] with pyridine at room temperature, using the reagent itself as solvent [Zuhayra et al. (2008). Inorg. Chem. 47, 10177-10182]. On the basis of an X-ray analysis of the product, a molecular structure was proposed with two bridging carbonyls displaying very unusual geometrical features, not explained at the time. Subsequent chemical considerations, coupled with density functional theory (DFT) calculations, prompted us to revise the original structure determination. Using the original raw diffraction data, we have now performed new refinements to show that the previously proposed `bridging carbonyls' actually correspond to bridging methoxide groups, and that the crystals analyzed at the time therefore would correspond to the complex di-µ-methoxido-bis[tricarbonyl(pyridine)technetium], syn-[Tc2(µ-OMe)2(NC5H5)2(CO)6]. This methoxide-bridged complex likely was a minor side product formed along with the main product in the above reaction, perhaps due to the presence of trace amounts of methanol and air in the reaction mixture.

PSMA-617 inhibits proliferation and potentiates the 177Lu-PSMA-617-induced death of human prostate cancer cells.

The human prostate-specific membrane antigen (PSMA) is substantially up-regulated in metastatic prostate cancer (PCa) cells. PSMA can be targeted by 177Lu conjugated to PSMA-617, a high-affinity ligand for the PSMA. The binding of the radioligand, 177Lu-PSMA-617, results in its internalisation and delivery of ß-radiation into the cancer cells. However, PSMA-617, a component of the final product in the synthesis of the radioligand, may also play a role in the pathophysiology of PCa cells. The present study aimed to clarify the effects of PSMA-617 (10, 50 and 100 nM) on the expression of PSMA in PSMA-positive LNCaP cells, their proliferation, 177Lu-PSMA-617-induced cell death by WST-1 and lactate dehydrogenase assays, immunohistochemistry, western blotting, immunofluorescence staining and uptake of 177Lu-PSMA-617. PSMA-617 at 100 nM concentration induced cell-growth arrest, down-regulated cyclin D1 and cyclin E1 (by 43 and 36%, respectively) and up-regulated the cyclin-dependent kinase inhibitor p21Waf1/Cip1 (by 48%). Immunofluorescence staining demonstrated reduced content of DNA, pointing to a lower rate of cell division. PSMA-617 (up to 100 nM) did not alter the uptake of 177Lu-PSMA-617 into the LNCaP cells. Interestingly, simultaneous treatment with 177Lu-PSMA-617 and PSMA-617 for 24 and 48 h substantially potentiated the cell-death promoting effects of the radioligand. In conclusion, the combination of impeding tumour cell proliferation by PSMA-617 and its potentiation of the radiation-induced cell death brought about by 177Lu-PSMA-617 in PCa cells may considerably improve the outcome of the radiation therapy with 177Lu-PSMA-617, especially in patients with decreased radiosensitivity of PCa cells to the radioligand.

Evaluation of sentinel lymph node localization in malignant melanoma by preoperative semiconductor gamma camera and planar lymphoscintigraphy.

INTRODUCTION: Performing lymphoscintigraphy in a separate room, frees up the conventional gamma camera, coupled with the desire to directly localize sentinel lymph nodes (SLN) in the operating theatre has led to the development of high-resolution semiconductor-detector based handheld gamma-cameras, CrystalCam. METHODS: This work consists of phantom and clinical studies. For the first part, a Jaszczak phantom with hollow spheres of various volumes were filled with the 99m Tc and the camera's sensitivity was measured at various distances to assess the possibilities and limitations of the device. The clinical study evaluates the effectiveness of CrystalCam in localizing SLN in 40 consecutive malignant melanoma patients compared to both conventional planar lymphoscintigraphy and hybrid SPECT/CT. SLNs detected by planar lymphoscintigraphy were marked on the patients' skin using a UV-marker. CrystalCam images were acquired in another room by another examiner and the SLNs were marked with a felt pen. The detected nodes by both camera systems were evaluated using UV-lamp and normal light to visualize the UV- and felt pen marks respectively. The concordance rate of the SLNs and higher-echelon nodes localized by both planar scintigraphy and CrystalCam imaging with respect to the total SLNs and higher-echelon nodes detected by SPECT/CT imaging are compared and statistically analyzed. RESULTS: The results of the phantom study show a good correlation between activity and count-rates for all distancesSPECT/CT, CrystalCamm, and planar lymphoscintigraphy detected 69, 58, and 61 SLNs respectively. The concordance rate of 95.65% by the CrystalCam and planar scintigraphy implies both cameras are statistically coequal in preoperative SLN detection of malignant melanoma. For the higher-echelon nodes, SPECT/CT, planar and CrystalCam imaging systems identified 82, 48, and 13 respectively; thus, CrystalCam was statistically inferior to planar imaging. CONCLUSION: The handheld CrystalCam is a reliable instrument for localizing SLNs in surgical centers without an on-site nuclear medicine department.

[Hyperpolarized 13C magnetic resonance imaging-a window into metabolism : High-resolution images of human metabolism]. / Hyperpolarisierte 13C­Magnetresonanztomographie ­ ein Fenster in den Stoffwechsel : Hochauflösende Darstellung des humanen Metabolismus.

CLINICAL ISSUE: Despite being one of the main pillars of modern diagnostics, magnetic resonance imaging (MRI) uses only a tiny fraction of its potential: no more than a millionth of all nuclear spins contribute to the MRI signal. In order to increase this fraction, called polarization, MRI scanners with stronger magnetic fields are being developed. However, even the most modern scanners do not exploit the potential of MRI. METHODOLOGICAL INNOVATIONS: To make full use of this potential, hyperpolarized MRI (HP-MRI) is an excellent tool: quantum mechanical tricks can be used to generate contrast agents whose nuclear spins can deliver a MRI signal that is up to a 100,000 times stronger. This signal enhancement allows imaging of in vivo processes that would be otherwise impossible to measure. It is particularly interesting to introduce these magnetically labeled nuclei into metabolic processes so that the metabolism can be investigated non-invasively and in vivo. PERFORMANCE: Small but diagnostically important changes in metabolism could be found before macroscopic tissue changes were otherwise visible. High-resolution images can be acquired within a few 100 ms, enabling metabolic monitoring in real-time. Heart, brain, and prostate are among the organs that have already been investigated in over 90 clinical trials using this emerging technology. ACHIEVEMENTS: So far, displaying tissue in a similar manner was only possible using nuclear medicine, e.g., positron emission tomography (PET) utilizing radionuclides and without resolution of various metabolic steps. A change in tumor metabolism following treatment was shown within hours in HP-MRI. These applications coupled with background information about the technology are the subject of this review.

Pre- and intratherapeutic predictors of overall survival in patients with advanced metastasized castration-resistant prostate cancer receiving Lu-177-PSMA-617 radioligand therapy.

BACKGROUND: Systemic Lutetium-177 prostate-specific membrane antigen-617 radioligand therapy (Lu-177-PSMA-617-RLT) is a novel treatment approach in patients suffering from metastasized castration-resistant prostate cancer. Nonetheless, a therapeutic response may fail to appear in a proportion of patients. This study aims to identify routinely obtainable pre- and intratherapeutic parameters to allow a prediction of overall survival in patients receiving Lu-177-PSMA-617 radioligand therapy. METHODS: Between January 2015 and December 2020 52 patients treated with a total of 146 cycles Lu-177-PSMA-617-RLT were retrospectively analysed in a single-center trial. The median overall survival time (OS) was compared to pre-therapeutic serological parameters, the extend of metastatic spread and previously performed therapies using Kaplan-Meier estimators and multivariate Cox-regression. Bonferroni-Holm correction was performed on all statistical tests. RESULTS: The median OS of all patients was 55.6 weeks. Multivariate Cox-regression revealed significant lower survival for decreased pretherapeutic hemoglobin levels (HR 0.698 per g/dl; 95%-CI 0.560-0.872; p = 0.001), increased lactate dehydrogenase (LDH) levels (HR 1.073 per 25 U/l; 95%-CI 1.024-1.125; p = 0.003) and the presence of hepatic metastasis (HR 6.981; 95%-CI 2.583-18.863; p < 0.001). Increased pretherapeutic c-reactive protein (CRP), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) levels were also associated with a shorter survival. A prostate-specific antigen decline after one therapy cycle did not significantly correlate with an increased survival. No significant relations were observed between overall survival time and other serological parameters or previously performed therapies. CONCLUSION: Pre-therapeutic hemoglobin and LDH levels, as well as the presence of hepatic metastasis are independent predictors of overall survival in patients receiving Lu-177-PSMA-617-RLT. CRP, ALP and GGT levels cloud be utilized as additional decision aids when a Lu-177-PSMA-617-RLT is intended. Trial Registration Not applicable (retrospective observational study).

Automated synthesis of [68Ga]Ga-FAPI-46 without pre-purification of the generator eluate on three common synthesis modules and two generator types.

BACKGROUND: The recent development of quinoline-based radiotracers, which act as fibroblast activation protein inhibitors (FAPIs), has shown promising preclinical and clinical advantages. [68Ga]Ga-FAPI-46 is a new radiotracer for in vivo detection of the fibroblast activation protein by positron emission tomography (PET). Recently, the automated synthesis of [68Ga]Ga-FAPI-46 was reported based on pre-concentration and purification of the generator eluate by using a cation exchange-cartridge. Our aim was to simplify the synthesis and shorten the automated synthesis of [68Ga]Ga-FAPI-46 to make it accessible and thus even more attractive to a broader clinical and scientific community. RESULTS: We developed and evaluated the GMP compliant automatic synthesis of [68Ga]Ga-FAPI-46 using two different 68Ge/68Ga generators (an Eckert & Ziegler, GalliaPharm generator, 1.85 GBq/50 mCi and an iThemba generator, 1.85 GBq/50 mCi) Somerset West, South Africa) and three different commercial and customized systems: the EasyOne module from Trasis; the GaSy module from Synthra with a customized synthesis template and a customized single use cassette. Additionally, the automatic synthesis of [68Ga]Ga-FAPI-46 was established on a GallElut synthesis module from Scintomics with fixed tubing. CONCLUSIONS: Independent of the synthesis modules or the generators employed we were able to complete the synthesis of [68Ga]Ga-FAPI-46 in 12 min including the process of purification and formulation. In all cases, the final products showed more than 99.5% chemical purity and the radiochemical yield reached around 92.5% (decay corrected). All quality control parameters (e.g. sterility, stability and radiochemical purity) were conform to the European Pharmacopoeia.

[Noninvasive functional lung imaging with hyperpolarized xenon : Breakthrough for diagnostics?] / Nichtinvasive funktionelle Lungenbildgebung mit hyperpolarisiertem Xenon : Durchbruch für die Diagnostik?

BACKGROUND: Magnetic resonance imaging (MRI) is a noninvasive technique that provides excellent contrast for soft tissue organs. However, due to the low density of protons and many air-tissue junctions, its application in the lung is limited. Thus, X­ray-based methods are often used here (with the well-known disadvantages of ionizing radiation). OBJECTIVES: In this review, we discuss pulmonary MRI with hyperpolarized xenon-129 (Xe-MRI). Xe-MRI provides unique valuable insights into lung microstructure and function, including gas exchange with red blood cells-parameters not accessible by any standard clinical methods. METHODS: By magnetic labelling, i.e. hyperpolarization, the signal from xenon-129 is amplified by up to 100,000 times. In this process, electrons from rubidium are first polarized to 100% using laser light and then transferred to xenon by collisions. Then the hyperpolarized gas is brought to the patient in a bag and inhaled shortly before the MRI scan. RESULTS: Using special programming (sequences) of the MRI, the ventilation, microstructure, or gas exchange of the lungs, can be displayed in 3D. This allows, for example, quantitative visualization of ventilation defects, alveolar size, tissue gas uptake and gas transfer to the blood. CONCLUSIONS: Xe-MRI provides unique information about the state of the lung-noninvasively, in vivo and in less than a minute.

A simple, reliable and accurate approach for assessing [131I]-capsule activity leading to significant reduction of radiation exposure of medical staff during radioiodine therapy.

PURPOSE: According to German law, the [131I]-capsule activity has to be checked in the context of radioiodine therapy (RIT) immediately before application. The measurement leads to significant radiation exposure of the medical personnel, especially of their hands. We aimed to establish a method for estimating [131I]-capsule activity by measuring the dose rate (DR) at contact of the delivered lead closed container carrying the [131I]-capsules and to evaluate radiation exposure in comparison to conventional [131I]-capsule measurement using a dose calibrator. METHODS: DR on the surface of the closed lead container was measured at two locations and correlated linearly with the [131I]-capsule activity measured in a dose calibrator to create calibrating curves. The hand and whole body (effective) doses were determined with official dose meters during validation of our method in clinical practice. RESULTS: The determination coefficients (R2) of linear calibration curves were greater than 0.9974. The total relative uncertainty for estimating [131I]-capsule activity with our method was <±7.5% which is lower than the uncertainty of the nominal activity and quite close to the threshold limit for the maximum allowed uncertainty of ± 5% for measuring activity in radioactive drugs. The reduction of the hand dose caused by our method was 97% compared with the conventional measurements of the [131I]-capsules in a dose calibrator. CONCLUSION: Measuring DR on the surface of the closed lead containers enables the [131I]-capsules activity to be estimated simply, reliably and with sufficient accuracy leading to significant reduction of the radiation exposure for the medical staff.

Photopharmacological Applications for Cherenkov Radiation Generated by Clinically Used Radionuclides.

Translational photopharmacological applications are limited through irradiation by light showing wavelengths within the bio-optical window. To achieve sufficient tissue penetration, using wavelengths >500 nm is mandatory. Nevertheless, the majority of photopharmacological compounds respond to irradiation with more energetic UV light, which shows only a minor depth of tissue penetration in the µm range. Thus, we became interested in UV light containing Cherenkov radiation (CR) induced as a by-product by clinically employed radionuclides labeling specific tissues. Therefore, CR may be applicable in novel photopharmacological approaches. To provide evidence for the hypothesis, we verified the clinically established radionuclides 68Ga and 90Y but not 18F in clinically used activities to be capable of generating CR in aqueous solutions. We then investigated whether the generated CR was able to photoactivate the caged kinase inhibitor cagedAZD5438 as a photoresponsive model system. Herein, 21% uncaging of the model system cagedAZD5438 occurred by incubation with 90Y, along with a non-specific compound decomposition for 68Ga and partly for 90Y. The findings suggest that the combination of a clinically employed radionuclide with an optimized photoresponsive agent could be beneficial for highly focused photopharmacological therapies.

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma.

Systemic radionuclide therapy with 177Lu-PSMA-617 is a novel treatment option in patients with metastasized and castration-resistant prostate cancer 4. The molecular target of the 177Lu-PSMA-617 radioligand therapy is the prostate-specific membrane antigen (PSMA) highly expressed on prostate cancer cells. Beyond the enhanced accumulation of PSMA on prostate cancer cells, PSMA expression is also found on the molecular surface or in the tumor-associated neovasculature of various tumor tissues including sarcomas of the soft tissue 2. Thus, PSMA has theoretically been discussed as a possible future target for systemic radioligand therapy with 177Lu-PSMA-617 even in non-prostate malignancies 1.Here we report on a female patient with extended metastasized leiomyosarcoma experimentally treated with one application of 177Lu-PSMA-617 radioligand therapy.

Vedolizumab is associated with changes in innate rather than adaptive immunity in patients with inflammatory bowel disease.

OBJECTIVE: Vedolizumab, a monoclonal antibody directed against the integrin heterodimer α4ß7, is approved for the treatment of Crohn's disease and ulcerative colitis. The efficacy of vedolizumab has been suggested to result from inhibition of intestinal T cell trafficking although human data to support this conclusion are scarce. We therefore performed a comprehensive analysis of vedolizumab-induced alterations in mucosal and systemic immunity in patients with inflammatory bowel disease (IBD), using anti-inflammatory therapy with the TNFα antibody infliximab as control. DESIGN: Immunophenotyping, immunohistochemistry, T cell receptor profiling and RNA sequencing were performed using blood and colonic biopsies from patients with IBD before and during treatment with vedolizumab (n=18) or, as control, the anti-TNFα antibody infliximab (n=20). Leucocyte trafficking in vivo was assessed using single photon emission computed tomography and endomicroscopy. RESULTS: Vedolizumab was not associated with alterations in the abundance or phenotype of lamina propria T cells and did not affect the mucosal T cell repertoire or leucocyte trafficking in vivo. Surprisingly, however, α4ß7 antibody treatment was associated with substantial effects on innate immunity including changes in macrophage populations and pronounced alterations in the expression of molecules involved in microbial sensing, chemoattraction and regulation of the innate effector response. These effects were specific to vedolizumab, not observed in response to the TNFα antibody infliximab, and associated with inhibition of intestinal inflammation. CONCLUSION: Our findings suggest that modulation of innate immunity contributes to the therapeutic efficacy of vedolizumab in IBD. TRIAL REGISTRATION NUMBER: NCT02694588.

Evaluation of the diagnostic value of preoperative sentinel lymph node (SLN) imaging in penile carcinoma patients without palpable inguinal lymph nodes via single photon emission computed tomography/computed tomography (SPECT/CT) as compared to planar scintigraphy.

BACKGROUND: Sentinel lymph node (SLN) biopsy represents a well-established diagnostic tool for the assessment of lymphatic metastasis. Correct pre- and intraoperative visualization of SLN is of the utmost importance to ensure the safety and feasibility of the procedure. Aim of this study was to evaluate the diagnostic value of preoperative SLN imaging via single photon emission computed tomography/computed tomography (SPECT/CT) and planar scintigraphy in patients with penile carcinoma with nonpalpable inguinal lymph nodes. MATERIALS AND METHODS: After peritumoral intradermal tracer injection (150MBq/4.05mCi Tc-99m nanocolloid), we acquired planar scintigraphies including indirect body contouring using a twin head gamma camera. Subsequently we acquired SPECT/CT images of the abdomen via a hybrid system. Prospective evaluation of 52 groins in 26 examined patients was done for all image files obtained with both techniques by 2 trained experts in consensual assessment. RESULTS: A total of 71 SLNs in 37 groins were identified by means of planar scintigraphy. In these images, no radiolabeled lymph nodes were visualized in 15 out of 52 groins (28.8%). The SPECT/CT images showed a total of 82 SLNs in 42 groins. In 19.2% (10 of the 52 groins), there was no visualization of lymph nodes in SPECT/CT. 8 SLNs in 7 groins that were visualized in the planar technique were found to be false positive by SPECT/CT. In total, 19 SLNs in 16 groins that were overlooked by planar imaging could only be detected by SPECT/CT. In contrast to planar scintigraphy, SPECT/CT imaging enabled clear and precise anatomical localization of SLNs in all 42 groins where radiolabeled SLNs were visible. Even under consideration of all lymphatic drainage regions, statistical evaluation showed a significantly higher number of detected SLNs with SPECT/CT in comparison to the planar technique (P = 0.0022). CONCLUSION: In these patients SPECT/CT is capable of visualizing SLNs that cannot be detected with planar imaging. The SPECT/CT technique reduces the number of false positive findings from planar SLN imaging and is able to show anatomic SLN localization more precisely. If possible, preoperative SLN imaging should be performed by means of the SPECT/CT technique in patients with this tumor entity.

Pioglitazone induces cell growth arrest and activates mitochondrial apoptosis in human uterine leiomyosarcoma cells by a peroxisome proliferator-activated receptor γ-independent mechanism.

The peroxisome proliferator-activated receptor γ (PPARγ) agonists, thiazolidinediones, including pioglitazone (PIO) exhibit anti-tumour activities in cancer cells. The present study investigates the effects of PIO on cell proliferation and apoptosis in SK-UT-1 cells, a human uterine leiomyosarcoma cell line, and human uterine smooth muscle cells (HUtSMC). The proliferation and viability of SK-UT-1 cells treated with vehicle or PIO were assessed by cell counting and WST-1 assay. The activity of MEK/ERK and p38 MAPK signalling pathways and the expression of p53, the cyclin-dependent kinase inhibitor, p21, Bax, Bad and Bim proteins and cleaved caspase-3 were analysed by Western blotting. Quiescent SK-UT-1 cells intensively proliferate and display high levels of phosphorylated, activated MEK1/2, ERK1/2 and p38 MAPK. PIO (10 or 25 µM) induced time- and dose-dependently cell-growth arrest, reduced the cell numbers and effectively suppressed the over-activated MEK/ERK and p38 MAPK signalling pathways as evidenced by the abolished levels of phosphorylated MEK1/2, ERK1/2 and p38 MAPK. PIO activated the intrinsic apoptotic pathway, i.e. up-regulated the p53, p21, Bax and Bad proteins and cleaved caspase-3. PIO also reduced cell numbers of highly proliferative SK-UT-1 cells cultured in growth medium. The anti-proliferative and pro-apoptotic actions of PIO were not PPARγ dependent and exclusive for SK-UT-1 cells as PIO did not interfere with the proliferation of HUtSMC. The pronounced anti-tumorigenic effects of PIO in SK-UT-1 cells address an important issue about the relevance of the PPARγ agonist in the treatment of the human uterine leiomyosarcoma.

Pharmacologically Inactive Bisphosphonates as an Alternative Strategy for Targeting Osteoclasts: In Vivo Assessment of 5-Fluorodeoxyuridine-Alendronate in a Preclinical Model of Breast Cancer Bone Metastases.

Bisphosphonates have effects that are antiresorptive, antitumor, and antiapoptotic to osteoblasts and osteocytes, but an effective means of eliciting these multiple activities in the treatment of bone metastases has not been identified. Antimetabolite-bisphosphonate conjugates have potential for improved performance as a class of bone-specific antineoplastic drugs. The primary objective of the study was to determine whether an antimetabolite-bisphosphonate conjugate will preserve bone formation concomitant with antiresorptive and antitumor activity. 5-FdU-ale, a highly stable conjugate between the antimetabolite 5-fluoro-2'-deoxyuridine and the bisphosphonate alendronate, was tested for its therapeutic efficacy in a mouse model of MDA-MB231 breast cancer bone metastases. In vitro testing revealed osteoclasts to be highly sensitive to 5-FdU-ale. In contrast, osteoblasts had significantly reduced sensitivity. Tumor cells were resistant in vitro but in vivo tumor burden was nevertheless significantly reduced compared with untreated mice. Sensitivity to 5-FdU-ale was not mediated through inhibition of farnesyl diphosphate synthase activity, but cell cycle arrest was observed. Although serum tartrate-resistant acid phosphatase (TRAP) levels were greatly reduced by both drugs, there was no significant decrease in the serum bone formation marker osteocalcin with 5-FdU-ale treatment. In contrast, there was more than a fivefold decrease in serum osteocalcin levels with alendronate treatment (p < 0.001). This finding is supported by time-lapse micro-computed tomography analyses, which revealed bone formation volume to be on average 1.6-fold higher with 5-FdU-ale treatment compared with alendronate (p < 0.001). We conclude that 5-FdU-ale, which is a poor prenylation inhibitor but maintains potent antiresorptive activity, does not reduce bone formation and has cytostatic antitumor efficacy. These results document that conjugation of an antimetabolite with bisphosphonates offers flexibility in creating potent bone-targeting drugs with cytostatic, bone protection properties that show limited nephrotoxicity. This unique class of drugs may offer distinct advantages in the setting of targeted adjuvant therapy and chemoprevention of bone diseases. © 2016 American Society for Bone and Mineral Research.

A study on the value of computer-assisted assessment for SPECT/CT-scans in sentinel lymph node diagnostics of penile cancer as well as clinical reliability and morbidity of this procedure.

BACKGROUND: Because of the increasing importance of computer-assisted post processing of image data in modern medical diagnostic we studied the value of an algorithm for assessment of single photon emission computed tomography/computed tomography (SPECT/CT)-data, which has been used for the first time for lymph node staging in penile cancer with non-palpable inguinal lymph nodes. In the guidelines of the relevant international expert societies, sentinel lymph node-biopsy (SLNB) is recommended as a diagnostic method of choice. The aim of this study is to evaluate the value of the afore-mentioned algorithm and in the clinical context the reliability and the associated morbidity of this procedure. METHODS: Between 2008 and 2015, 25 patients with invasive penile cancer and inconspicuous inguinal lymph node status underwent SLNB after application of the radiotracer Tc-99m labelled nanocolloid. We recorded in a prospective approach the reliability and the complication rate of the procedure. In addition, we evaluated the results of an algorithm for SPECT/CT-data assessment of these patients. RESULTS: SLNB was carried out in 44 groins of 25 patients. In three patients, inguinal lymph node metastases were detected via SLNB. In one patient, bilateral lymph node recurrence of the groins occurred after negative SLNB. There was a false-negative rate of 4 % in relation to the number of patients (1/25), resp. 4.5 % in relation to the number of groins (2/44). Morbidity was 4 % in relation to the number of patients (1/25), resp. 2.3 % in relation to the number of groins (1/44). The results of computer-assisted assessment of SPECT/CT data for sentinel lymph node (SLN)-diagnostics demonstrated high sensitivity of 88.8 % and specificity of 86.7 %. CONCLUSIONS: SLNB is a very reliable method, associated with low morbidity. Computer-assisted assessment of SPECT/CT data of the SLN-diagnostics shows high sensitivity and specificity. While it cannot replace the assessment by medical experts, it can still provide substantial supplement and assistance.

10-Year experience regarding the reliability and morbidity of radio guided lymph node biopsy in penile cancer patients and the associated radiation exposure of medical staff in this procedure.

BACKGROUND: The guidelines of the European Association of Urologists (EAU), of the German Society of Nuclear Medicine (DGN), and the European Society for Medical Oncology (ESMO) recommend sentinel lymph node biopsy (SLNB) for lymph node staging in penile cancer with non-palpable inguinal lymph nodes as one diagnostic method. Despite this, the method is neither widely nor regularly applied in Germany - the same applies to many other countries, which may be due to insecurity in dealing with open radioactive tracers. This study aims to assess the reliability and morbidity of this method, as well as the associated radioactive burden for clinical staff. METHODS: Between 2006 and 2016, 34 patients with an invasive penile carcinoma and inconspicuous inguinal lymph node status underwent SLNB in 57 groins after application of a radiotracer (Tc-99 m nanocolloid). We collected the results prospectively. The reliability of the method was assessed by determining the false-negative rate. In addition, we evaluated complication rates and determined the radioactive burden for the clinical staff both pre- and intraoperatively. RESULTS: SLNB was performed in 34 patients with penile cancer with non-palpable inguinal lymph nodes in 57 groins. In two patients inguinal lymph node metastases were detected by means of SLNB. In one patient recurrent inguinal lymph node disease was found after negative SLNB in both groins. Thus, the false negative rate was 3.13 % per patient (1/32 patients) and 3.51 % per groin (2/57 groins). The morbidity rate was 2.94 % per patient (1/34 patients) and 1.75 % per groin (1/57 groins). Radiation exposure for the clinical staff during this procedure was low at a maximum of ca. four µSV per intervention. CONCLUSIONS: SLNB is a reliable method with low morbidity that is associated with a low radiation burden for clinical staff. Due to the enhanced methodological and logistic demands, this intervention should be performed in specialized centres and in an interdisciplinary approach.

Value and efficiency of sentinel lymph node diagnostics in patients with penile carcinoma with palpable inguinal lymph nodes as a new multimodal, minimally invasive approach.

PURPOSE: The international guidelines recommend sentinel lymph node biopsy (SLNB) for lymph node staging in penile cancer with non-palpable inguinal lymph nodes (LN) but it is not recommended with palpable inguinal LN. The aim of this study was to evaluate the reliability and morbidity of SLNB in combination with an ultrasound-guided resection of suspect inguinal LNs as a new multimodal, minimally invasive staging approach in these patients. METHODS: We performed SLNB in 26 penile cancer patients with 42 palpable inguinal LNs. Prior to the combined staging procedures the patients underwent an ultrasound examination of the groins as well as planar lymphatic drainage scintigraphy and SPECT/CT scans. During the surgical procedure, the radioactive-labelled sentinel lymph nodes and, in addition, sonographically suspect LNs, were resected under ultrasound guidance. Follow-up screening was done by ultrasound examination of the groins according to the guidelines of the European Association of Urology. RESULTS: Nineteen groins of 42 preoperatively palpable inguinal findings were histologically tumor-positive. SLNB alone showed lymphogenic metastases in 14 groins. Sonography revealed five further metastatic groins, which would not have been detected during SLNB due to a tumor-related blockage of lymphatic drainage or a so-called re-routing of the tracer. During follow-up, none of the 28 groins with tumor-negative LN status showed any LN recurrence in this combined investigation technique. The median follow-up period was 46 (24 to 92) months. Morbidity of this procedure was low at 4.76 % in relation to the number of groins resp. 7.69 % in relation to the number of patients. CONCLUSIONS: The results show that this combined procedure is a reliable multimodal diagnostic approach for treatment of penile cancer patients with palpable inguinal LNs. It is associated with low morbidity rates. SLNB alone would lead to a significantly higher false-negative rate in these patients. The encouraging results of this work can extend the range of indications for nuclear medicine in the form of SLNB using radioactive tracers in this patient group.

Effective method of measuring the radioactivity of [ 131I]-capsule prior to radioiodine therapy with significant reduction of the radiation exposure to the medical staff.

Radiation Protection in Radiology, Nuclear Medicine and Radio Oncology is of the utmost importance. Radioiodine therapy is a frequently used and effective method for the treatment of thyroid disease. Prior to each therapy the radioactivity of the [131I]-capsule must be determined to prevent misadministration. This leads to a significant radiation exposure to the staff. We describe an alternative method, allowing a considerable reduction of the radiation exposure. Two [131I]-capsules (A01 = 2818.5; A02 = 7355.0 MBq) were measured multiple times in their own delivery lead containers - that is to say, [131I]-capsules remain inside the containers during the measurements (shielded measurement) using a dose calibrator and a well-type and a thyroid uptake probe. The results of the shielded measurements were correlated linearly with the [131I]-capsules radioactivity to create calibration curves for the used devices. Additional radioactivity measurements of 50 [131I]-capsules of different radioactivities were done to validate the shielded measuring method. The personal skin dose rate (HP(0.07)) was determined using calibrated thermo luminescent dosimeters. The determination coefficients for the calibration curves were R2 > 0.9980 for all devices. The relative uncertainty of the shielded measurement was < 6.8%. At a distance of 10 cm from the unshielded capsule the HP(0.07) was 46.18 µSv/(GBq•s), and on the surface of the lead container containing the [131I]-capsule the HP(0.07) was 2.99 and 0.27 µSv/(GBq•s) for the two used container sizes. The calculated reduction of the effective dose by using the shielded measuring method was, depending on the used container size, 74.0% and 97.4%, compared to the measurement of the unshielded [131I]-capsule using a dose calibrator. The measured reduction of the effective radiation dose in the practice was 56.6% and 94.9 for size I and size II containers. The shielded [131I]-capsule measurement reduces the radiation exposure to the staff significantly and offers the same accuracy of the unshielded measurement in the same amount of time. In order to maintain the consistency of the measuring method, monthly tests have to be done by measuring a [131I]-capsule with known radioactivity.

Value and Efficacy of Sentinel Lymph Node Diagnostics in Patients With Penile Carcinoma With Nonpalpable Inguinal Lymph Nodes: Five-Year Follow-up.

PURPOSE: Sentinel lymph node biopsy (SLNB) has been described as a minimally invasive method for lymph node staging in patients with a penile carcinoma and nonpalpable inguinal nodes in national and international guidelines of involved professional societies. However, this method is rarely used. The aim of this study was to validate reliability and morbidity of this method and to discuss radiation exposure of persons involved. METHODS: Twenty-eight patients with histologically negative sentinel lymph nodes in 47 groins with nonpalpable inguinal lymph nodes were included in this study (17 T1(a/b)-, 8 T2- and 3 T3-stages). We recorded prospectively all cases of lymph node recurrence and complications in patients with initially nonpalpable inguinal lymph nodes and histologically negative sentinel lymph nodes. False-negative findings and morbidity were calculated as qualitative criteria. Inguinal regions with palpable lymph nodes and/or evidence of metastases were not considered in accordance with the guidelines. RESULTS: During a median follow-up of 68 (4-131) months, we observed one case of bilateral lymph node recurrence and one case of prolonged inguinal lymphorrhea, which could be managed conservatively. Per inguinal region, false-negative rate was 4.25%, and morbidity rate was 2.12%; seen per patient, the rates were both 3.57%. CONCLUSIONS: Sentinel lymph node biopsy under use of radioactive tracers is a reliable method of lymph node staging in patients with penile carcinoma and nonpalpable inguinal lymph nodes. The methodical complexity is justified by high reliability and low radiation exposure for both patient and medical staff and low morbidity rates.