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Zusammenfassung Hintergrund Eine Blockade von Immun-Escape-Mechanismen (z. B. PD1 /PD-L1) mit Immun-Checkpoint-Inhibition (ICI) kann das Überleben von Patienten mit fortgeschrittenem NSCLC wesentlich verlängern und ausgeprägte Remissionen induzieren. Eine neoadjuvante ICI bei Patienten mit resektablem (UICC-Stadium III) oder oligometastasiertem (UICC-Stadium IVA) NSCLC wurde bisher kaum untersucht. Patienten/Methoden Es wurden Biopsien von Patienten mit lokal fortgeschrittenem oder oligometastasiertem NSCLC untersucht. Es erfolgte bei einer PD-L1-Expression > 50 %, gutem ECOG-Status und zu erwartender Operabilität die ICI-Applikation und nach ca. 4 Wochen die thoraxchirurgische OP. Alle Patienten erhielten ein komplettes Staging einschließlich PET-CT, cMRT und endobronchialem Ultraschall. Es wurden die Verträglichkeit, das radiologische und histologische Tumoransprechen und das chirurgische Outcome analysiert. Ergebnisse 4 Patienten (2 männlich, 2 weiblich, Alter 56 – 78 Jahre, n = 3 Adenokarzinom, n = 1 Plattenepithelkarzinom) erhielten präoperativ einen ICI. Alle Patienten hatten lokal fortgeschrittene Tumore, und die mediastinalen Lymphknoten waren in 3 Fällen positiv. Bei einem Patienten lag eine isolierte Hirnmetastase vor, welche stereotaktisch radiotherapiert wurde. Alle Patienten erhielten präoperativ komplikationslos 2 – 6 Zyklen eines ICI (3 × Pembrolizumab; 1 × Atezolizumab). Dies führte nicht zu einer Verzögerung der OP. Nach iRECIST zeigten 3 Tumore eine partielle response (PR), und ein Patient wies ein stable disease (SD) auf. Alle Tumore wurden komplett reseziert, und die OP erwies sich trotz inflammatorischer Veränderungen als technisch unproblematisch. Es gab keine behandlungsbezogene Morbidität oder Mortalität und keine perioperativen Komplikationen. In den Resektaten waren jeweils 2-mal ein komplettes pathologisches Ansprechen (CPR), Regressionsgrad III nach Junker, und 2-mal ein Regressionsgrad IIa nach Junker nachweisbar. Das mittlere Follow-up betrug 12 (1 – 24) Monate. Die PPR-Patienten entwickelten entweder Fernmetastasen nach 6 Monaten oder ein Lokalrezidiv nach 4 Monaten. Die CPR-Patienten sind bisher rezidivfrei. Schlussfolgerungen Eine neoadjuvante Therapie mit ICI ist gut verträglich und kann bei ausgewählten Patienten eine komplette Tumorremission induzieren. Die Behandlung hat keinen negativen Einfluss auf den chirurgischen Eingriff. Die Prognose ist vielversprechend bei CPR und eingeschränkt bei PPR.

ZusammenfassungFür das fortgeschrittene Radiojod-refraktäre differenzierte Schilddrüsenkarzinom (DTC) als auch für das progrediente medulläre Schilddrüsenkarzinom sind seit mehreren Jahren Tyrosinkinase-Inhibitoren (TKI) als wirksame Therapieoptionen zugelassen. Nicht zuletzt aufgrund des Toxizitätsprofiles der TKIs erfolgt deren Einsatz individualisiert und risikoadaptiert nach Ausschöpfen lokaler palliativer Therapieverfahren und wenn bei großer Tumormasse und/oder signifikantem Fortschreiten ein weiteres Abwarten nicht mehr vertretbar erscheint. Für das DTC gibt es zwei zugelassene Tyrosinkinaseinhibitoren, Lenvatinib und Sorafenib; für das MTC sind es ebenfalls zwei, Vandetanib und Cabozantinib. Hinzu kommen, vor allem in letzter Zeit, (relativ) selektive Inhibitoren einzelner Tyrosinkinasen (z. B. BRAF, MEK, NTRK, RET und mTOR), die im Rahmen von Studien oder im individuellen Heilversuch zur Verfügung stehen. Kürzlich erlangten zwei NTRK-Inhibitoren die europäische Zulassung und können bei Vorliegen einer NTRK-Fusion eingesetzt werden; leider ist diese Fusion jedoch relativ selten beim Schilddrüsenkarzinom zu finden.In Summe sind die Nebenwirkungen der selektiven Inhibitoren meist geringer als die der bisher zugelassenen Medikamente, bei teils besserer, teils gleicher und teils etwas schlechterer Wirkung. Es steht zu erwarten, dass die selektiven Inhibitoren zukünftig das therapeutische Spektrum ergänzen werden. Grundvoraussetzung ist jedoch eine molekulare Analyse von Tumorgewebe mit Nachweis einer spezifischen Veränderung im Sinne eines „drugable target“. Um eine optimale individuelle Therapieplanung unter Berücksichtigung aller möglichen Therapieoptionen, inklusive Einschluss in klinische Studien, zu gewährleisten, sollten Patienten mit fortgeschrittenem MTC oder Radiojod-refraktären DTC interdisziplinär an spezialisierten Zentren (mit-)betreut werden.

ZusammenfassungIn der Nebenniere liegen 2 distinkt unterschiedliche Gewebe, das Nebennierenmark und die Nebennierenrinde vor. Beide Gewebearten sezernieren unterschiedliche Hormone und besitzen eigene molekulare Charakteristika, die für eine spezifische Bildgebung mit Radiotracern genutzt werden können. Für das Nebennierenmark sind dies der Noradrenalin-Re-Uptake-Transporter und, beschränkt, auch der Somatostatinrezeptor. Für die Nebennierenrinde ist eine spezifische Darstellung von Enzymen der Cortisol- und Aldosteronbiosynthese möglich. In theranostischen Ansätzen wurden alle Zielstrukturen bisher bereits für gezielte Radionuklidtherapien genutzt, jedoch ist bisher lediglich die Noradrenalin-Re-Uptake-Transporter-gezielte 131I-metaIodBenzylGuanidin (mIBG)-Behandlung klinisch etabliert.

ZusammenfassungFür die Berechnung der Therapieaktivität im Rahmen der Selektiven Internen Radiotherapie (SIRT oder auch Radioembolisation) existieren unterschiedlich elaborierte Berechnungsmodelle. Diese besitzen empirischen Charakter bzw. basieren auf makroskopischen Ansätzen unter der Annahme einer Gleichverteilung der Mikrosphären und damit der akkumulierten Dosis (MIRD-basierter Modellansatz). Eine Inhomogenität in der Anreicherung des Radioembolisats, welche regulär durch die post-therapeutische Bildgebung beobachtet wird, findet in den Dosierungskonzepten keine Berücksichtigung. Für die weitere Entwicklung wäre es hier wünschenswert, radiobiologische Konzepte stärker zu integrieren und eine Dosierung der Therapieaktivität unter Berücksichtigung der (limitierenden) gewebsspezifischen Toleranzen durchzuführen.Generell sind die Bewertung der Effektivität und der Nebenwirkungen sowie die damit verbundene Definition von Toleranzdosen/Zieldosen schwierig. Die verfügbaren Daten weisen aufgrund der Heterogenität der untersuchten Endpunkte, unterschiedlicher basaler Leberfunktion und individueller Erkrankungshistorien (Vortherapie) eine große Streuung und eine damit verbundene große Unsicherheit auf.

In patients with resistant hypertension and large blood pressure fluctuations, the role of orthostatic hypertension, associated with position-dependent renal perfusion disturbances, has not been investigated in detail yet. In this regard, four patients from our outpatient clinic were investigated by the use of 24-h ambulatory blood pressure monitoring (ABPM), active standing test, renal duplex sonography and Tc99m-mercaptoacetyltriglycine [MAG3] renal scintigraphy in supine and upright position. Four patients (three males and one female; 51–79 years) with a mean of 4.25 antihypertensive drugs including a diuretic were evaluated. The recorded blood pressure fluctuations were up to 89/58–198/121 mmHg. Three patients exhibited an extreme and one a normal dipping pattern in the 24-h ABPM. Three patients demonstrated a hypertensive orthostatic reaction in the active standing test. By duplex sonography, a bilateral decrease in the overall intrarenal resistive indices was shown in two patients, a unilateral overall decrease in one patient and a localized decrease in the last patient. From a morphological standpoint of view, all patients had a normal anatomical position and a physiologic descent of both kidneys. But the normalized tubular extraction rate was pathologic in all patients in the upright body position and normalized when lying down in three patients. Position-dependent renal perfusion should be considered in patients with large blood pressure fluctuations and extreme dipping. If morphological imaging shows no abnormalities, functional imaging provides additional information. Further investigation is needed, foremost if nephropexy could improve blood pressure control in some of these patients.

The aim of the study was to establish the setup and workflow for delivering focal MRI-guided high-dose-rate (HDR) brachytherapy for prostate cancer (PCA) and to assess patient comfort and safety aspects of MRI-guided single-fraction HDR. Patients with histologically proven focal low- to intermediate-risk PCA with a single PIRADS 4/5 lesion were treated with percutaneous interstitial HDR brachytherapy in a single fraction with a minimum dose for the gross tumor volume of 20 Gy while sparing the organ at risk (OAR). Using a 3T-MRI, brachytherapy catheters were placed transgluteal in freehand technique. No antibiotic therapy or general analgesics were administered. Patient data, procedure time, patient discomfort, and complications were recorded. Quarterly PSA controls, biannual follow-up imaging, and annual re-biopsy were planned. So far, 9 patients were successfully treated and followed for 6 months. Mean intervention time was 34 min. Using the VAS scale, the pain reported for the intervention ranged from 2 to 3. Short-term follow-up showed no acute genitourinary or gastrointestinal toxicity so far. None of the patients displayed signs of infection. PSA levels in all patients decreased significantly. On follow up no residual PCA was detected treated region so far. PSA levels in all patients decreased significantly. On follow-up, no residual PCA was detected so far. MR-guided single-fraction focal HDR brachytherapy for localized PCA is feasible as well as safe for the individual patient. Catheters can be placed accurately and maximum therapeutic dose distribution can be restricted to the tumor. Countersigning the minimally invasive character of the procedure, no general anesthesia or antibiosis is necessary. • MR-guided focal HDR brachytherapy allows an accurate placement of catheters with maximum therapeutic dose distribution restricted to the tumor. • No major anesthesia or antibiosis is necessary emphasizing the minimal invasive character of the procedure. • Patients with low- and intermediate-risk prostate carcinoma in particular may benefit to halt disease progression whereas treatment-related morbidity is reduced compared with radical therapy.

Summary Aim: After detection of obstructive uropathy (OU), the indication for or against surgery is primarily based on the differential renal function (DRF). This is to compare functional magnetic resonance urography (fMRU) with dynamic renal scintigraphy (DRS) to assess OU and DRF in infants and children. Patients, methods: Retrospective analysis in 30 patients (female: 16; male: 14; median age: 5.5 years [0.2-16.5]), divided into subgroup A (age: 0-2 years; n = 16) and B (> 2-17 years; n = 14). fMRU was assessed by measuring renal transit time (RTT) and volumetric DRF with CHOP fMRU tool (CT) and ImageJ MRU plug-in (IJ). OU detection by fMRU was compared with DRS (standard of reference) using areas under the curves (AUC) in ROC analyses. Concordant DRF was assumed if absolute deviation between fMRU and DRS was < 5 %. Results: DRS confirmed fixed OU in 4/31 kidneys (12.9 %) in subgroup A. AUC of CT was 0.94 compared with 0.93 by IJ. Subgroup B showed fixed OU in 1/21 kidneys (4.8 %) with AUCs of 0.98 each. RTT measured neither by CT nor by IJ in confirmed fixed OU was < 1200 s – resulting in negative predictive values of 1.0 each. In subgroup A, DRF was concordant in 81.3 % of the kidneys for CT and DRS compared with 75.0 % for IJ and DRS. In subgroup B, CT and DRS were concordant in 91.7 %, and IJ and DRS in 45.8 % of the kidneys. Conclusion: fMRU accurately excluded fixed OU in infants and children, independent from the software used for quantification. However, assessment of DRF with fMRU deviated from DRS especially in infants who may profit most from early intervention. Thus, fMRU cannot fully replace DRS as primary functional examination. If, for clinical reasons, fMRU is performed in first place and it cannot exclude fixed OU, it should be followed by DRS for validation and DRF quantification.

Summary Aim: 223Radium-dichloride (223Ra) administration is an upcoming therapeutic option in patients with castration-resistant metastatic prostate cancer (mCRPC), whose renal and faecal excretion of 223Ra has been primarily estimated from data of a phase-I clinical trial in patients with normal renal function. In the rare case of concomitant renal insufficiency requiring haemodialysis (HD), an estimation of the contamination of dialysate would be beneficial. Methods: The excretion of 223Ra and its concentration in the dialysate in a patient with mCRPC and end-stage renal disease was examined for six consecutive treatment cycles. Dialysate samples were measured using a commercial system with NaI-scintillation detector. Results: HD showed a residual activity level in the remaining dialysate. The excreted activity was a median of 46.1 kBq (range = 42.0 83.4 kBq) and 11.2 kBq (range = 8.419.9 kBq) for the first (24 h post injection p.i.) and second HD (96 h p.i.), respectively. The activity concentration decreased significantly from a median of 4.18 kBq/l (range = 2.98-5.14 kBq/l) to 0.85 kBq/l (range=0.69-1.31 kBq/l, p < 0.0001). For all consecutive time points, the activity concentration further decreased significantly (p < 0.0001). The activity concentration of dialysate from HD performed 125.4 h p.i. [95 % confidence interval = 120.5-130.4 h p.i.] reached the threshold for unrestricted waste disposal. Conclusion: The observed extraction of 223Ra by HD exceeded the data determined from the phase-I study. The activity concentration in the dialysate observed for the first HD’s p.i. was above the threshold for unrestricted disposal of radioactive waste in Germany. Therefore, the specific requirement for waste handling has to be followed to fulfil the radiation protection regulations.

For lung cancer staging, the involvement of lymph nodes in the mediastinum, meaning along the trachea and bronchi, has to be assessed. Depending on the staging results, treatment options include radiation therapy, chemotherapy, or lymph node resection. We present a processing pipeline to automatically generate visualization-supported case reports to simplify reporting and to improve interdisciplinary communication, e. g. between nuclear medicine physicians, radiologists, radiation oncologists, and thoracic surgeons. To evaluate our method, we obtained detailed feedback from the local division of nuclear medicine: Although patient-specific anatomy was not yet considered, the presented approach was deemed to be highly useful from a clinical perspective.

Rationale Pre-operative lobar function is estimated by scintigraphy in patients with pulmonary malignancies and compromised function. This study compared the lobar perfusion determined by scintigraphy (PS) with data from SPECT/low-dose-CT (SPECT/ldCT) analyzed manually and semi-automatic. Methods Retrospective analysis on 39 patients (m/f = 25/14; age: 72.5 [22–89] years) with indication for pulmonary perfusion scintigraphy. Imaging was performed using SPECT/ldCT. Data was analyzed manually and by semi-automatic software. Readers’ confidence in 3D-segmentation was scored by two independent readers. Interrater agreement was calculated. In addition, Spearman’s rank correlation and Wilcoxon’s test were used. Results Results from PS differed significantly from SPECT/ldCT processed manually or semi-automatically in 4/5 lobes (total difference ≤21.6%; rho ≥0.44) and in 3/5 (total difference 21.6%; rho ≥0.37), respectively. Readers’ confidence in 3D-segmentation showed a perfect interrater agreement (κ = 0.98). Conclusion Quantification of lobar perfusion by SPECT/ldCT differs significantly from planar scintigraphy (e.g., with potential influence on therapy). The semi-automatic software analysis provides an applicable methodology.

Knocheneigene maligne Tumoren, Tumoren mit sekundarer Knochenbeteiligung sowie benigne Knochenerkrankungen im Kindes- und Jugendalter stellen den behandelnden Arzt oftmals vor grose Herausforderungen hinsichtlich des weiteren Vorgehens. Dieser Artikel adressiert die Knochenszintigrafie als integralen Bestandteil der Diagnostik o.g. Erkrankungen. Neben Indikationen werden altersspezifisch vorbereitende Masnahmen und angepasste Untersuchungsdurchfuhrungen, Befundinterpretation sowie die Strahlenexposition dargestellt. Hierbei wird sowohl auf die planare Szintigrafie als auch auf raumlich aufgeloste Verfahren wie die SPECT bzw. SPECT/CT eingegangen.

Perfusion scintigraphy using 99mTc-labeled albumin aggregates is mandatory before hepatic radioembolization with 90Y-microspheres. As part of a prospective trial, the intrahepatic and intrapulmonary stability of 2 albumin compounds, 99mTc-MAA (macroaggregated serum albumin [MAA]) and 99mTc-HSA (human serum albumin [HSA]), was assessed. Methods: In 24 patients with metastatic colorectal cancer, biodistribution (liver, lung) and liver–lung shunt (LLS) of both tracers (12 patients each) were assessed by sequential planar scintigraphy (1, 5, and 24 h after injection). Results: Liver uptake of both albumin compounds decreased differently. Although initial LLSs at 1 h after injection were similar in both groups, MAA-LLS increased significantly from 1 (3.9%) to 5 h (7.7%) and 24 h (9.9%) after injection, respectively. HSA-LLS did not change significantly (1 to 5 h), indicating a steady state of pulmonary and intrahepatic degradation. Conclusion: Compared with 99mTc-MAA-microspheres, 99mTc-HSA-microspheres are likely more resistant to degradation over time, allowing a reliable LLS determination even at later time points.

Magnetic resonance urography (MRU) provides high resolution imaging of the urogenital system and the use of paramagnetic contrast agents enables a functional depiction. This review summarizes existing data concerning this diagnostic procedure in pediatric urology. A systematic search and assessment of the literature was performed.A total of 12 studies were reviewed in detail. In mostly small study populations a great heterogeneity concerning methodology, use of comparative examinations and standards of reference was noted. Besides the quality of anatomical imaging, the functional study of renal excretory function and differential renal function was also assessed. Only a few studies performed statistical analyses.The authors' rating of MRU was mostly positive. Due to methodical weaknesses, lack of independent standards of reference and statistical analyses the overall level of evidence was low. Further high quality studies will be necessary to assess the value of MRU for the diagnostic workup in pediatric urology.

Routine visual assessment of positron emission tomography (PET) for thoracic lymph node (LN) staging in patients with non-small cell lung cancer (NSCLC) is limited by a lack of reliable assessment criteria. This study evaluates the accuracy and inter-rater agreement of a standardized approach with unified windowing and a PET-based visual score.This retrospective analysis included pretherapeutic FDG-PET data of 86 patients with NSCLC. After standardized windowing (threshold: 2×liver SUVmean) the LN uptake was assessed visually by three independent readers with varying levels of experience using a 4-step score (1, LN uptake≤mediastinal blood pool structures (MBPS); 2, MBPSLNliver; 3, liver≤LN'black'; 4, LN appears 'black'). ROC analyses and respective areas under the curve (AUC) based on histology/cytology as standard of reference. Agreement was analyzed with Cohen's kappa (κ, pairwise) and Fleiss' κ (overall). Subgroup analyses separated between hilar vs. mediastinal LNs, adenocarcinoma vs. squamous cell carcinoma and grading G1/2 vs. G3/4.Fifty-four of the 278LNs (19.4%) were malignant (optimal cut-off to differentiate benign vs. malignant, score3). The inexperienced (n=1), advanced (n=1), and expert readers (n=1) achieved similar accuracies of 93.5%, 91.4% and 92.1%, respectively (P0.05 each). Cohen's κ ranged from 0.92 to 0.96 and Fleiss' κ was 0.93. ROC-analyses showed no significant differences between attendant readers within any subgroup (AUC, 0.92-0.96).Applying unified windowing, the introduced PET-score achieved highly accurate and robust LN assessment. This approach may shorten learning curves of inexperienced readers, facilitate multicenter trials, and improve comparability of future studies.

To analyze the impact of functional magnetic resonance urography (fMRU) on the therapeutic management in infants with complex obstructive uropathy (OU) compared to the conventional diagnostic algorithm [CDA, ultrasound, radioisotope nephrography (RN)]. Retrospective analysis on 10 consecutive infants [female, n=3; male, n=7; age, 10.7 (2–17) months] with OU. Patients were examined according to CDA. If CDA revealed inconclusive results, fMRU was performed additionally. Split kidney function was assessed by RN [single kidney function (SKF)] and fMRU [volumetric differential renal function (vDRF)]. Findings were presented to an interdisciplinary truth-panel in a 2-step decision process (with and without fMRU). Clinical decision was determined. CDA indicated surgical intervention in 8 patients and conservative treatment in 2. Information by fMRU changed treatment strategy in 3 patients and led to the modification of the initially chosen surgical approach in 8 cases. The comparison of SKF and vDRF was not possible in 1 patient, whereas concordance was observed in 7 patients. SKF and vDRF differed >5% in 2 patients. fMRU has potential to improve therapeutic management of OU in infants. If surgical treatment is advised, the morphological information by fMRU has to be emphasized. Regarding kidney function estimation preliminary results are encouraging.