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In [In SPECT/CT phantom measurements (NaI cameras, N = 2; CZT, N = 1), peak contrast recovery (CRpeak) was derived from sphere inserts or myocardial insert (cardiac phantom; signal-to-background ratio [SBR], 10:1 or 5:1). In 25 positive and 38 negative patients (reference: endomyocardial biopsy or clinical diagnosis), Perugini scores and heart-to-contralateral (H/CL) count ratios were derived from planar images 1 hour and 3 hour p.i.In phantom measurements, accuracy of myocardial CRpeak at SBR 10:1 (H-mode, 0.95-0.99) and reproducibility at 5:1 (H-mode, 1.02-1.14) was comparable for H-mode and L-mode. However, L-mode showed higher variability of background counts and sphere CRpeak throughout the field of view than H-mode. In patients, sensitivity/specificity were ≥ 95% for H/CL ratios at both time points and visual scoring 3 hour. At 1 hour, visual scores showed specificity of 89% and reduced reader's confidence.Early DPD images provided no additional value for visual scoring or H/CL ratios. In SPECT/CT, H-mode is preferred over L-mode, especially if quantification is applied apart from the myocardium.ANTECEDENTES: En la gammagrafía con [ 99mTc]-DPD para amiloidosis cardiaca ATTR, se recomienda la adquisición de imágenes planares a las 3h p.i y SPECT/CT en modo L. Este estudio investigó si las imágenes planares más tempranas (1h p.i.) tienen beneficios y si la adquisición del SPECT/CT debería preferirse en modo H (ángulo de detección de 180 °) o en modo L (90 °). MéTODOS: En las mediciones con el fantoma del SPECT/CT (cámaras de NaI, n= 2; CZT, n=1), la recuperación pico de contraste (CRpico) se derivó de inserciones de esfera o de inserciones miocárdicas (fantoma cardiaco; relación señal-fondo [SBR], 10:1 o 5: 1). En 25 pacientes positivos y 38 negativos (referencia: biopsia endomiocárdica o diagnóstico clínico), el score de Perugini y la relación de cuentas corazón-contralateral (H/CL) se derivaron de imágenes planares a 1h y 3h p.i.En mediciones con el fantoma, la precisión del CRpico miocárdico en SBR 10:1 (modo H, 0.95-0.99) y la reproducibilidad a 5:1 (modo H, 1.02-1.14) fue comparable para el modo H y el modo L. Sin embargo, el modo L mostró una mayor variabilidad de las cuentas de fondo y del CRpico de la esfera en todo el campo de visión que el modo H. En pacientes, la sensibilidad/especificidad fue ≥ 95% para las relaciones H/CL en ambos puntos de tiempo y con un score visual a las 3 h. A 1h, los scores visuales mostraron una especificidad de (89%) y disminución de la confianza del lector.Las imágenes tempranas de DPD no proporcionaron ningún valor adicional para el score visual o las relaciones H/CL. En SPECT/CT, se prefiere el modo H sobre el modo L, especialmente si la cuantificación se aplica aparte del miocardio.摘要: 背景: [99mTc]Tc-DPD闪烁显像检查心肌ATTR淀粉样变性时, 建议使用3h p.i.平面图像和L模式SPECT/CT扫描。本研究探讨了早期平面图像(1h p.i.)是否有益, 以及SPECT/CT采集是否应首选H模式(探测器角度180°)或L模式(90°)。 方法: 在SPECT/CT模体测量中(NaI相机, n=2;CZT, n=1), 峰值造影剂恢复(CRpeak)来自球体插入物或心肌插入物(心脏模体; 信号与背景比[SBR], 10:1 或5:1)。在25个阳性和38个阴性病人中(参考标准: 心内膜活检或临床诊断), Perugini分数和心脏/对侧 (H / CL)计数比率来自平面图像1 h和3 h p.i.。 结果: 在模体测量中, 心肌CRpeak的SBR准确性 10:1 (H-mode, 0.95 - 0.99)和可重复性5:1 (H-mode, 1.02 - 1.14), H模式和L 模式相当。然而, 与H模式相比, L模式在整个视野中表现出更高的背景计数和球形CRpeak变异性。在患者中, 两个时间点的H/CL比值以及3h视觉评分的敏感性/特异性均≥95%。1h时, 视觉评分特异性为89%, 阅读者的信心降低。 结论: DPD早期图像对视觉评分和H/CL比值没有额外的价值。在SPECT/CT中, H模式优于L模式, 特别是心肌之外定量时。.

Background The introduction of hybrid SPECT/CT devices enables quantitative imaging in SPECT, providing a methodological setup for quantitation using SPECT tracers comparable to PET/CT. We evaluated a specific quantitative reconstruction algorithm for SPECT data using a 99mTc-filled NEMA phantom. Quantitative and qualitative image parameters were evaluated for different parametrizations of the acquisition and reconstruction protocol to identify an optimized quantitative protocol. Results The reconstructed activity concentration (ACrec) and the signal-to-noise ratio (SNR) of all examined protocols (n = 16) were significantly affected by the parametrization of the weighting factor k used in scatter correction, the total number of iterations and the sphere volume (all, p < 0.0001). The two examined SPECT acquisition protocols (with 60 or 120 projections) had a minor impact on the ACrec and no significant impact on the SNR. In comparison to the known AC, the use of default scatter correction (k = 0.47) or object-specific scatter correction (k = 0.18) resulted in an underestimation of ACrec in the largest sphere volume (26.5 ml) by − 13.9 kBq/ml (− 16.3%) and − 7.1 kBq/ml (− 8.4%), respectively. An increase in total iterations leads to an increase in estimated AC and a decrease in SNR. The mean difference between ACrec and known AC decreased with an increasing number of total iterations (e.g., for 20 iterations (2 iterations/10 subsets) = − 14.6 kBq/ml (− 17.1%), 240 iterations (24i/10s) = − 8.0 kBq/ml (− 9.4%), p < 0.0001). In parallel, the mean SNR decreased significantly from 2i/10s to 24i/10s by 76% (p < 0.0001). Conclusion Quantitative SPECT imaging is feasible with the used reconstruction algorithm and hybrid SPECT/CT, and its consistent implementation in diagnostics may provide perspectives for quantification in routine clinical practice (e.g., assessment of bone metabolism). When combining quantitative analysis and diagnostic imaging, we recommend using two different reconstruction protocols with task-specific optimized setups (quantitative vs. qualitative reconstruction). Furthermore, individual scatter correction significantly improves both quantitative and qualitative results.

Objectives In patients with NSCLC, current ESTS and ESMO guidelines recommend invasive lymph node (LN) staging with EBUS-TBNA even if FDG-PET/CT is negative for mediastinal LNs if at least one of three risk factors is present (cN1, non-peripheral primary or primary >3 cm). Modified workflows to avoid unnecessary invasive procedures were evaluated. Materials and methods Monocentric retrospective analysis of pretherapeutic FDG-PET/CT in 247 patients with NSCLC (62 % male; age, 68 [43–88] years) using an analog or digital PET/CT scanner. PET windowing was standardized. LNs were positive if ‘LN uptake > mediastinal blood pool’ or short axis >10 mm. Surgery or EBUS-TBNA served as reference for diagnostic accuracy per LN station. In all patients with negative mediastinal LNs by PET/CT, LN histology from surgery was available. Results Among 700 L N stations analyzed, 180 were malignant. Sensitivity and specificity of PET/CT per LN station were 93 % and 71 %. Following current guidelines, 76 patients with mediastinal negative PET/CT required confirmatory invasive staging. Only 5/76 patients had unexpected pN2 (all had adenocarcinoma). In a modified approach, confirmatory invasive staging was confined to patients with mediastinal negative PET/CT who showed all three risk factors. Using this modification, EBUS-TBNA could have been omitted in 62 (82 %) of the 76 patients who required EBUS-TBNA based on current recommendation. Among these 62 patients, only one patient had unsuspected pN2 (single-level) while the remaining 61 of 62 omitted EBUS-TBNA were deemed unnecessary because mediastinal LNs were confirmed to be negative. No multi-level pN2 would have been missed. Conclusion In the current analysis, 82 % of EBUS-TBNA procedures in patients with mediastinal negative PET/CT could have been omitted by modifying the current guideline workflow as proposed (i.e., restricting EBUS-TBNA in patients with cN0/1 to those with all three risk factors). This was consistent with different PET/CT scanners. Prospective confirmation is required.

Notwithstanding regulatory approval of lenvatinib and sorafenib to treat radioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC), important questions and controversies persist regarding this use of these tyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiary referral centers convened to identify and explore such issues; this paper summarizes their discussions. One challenge is determining when to start TKI therapy. Decision-making should be shared between patients and multidisciplinary caregivers, and should consider tumor size/burden, growth rate, and site(s), the key drivers of RAI-R DTC morbidity and mortality, along with current and projected tumor-related symptomatology, co-morbidities, and performance status. Another question involves choice of first-line TKIs. Currently, lenvatinib is generally preferred, due to greater increase in progression-free survival versus placebo treatment and higher response rate in its pivotal trial versus that of sorafenib; additionally, in those studies, lenvatinib but not sorafenib showed overall survival benefit in subgroup analysis. Whether recommended maximum or lower TKI starting doses better balance anti-tumor effects versus tolerability is also unresolved. Exploratory analyses of lenvatinib pivotal study data suggest dose-response effects, possibly favoring higher dosing; however, results are awaited of a prospective comparison of lenvatinib starting regimens. Some controversy surrounds determination of net therapeutic benefit, the key criterion for continuing TKI therapy: if tolerability is acceptable, overall disease control may justify further treatment despite limited but manageable progression. Future research should assess potential guideposts for starting TKIs; fine-tune dosing strategies and further characterize antitumor efficacy; and evaluate interventions to prevent and/or treat TKI toxicity, particularly palmar-plantar erythrodysesthesia and fatigue.

Objective Up to 60% of patients with metastatic, castration-resistant prostate cancer (mCRPC) treated with 177Lu prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) achieves a partial biochemical response with a decrease of > 50% in prostate-specific antigen (PSA) levels. The remaining fractions, however, do not respond to RLT. The aim of this explorative analysis was to identify pre-therapeutic factors for the prediction of response. Methods 46 patients [age = 68 years (50–87)] with mCRPC who consecutively underwent RLT with 177Lu PSMA [median applied activity = 6 GBq (2.9–6.2)] were included and analysed retrospectively. The association of different clinical and laboratory factors and parameters from pre-therapeutic 68Ga PSMA positron emission tomography (PET) with the outcome of RLT was tested (Fisher’s test). Outcome was defined as PSA changes 8 weeks after second RLT [partial response (PR), PSA decrease > 50%; progressive disease (PD), PSA increase ≥ 25%; stable disease (SD), others]. Significant predictive factors were combined in a predictive score. Results 30% showed a post-treatment PR (median 73% PSA decrease), 35% SD (median 17% PSA decrease) and 35% PD (median 42% PSA increase). Significant predictors for PD were alkaline phosphatase (ALP) > 135 U/l (p = 0.002), PSA > 200 ng/ml (p = 0.036), and maximum standardized uptake value (SUVmax) of the “hottest lesion” in pre-therapeutic PET p = 0.005). The predictive score including PSA, ALP and SUVmax could separate 2 distinct groups of patients: ≤ 2 predictive factors (19% PD) and 3 predictive factors (90% PD). Conclusion The presented predictive score allowed a pre-therapeutic estimate of the expected response to 2 cycles of RLT. As our study was retrospective, prospective trials are needed for validation.

Hereditary transthyretin amyloidosis (hATTR amyloidosis) is a multisystemic disease usually presenting in a mixed neurological and cardiological phenotype. We present a case of hATTR amyloidosis associated with Leu55Arg mutation causing a form of familial oculo-leptomeningeal amyloidosis. Two brothers and their mother presented with severe autonomic neuropathy, loss of visual acuity and lepto-meningeal involvement. One patient suffered subarachnoid hemorrhage as a possible complication of cerebral involvement. The patients suffered from treatment-refractory weight loss and recurring vitreous opacities. RNA interference-based treatment has led to stabilization of autonomic and peripheral neuropathy but has had no effect on ocular symptoms.

Background: Sorafenib for advanced hepatocellular carcinoma (HCC) is dose adjusted by toxicity. Preliminary studies have suggested an association between plasma concentrations of sorafenib and its main metabolite (M2) and clinical outcomes. This study aimed to validate these findings and establish target values for sorafenib trough concentrations. Methods: Patients with advanced HCC were prospectively recruited within a multicenter phase II study (SORAMIC). Patients with blood samples available at trough level were included for this pharmacokinetic (PK) substudy. Trough plasma concentrations of sorafenib and its main metabolite (M2) were associated with sorafenib-related toxicity and overall survival (OS). Results: Seventy-four patients were included with a median OS of 19.7 months (95% CI 16.1–23.3). Patients received sorafenib for a median of 51 weeks (IQR 27–62) and blood samples were drawn after a median of 25 weeks (IQR 10–42). Patients had a median trough concentration of 3217 ng/ml (IQR 2166–4526) and 360 ng/ml (IQR 190–593) with coefficients of variation of 65% and 146% for sorafenib and M2, respectively. Patients who experienced severe sorafenib-related toxicity received a lower average daily dose (551 vs 730 mg/day, p = .003), but showed no significant differences in sorafenib (3298 vs 2915 ng/ml, p = .442) or M2 trough levels (428 vs 283 ng/ml, p = .159). Trough levels of sorafenib or M2 showed no significant association with OS. Conclusions: In patients with advanced HCC treated with sorafenib, the administered dose, trough levels of sorafenib or M2, and clinical outcomes were poorly correlated. Toxicity-adjusted dosing remains the standard for sorafenib treatment.

Neck management in patients with early-stage, clinically node-negative oral squamous cell carcinoma (OSCC) remains a matter of discussion. Sentinel lymph node biopsy (SLNB) represents a treatment alternative to avoid elective neck dissection (END) in this cohort and different protocols and tracers exist. Here we present the clinical outcome of SLNB using 99mTc-tilmanocept in a two-day protocol in patients suffering from early-stage OSCC. A total of 13 patients (males: 6; females: 7; mean age: 65.7 years, ranging from 47 to 89 years) were included in this study. Most of the patients suffered from an OSCC of the floor of mouth (n = 6), followed by tongue (n = 5) and upper alveolar crest/hard palate (n = 2). Sentinel lymph nodes (SLNs) were successfully identified in all cases (range: 1–7). The average length of hospital stay was 4.7 days (range: 3–8 days) and mean duration of surgical intervention was 121 min (range: 74–233 min). One patient who suffered from an OSCC of the tongue was sentinel lymph node positive (SLN+). The mean follow-up for all sentinel lymph node negative (SLN-) patients (n = 12) was 20.3 months (range: 10–28 months). No local or nodal recurrences were observed within the observation period. In our patient cohort, SLNB using 99mTc-tilmanocept in a two-day protocol proved to be a reliable and safe staging method for patients suffering from early-stage, clinically node-negative OSCC. These results and their possible superiority to colloid tracers have to be confirmed in a prospective randomized controlled study.

Semiquantitative F-FET PET assessment using the tumor's SUV or tumor-to-background ratios (TBRs) can separate gliomas from peritumoral tissue or progression from pseudoprogression. This study investigated if point spread function (PSF) reconstruction of F-FET PET data affects SUV-based dignity assessment.This study is a retrospective analysis of 87 glioma patients (female, 36; male, 51; age, 48 [13-81] years) undergoing F-FET PET/MRI for staging (n = 17) or restaging (n = 70). PET was reconstructed using ordered-subset expectation maximization with and without PSF. Lesions were delineated with semiautomated background-adapted thresholding relative to SUVmax; background was delineated contralaterally. Comparative measurements with a National Electrical Manufacturers Association International Electrotechnical Commission PET body phantom (sphere-to-background ratios, 8:1 and 4:1) were performed.PSF showed significantly higher tumor SUVmax (median difference, +0.1; interquartile range, 0.04-0.18), SUVmean (+0.05; 0.03-0.08), TBRmax|mean (+0.1; 0.04-0.2), and TBRmean|mean (+0.06; 0.03-0.09) than non-PSF (P0.001). Background SUVmean was unaffected. In patients and phantom, differences between PSF and non-PSF increased with TBR and decreased with lesion's PET volume. Differences only exceeded 0.2 SUV for SUVmax or 0.1 SUV for SUVmean if TBR was greater than 3 and lesion's PET volume was less than 10 mL (d = 27 mm). Dignity assessment by PSF and non-PSF was concordant in all patients examined for staging (cutoff, TBRmean|mean1.6; positive, 14; negative, 3) and restaging (cutoff, TBRmax|mean2.0; positive, 67; negative, 3).PSF increased tumor SUVmax and SUVmean compared with non-PSF F-FET PET/MRI data, especially in small lesions with high TBR (3). However, dignity assessment using established TBR cutoffs was not affected.

Selective internal radiation therapy (SIRT) is a therapy option in patients with breast cancer liver metastasis (BCLM). This analysis aimed at identifying a prognostic score regarding overall survival (OS) after SIRT using routine pretherapeutic parameters. Retrospective analysis of 38 patients (age, 59 (39–84) years) with BCLM and 42 SIRT procedures. Cox regression for OS included clinical factors (age, ECOG and prior treatments), laboratory parameters, hepatic tumor load and dose reduction due to hepatopulmonary shunt. Elevated baseline ALT and/or AST was present if CTCAE grade ≥ 2 was fulfilled (&gt, 3 times the upper limit of normal). Median OS after SIRT was 6.4 months. In univariable Cox, ECOG ≥ 1 (hazard ratio (HR), 3.8), presence of elevated baseline ALT/AST (HR, 3.8), prior liver surgery (HR, 10.2), and dose reduction of 40% (HR, 8.1) predicted shorter OS (each p &lt, 0.05). Multivariable Cox confirmed ECOG ≥ 1 (HR, 2.34, p = 0.012) and elevated baseline ALT/AST (HR, 4.16, p &lt, 0.001). Combining both factors, median OS decreased from 19.2 months (0 risk factors, n = 14 procedures) to 5.9 months (1 factor, n = 20) or 2.2 months (2 factors, n = 8, 0.001). The proposed score may facilitate pretherapeutic identification of patients with unfavorable OS after SIRT. This may help to balance potential life prolongation with the hazards of invasive treatment and hospitalization.

Neuroendocrine tumors (NET) are rare and demonstrate variable clinical behavior depending on the degree of tumor differentiation. Patients with poorly differentiated tumors (NET G3) have a poor prognosis. Systemic treatment with cytotoxic chemotherapy is considered to be the treatment of choice. In patients that are refractory or intolerant to first-line therapy, experts recommend peptide receptor radionuclide therapy (PRRT) in tumors that express somatostatin receptors. Recently, combinations of PRRT and chemotherapy were tested in patients with NET. Available data have reported promising tumor control rates and an excellent toxicity profile in cases where PRRT had been administered with capecitabine/temozolomide, even when administered as salvage therapy. The current study reported an exceptional case of advanced NET G3 with severe toxicity upon receiving PRRT in combination with capecitabine/temozolomide as third line therapy. The patient developed a life-threatening neutropenic fever, fungal pneumonia and necrotizing mastitis 23 days after the first cycle of therapy was administered. However, the treatment led to a significant reduction in tumor size. A total of 5 months after treatment initiation, the patient was alive and in excellent clinical condition with sustained tumor response. In summary, the current study presented a rare case of high grade NET exhibiting an almost complete response to PRRT in combination capecitabine/temozolomide, despite facing unexpected severe toxicity.

We have investigated the prognostic value of two novel interim F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) parameters in patients undergoing chemoradiation (CRT) for esophageal squamous cell carcinoma (ESCC): one tumor parameter (maximal standardized uptake ratio rSUR) and one normal tissue parameter (change of FDG uptake within irradiated nontumor-affected esophagus increment SUVNTO). PET data of 134 European and Chinese patients were analyzed. Parameter establishment was based on 36 patients undergoing preoperative CRT plus surgery, validation was performed in 98 patients receiving definitive CRT. Patients received PET imaging prior and during fourth week of CRT. Clinical parameters, baseline PET parameters, and interim PET parameters (rSUR and increment SUVNTO) were analyzed and compared to event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM). Combining rSUR and increment SUVNTO revealed a strong prognostic impact on EFS, OS, LRC and FFDM in patients undergoing preoperative CRT. In the definitive CRT cohort, univariate analysis with respect to EFS revealed several staging plus both previously established interim PET parameters as significant prognostic factors. Multivariate analyses revealed only rSUR and increment SUVNTO as independent prognostic factors (p = 0.003, p = 0.008). Combination of these parameters with the cutoff established in preoperative CRT revealed excellent discrimination of patients with a long or short EFS (73% vs. 17% at 2 years, respectively) and significantly discriminated all other endpoints (OS, p < 0.001; LRC, p < 0.001; FFDM, p = 0.02), even in subgroups. Combined use of interim FDG-PET derived parameters increment SUVNTO and rSUR seems to have predictive potential, allowing to select responders for definitive CRT and omission of surgery.

Purpose[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) parameters have shown prognostic value in nasopharyngeal carcinomas (NPC), mostly in monocenter studies. The aim of this study was to assess the prognostic impact of standard and novel PET parameters in a multicenter cohort of patients.MethodsThe established PET parameters metabolic tumor volume (MTV), total lesion glycolysis (TLG) and maximal standardized uptake value (SUVmax) as well as the novel parameter tumor asphericity (ASP) were evaluated in a retrospective multicenter cohort of 114 NPC patients with FDG-PET staging, treated with (chemo)radiation at 8 international institutions. Uni- and multivariable Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), event-free survival (EFS), distant metastases-free survival (FFDM), and locoregional control (LRC) was performed for clinical and PET parameters.ResultsWhen analyzing metric PET parameters, ASP showed a significant association with EFS (p = 0.035) and a trend for OS (p = 0.058). MTV was significantly associated with EFS (p = 0.026), OS (p = 0.008) and LRC (p = 0.012) and TLG with LRC (p = 0.019). TLG and MTV showed a very high correlation (Spearman's rho = 0.95), therefore TLG was subesequently not further analysed. Optimal cutoff values for defining high and low risk groups were determined by maximization of the p-value in univariate Cox regression considering all possible cutoff values. Generation of stable cutoff values was feasible for MTV (p55 years + one binarized PET parameter), MTV >11.1ml (hazard ratio (HR): 3.57, p 14.4% (HR: 3.2, p = 0.031) remained prognostic for OS. MTV additionally remained prognostic for LRC (HR: 4.86 pConclusionsIn this analysis, PET parameters were associated with outcome of NPC patients. MTV showed a robust association with OS, EFS and LRC. Our data suggest that combination of MTV and ASP may potentially further improve the risk stratification of NPC patients.

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel–Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10–75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P P = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

Summary Objectives: Low-dose-computed tomography (LD-CT) is used in nuclear medicine hybrid imaging (e.g., SPECT/CT) for attenuation correction of emission data and anatomical correlation of findings. However, there are currently no standards for image quality (e. g., detectability) comparable to those for diagnostic CT. Therefore, the aim of this explorative study was to evaluate retrospective LDCT data in terms of CT image quality and detectability of anatomical structures. Methods: Two readers blindly scored abdominal LD-CT images (n = 40 patients) in terms of detectability (n = 20 structures/patient), image quality, and readers’ confidence in scoring the image quality for a clinically hybrid imaging protocol. Results were analysed by ANOVA to identify factors (e. g., anatomical structures) that influenced performance scores. The inter-rater agreement was evaluated by determining the chance-corrected Cohen’s Kappa coefficient. Results: Image noise was acceptable for anatomical correlation in 96.1 % of the readings with an almost perfect inter-rater agreement (KBP = 0.85). A detectability of at least 80 % was observed in 13/20 (KBP ≥ 0.7) and 90 % in 9/20 (KBP ≥ 0.85) of the structures analysed by both readers. The confidence of both readers in scoring image quality was at least sufficient in 98.8 % of the examined patients (KBP = 0.95). Conclusion: Although LD-CT protocols commonly used in hybrid imaging have a poor image quality not suitable for primary CT diagnostics, they enable detection of a variety of anatomical structures. LDCT can therefore also be referenced in the associated reports for anatomical correlation of findings from SPECT imaging.

ZusammenfassungDie vorliegende Handlungsempfehlung dient als Grundlage zur Qualitätssicherung der Somatostatinrezeptor (SSTR-) PET/CT bei onkologischen Patienten. Die Leitlinie wurde interdisziplinär erarbeitet und enthält neben der Definition und Zielsetzung einen Konsens hinsichtlich der erforderlichen klinischen Hintergrundinformationen, Indikationsstellung, Durchführung, Auswertung, Dokumentation und Befunderstellung. Dabei werden die beiden gebräuchlichsten Radiotracer der SSTRPET/ CT (68Ga-DOTATOC und 68Ga-DOTATATE) vertieft dargestellt. Die SSTR-PET/CT erfordert eine enge Interaktion zwischen den zuweisenden und ausführenden Fachdisziplinen unter Berücksichtigung bereits vorhandener Leitlinien und Handlungsempfehlungen europäischer und deutscher Fachgesellschaften, namentlich der European Association of Nuclear Medicine (EANM), der Deutschen Gesellschaft für Endokrinologie (DGE), Deutschen Gesellschaft für Nuklearmedizin (DGN) und Deutschen Röntgengesellschaft (DRG).

SummaryAim: According to German guidelines, I-123-MIBG scintigraphy in neuroblastoma (NB) is preferably performed as early (about 4 h p.i.) and late (24 h p.i.) planar imaging and single- photon emission computed tomography (SPECT) or SPECT/CT 24 h p.i. This study evaluated if the work-up could be reduced to a single timepoint.Methods: Retrospective analysis of 37 examinations in 26 patients (f:8; m:18; age, 0.5–23.5a) with NB (initial, 15; restaging, 22). All 74 (early + late) pairs of ventral/dorsal planar whole-body images were reviewed by 3 independent readers in random order blinded to clinical data (1, certainly physiological; 2, likely physiological; 3, likely malignant; 4, certainly malignant). CT/MRI or SPECT served as standard of reference if planar images were equivocal.Results: Two-hundred malignant lesions were rated (1–23 lesions per examination). The lesions’ mean score was higher at late vs. early imaging for all readers (3.6 vs. 3.4, 3.7 vs. 3.2, 3.5 vs. 3.2; each p < 0.01). Fifty-one lesions (25.5 %) were considerably underrated at early vs. late imaging (score difference ≥2) by any reader (29/153 skeletal lesions, 12/28 primary tumors [PT], 10/18 abdominal lymph nodes [LN]). Early image did not detect any lesion in 6 patients with PT only. In contrast, 9 lesions (4.5 %) were underrated by late vs. early imaging: 5 skeletal lesions (pelvis, 2; femoral shaft, 3), 1 PT, 3 LN, and 0/1 liver lesions. Tumor spread was underestimated thereby at late vs. early imaging in 1 patient (LN) but SPECT was correct.Conclusion: The early planar image provided no relevant information over the late image in any patient and may only be performed after weighting of risks (stress) and benefits – especially if SPECT or SPECT/CT is routinely performed. Vice versa, early planar image alone does not suffice.

In radioembolic therapy (RET) of hepatic malignancies using yttrium-90 (Y)-labeled resin microspheres, radiation protection is primarily concerned with avoiding contamination by radioactive spheres. However, as Y is bound to the microsphere surface by a potentially reversible ion-exchange process, the aim of this study was to assess the extent of the potential excreted activity in urine. After RET with Y-labeled resin-based microspheres, urinary excretion of free Y was prospectively analyzed in 51 interventions (n = 45 patients) by sampling urine over 48 h (two 24-h intervals) consecutively. The measured urinary concentration of Y, normalized to the administered microsphere activity, was a median of 58.5 kBq L GBq (range = 3.5-590.9 kBq L GBq) and 17.8 kBq L GBq (1.8-58.8 kBq L GBq) for the first and second 24-h periods after administration, respectively (p ≤ 0.0001, F = 28.4, result from ANOVA). The total excreted activity significantly decreased (p ≤ 0.0001) from a median of 72.5 kBq in the first 24-h period to a median of 22.1 kBq in the second 24-h period. Urinary excretion of free Y after resin-based RET occurs for a longer period and at a higher activity excretion than previously published, which has to be considered when patients are either hospitalized or return home after RET. Existing approaches for patient hospitalization, especially in temporary radiation protection areas, justified by the previously reported lower excretion rate, should be re-evaluated, and as a consequence, the current product safety information and handling recommendations for Y-labeled resin-based microspheres may need to be revised.

Purpose Dopamine transporter SPECT with I-FP-CIT is registered for detection (or exclusion) of nigrostriatal degeneration to support the etiologic classification of parkinsonian syndromes. In case of uncertainty in the interpretation of SPECT findings or unexpected clinical course, follow-up SPECT might be useful. However, the utility of follow-up FP-CIT SPECT has not yet been clarified. Methods One hundred forty-one patients (65.1 ± 10.4 years) from 3 sites with follow-up FP-CIT SPECT 22.4 ± 13.7 months after baseline SPECT were included. Retrospective visual interpretation of FP-CIT SPECT scans was performed by 2 experienced readers according to the following 7-point score: "normal," some minor degree of uncertainty due to "mild asymmetry" or mild to moderate "uniform reduction," "Parkinson disease (PD) reduction type 1/2/3," and "atypical reduction." Results Normal FP-CIT SPECT or PD characteristic reduction was confirmed by follow-up SPECT in all cases (n = 58). Among patients with some minor degree of uncertainty at baseline (n = 65), the majority (72%) did now show abnormalities in follow-up SPECT, but 20% showed clear progression suggesting nigrostriatal degeneration. The latter was very rare at age younger than 60 years. The final categorization as normal or neurodegenerative was not affected by the time delay between baseline and follow-up SPECT. Conclusions Follow-up FP-CIT SPECT cannot be generally recommended in case of completely normal baseline SPECT or PD characteristic reduction. It also cannot be recommended in patients younger than 60 years, even in case of some minor degree of uncertainty in the baseline SPECT. There is no evidence to delay follow-up FP-CIT SPECT longer than 12 months.

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.

To evaluate the course of pro- and anti-inflammatory cytokines after 90Y-radioembolization (RE) of liver malignancies and to identify prognosticators for liver-related adverse events and survival. In 34 consecutive patients with secondary or primary liver tumors scheduled for RE, the following cytokines were measured prior to and 2 h, 3 days, and 6 weeks after RE: interleukin (IL) -1, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and interferon-γ. Liver function impairment was defined as an elevation of liver-related laboratory values as graded by CTCAE ≥ 2 and/or serum bilirubin ≥30 µmol/l and/or development of ascites at 6-week follow-up. Significant changes over time were seen in IL-1 (increase from 0.4 pg/ml (±0.7) at baseline to 1.1 pg/ml (±1.4) 3 days after RE (p = 0.02)), and in IL-6 (increase from 16.8 pg/ml (±21.8) at baseline to 54.6 pg/ml (±78.2) 3 days after RE (p = 0.003)). Baseline values of IL-6 and IL-8 were independently associated with liver function impairment at follow-up as well as decreased survival with an optimal cutoff at 6.53 and 60.8 pg/ml, respectively. Expected changes in pro- and anti-inflammatory cytokines after RE were shown. Furthermore, baseline values of IL-6 and IL-8 were associated with later liver dysfunction and survival. We hypothesize that these biomarkers are potential prognosticators and might help in patient selection for RE.

Increased expression of neurotensin receptor 1 (NTR1) has been shown in a large number of tumor entities such as pancreatic or colon carcinoma. Hence, this receptor is a promising target for diagnostic imaging and radioligand therapy. Using the favorable biodistribution data of the NTR1-targeting agent 111In-3BP-227, we investigated the therapeutic effect of its 177Lu-labeled analog on the tumor growth of NTR1-positive HT29 colon carcinoma xenografts. Methods: 3BP-227 was labeled with 177Lu. To assess its biodistribution properties, SPECT and CT scans of HT29-xenografted nude mice injected with 177Lu-3BP-227 were acquired, and ex vivo tissue activity was determined. To evaluate therapeutic efficacy, 2 groups of mice received the radiopharmaceutical in a median dose of either 165 MBq (129-232 MBq, n = 10) or 110 MBq (82-116 MBq, n = 10), whereas control mice were injected with vehicle (n = 10). Tumor sizes and body weights were monitored for up to 49 d. Renal function and histologic morphology were evaluated. Results: Whole-body SPECT/CT images allowed clear tumor visualization with low background activity and high tumor-to-kidney and -liver ratios. Ex vivo biodistribution data confirmed high and persistent uptake of 177Lu-3BP-227 in HT29 tumors (19.0 ± 3.6 vs. 2.7 ± 1.6 percentage injected dose per gram at 3 and 69 h after injection, respectively). The application of 177Lu-3BP-227 resulted in a distinct delay of tumor growth. Median tumor doubling time for controls was 5.5 d (interquartile range [IQR], 2.8-7.0), compared with 17.5 d (IQR, 5.5-22.5 d) for the 110-MBq and 41.0 d (IQR, 27.5-55.0) for the 165-MBg group. Compared with controls, median relative tumor volume at day 23 after injection was reduced by 55% (P = 0.034) in the 110-MBq and by 88% (P < 0.01) in the 165-MBq group. Renal histology and clinical chemistry results did not differ between radiotherapy groups and controls, suggesting absence of therapy-induced acute renal damage. Conclusion: These data demonstrate that the novel NTR1-targeting theranostic agent 3BP-227 is an effective and promising candidate for radioligand therapy, with a favorable preliminary safety profile and high potential for clinical translation.

The objective of this study was to assess the influence of an iterative CT reconstruction algorithm (IA), newly available for CT-fluoroscopy (CTF), on image noise, readers’ confidence and effective dose compared to filtered back projection (FBP). Data from 165 patients (FBP/IA = 82/74) with CTF in the thorax, abdomen and pelvis were included. Noise was analysed in a large-diameter vessel. The impact of reconstruction and variables (e.g. X-ray tube current I) influencing noise and effective dose were analysed by ANOVA and a pairwise t-test with Bonferroni–Holm correction. Noise and readers’ confidence were evaluated by three readers. Noise was significantly influenced by reconstruction, I, body region and circumference (all p ≤ 0.0002). IA reduced the noise significantly compared to FBP (p = 0.02). The effect varied for body regions and circumferences (p ≤ 0.001). The effective dose was influenced by the reconstruction, body region, interventional procedure and I (all p ≤ 0.02). The inter-rater reliability for noise and readers’ confidence was good (W ≥ 0.75, p

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.

ZusammenfassungThese guidelines aim to support medical personnel and physicians working in oncology in selecting appropriate patients, in treatment planning, preparation and implementation of SIRT for the treatment of primary and secondary liver malignancies. The focus lies on the requirements in the treatment center with regard to staffing, technical, and organizational aspects including radiation safety. Patient selection need to be performed in an interdisciplinary tumor board including the medical team tasked with the treatment and a medical physics expert. The aims of the treatment, the workup necessary for patient selection and treatment planning, and for avoiding complications are presented as are the requirements for obtaining informed consent from the patient. The follow-up of patients after SIRT also requires interdisciplinary cooperation, including communication with the local family physician.

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.

BACKGROUND & AIMS: Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the efficacy and safety of a combination of sorafenib and selective internal radiation therapy (SIRT) - with yttrium-90 (90Y) resin microspheres - to sorafenib alone in patients with advanced HCC. METHODS: SORAMIC is a randomised controlled trial comprising diagnostic, local ablation and palliative cohorts. Based on diagnostic study results, patients were assigned to local ablation or palliative cohorts. In the palliative cohort, patients not eligible for TACE were randomised 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. The primary endpoint was overall survival (OS; Kaplan-Meier analysis) in the intention-to-treat (ITT) population. RESULTS: In the ITT cohort, 216 patients were randomised to SIRT + sorafenib and 208 to sorafenib alone. Median OS was 12.1 months in the SIRT + sorafenib arm, and 11.4 months in the sorafenib arm (hazard ratio [HR] 1.01; 95% CI 0.81-1.25; p = 0.9529). Median OS in the per protocol population was 14.0 months in the SIRT + sorafenib arm (n = 114), and 11.1 months in the sorafenib arm (n = 174; HR 0.86; p = 0.2515). Subgroup analyses of the per protocol population indicated a survival benefit of SIRT + sorafenib for patients without cirrhosis (HR 0.46; 0.25-0.86; p = 0.02); cirrhosis of non-alcoholic aetiology (HR 0.63; p = 0.012); or patients ≤65 years old (HR 0.65; p = 0.05). Adverse events (AEs) of Common Terminology Criteria for AE Grades 3-4 were reported in 103/159 (64.8%) patients who received SIRT + sorafenib, 106/197 (53.8%) patients who received sorafenib alone (p = 0.04), and 8/24 (33.3%) patients who only received SIRT. CONCLUSION: Addition of SIRT to sorafenib did not result in a significant improvement in OS compared with sorafenib alone. Subgroup analyses led to hypothesis-generating results that will support the design of future studies. LAY SUMMARY: Sorafenib given orally is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). In selective internal radiation therapy (SIRT), also known as radioembolisation, microscopic, radioactive resin or glass spheres are introduced into the blood vessels that feed the tumours in the liver. This study found that the addition of SIRT with 90yttrium-loaded resin microspheres to sorafenib treatment in people with advanced HCC did not significantly improve overall survival compared with sorafenib treatment alone. However, the results give an indication of how future studies using this combination therapy in people with advanced HCC could be designed. STUDY REGISTRATION: EudraCT 2009-012576-27, NCT0112 6645. ispartof: JOURNAL OF HEPATOLOGY vol:71 issue:6 pages:1164-1174 ispartof: location:Netherlands status: published

Sufficient glomerular filtration rate (GFR) is mandatory in living kidney donors (LKD) before renal transplantation (RT). Guidelines recommend exogenous GFR (e. g. Tc-99m-DTPA) besides estimated GFR by plasma creatinine (eGFR). Tc-99m-MAG3 determines split function and tubular extraction rate (TER). This study evaluated a time-efficient one-day protocol for DTPA and MAG3 in potential LKD. Retrospective analysis of 82 consecutive potential LKD (female, 52; age, 54 [19-73] a). DTPA GFR (Fleming formula) with blood sampling 169 (147-205) min post injection of 27 (18-59) MBq Tc-99m-DTPA. 199 (181-219) min after DTPA injection, same-day renal scintigraphy with 105 (65-150) MBq MAG3 followed (TER according to Bubeck). Sufficient GFR for RT was defined age- and sex-dependent based on British guidelines, normal TER at 70 % of age-dependent average. In 15 separate potential LKD, a blank blood sample before MAG3 injection allowed estimation of remaining DTPA counts and resulting TER error. Remaining Tc-99m-DTPA blood counts during sampling for MAG3 led to median TER underestimation by 12 (IQR, 8-15) ml/min/1.73 m A one-day protocol for Tc-99m-DTPA GFR and MAG3 dynamic imaging is feasible. If TER is calculated, the proposed method for blood count correction may be applied. However, relevance of the TER remains questionable due to frequent discordance to GFR.ZIEL: Eine ausreichende glomeruläre Filtrationsrate (GFR) vor Nierenspende (RT) ist Voraussetzung für Lebendspender (LKD). Leitlinien empfehlen exogene Methoden der GFR-Bestimmung (z. B. Tc-99m-DTPA) neben der geschätzten GFR aus Plasmakreatinin (eGFR). Tc-99m-MAG3 dient der Bestimmung der getrennten Seitenfunktion und tubulären Extraktionsrate (TER). Diese Studie untersuchte ein zeitsparendes 1-Tages-Protokoll für DTPA und MAG3 bei potenziellen LKD. Retrospektive Analyse von 82 konsekutiven potenziellen LKD (Frauen: 52; Alter: 54 (19–73) Jahre). DTPA-GFR (Fleming-Formel) mit Blutentnahmen 169 (147–205) min p. i. von 27 (18–59) MBq-Tc-99m-DTPA. Eine taggleiche Nierenszintigrafie mit 105 (65–150) MBq-MAG3 folgte (TER nach Bubeck). Ausreichende GFR vor RT wurde alters- und geschlechtsabhängig nach britischen Leitlinien definiert, normale TER als ≥ 70 % der Altersnorm. Bei 15 separaten potenziellen LKD erlaubte eine zusätzliche Blutentnahme vor MAG3-Injektion die Abschätzung der verbliebenen DTPA-Counts und des resultierenden TER-Fehlers. Verbliebene Tc-99m-DTPA-Counts zur Zeit der MAG3-Blutentnahme bewirkten eine mediane TER-Unterschätzung um 12 (IQR, 8–15) ml/min/1,73 m Ein 1-Tages-Protokoll für Tc-99m-DTPA-GFR und MAG3-Nierenszintigrafie ist möglich. Wenn eine TER-Bestimmung beabsichtigt ist, kann die vorgeschlagene Blutcount-Korrektur erfolgen. Jedoch bleibt der Stellenwert der TER aufgrund der häufigen Diskordanz zur GFR fraglich.

Background Iterative computed tomography (CT) image reconstruction shows high potential for the preservation of image quality in diagnostic CT while reducing patients’ exposure; it has become available for low-dose CT (LD-CT) in high-end hybrid imaging systems (e.g. single-photon emission computed tomography [SPECT]-CT). Purpose To examine the effect of an iterative CT reconstruction algorithm on image quality, image noise, detectability, and the reader’s confidence for LD-CT data by a subjective assessment. Material and Methods The LD-CT data were validated for 40 patients examined by an abdominal hybrid SPECT-CT (U = 120 kV, I = 40 mA, pitch = 1.375). LD-CT was reconstructed using either filtered back projection (FBP) or an iterative image reconstruction algorithm (Adaptive Statistical Iterative Reconstruction [ASIR]®) with different parameters (ASIR levels 50% and 100%). The data were validated by two independent blinded readers using a scoring system for image quality, image noise, detectability, and reader confidence, for a predefined set of 16 anatomic substructures. Results The image quality was significantly improved by iterative reconstruction of the LD-CT data compared with FBP ( P ≤ 0.0001). While detectability increased in only 2/16 structures ( P ≤ 0.03), the reader’s confidence increased significantly due to iterative reconstruction ( P ≤ 0.002). Meanwhile, at the ASIR level of 100%, the detectability in bone structure was highly reduced ( P = 0.003). Conclusion An ASIR level of 50% represents a good compromise in abdominal LD-CT image reconstruction. The specific ASIR level improved image quality (reduced image noise) and reader confidence, while preserving detectability of bone structure.

Ziel/Aim: In patients with non-small cell lung cancer (NSCLC) undergoing treatment with curative intent, the asphericity (ASP) of the primary tumor’s metabolic tumor volume (MTV) has been demonstrated as a prognostic factor. This study aimed at validation in an independent cohort with sufficient sample size. Methodik/Methods: Retrospective study in 313 NSCLC patients (203 men; median age, 67 [41-87] a) undergoing FDG-PET/CT with the same scanner prior to treatment in curative intent (always including resection of the primary tumor). 137 patients had UICC stage I, 79 patients stage II and 97 patients stage III disease (adenocarcinoma [ADC], 153; squamous cell carcinoma [SCC], 143, other, 17). Delineation of primary tumor MTV with semiautomated background-adapted threshold relative to its SUVmax. Univariable Cox regression for progression-free (PFS) and overall survival (OS) for PET parameters (MTV, ASP, SUVmax, SUVmean), clinical (UICC stage I vs. II vs. III), histological (SCC vs. ADC) and treatment variables (Rx/1 vs. R0 resection, chemotherapy yes/no, radiotherapy yes/no). Multivariable Cox of parameters significant in univariate Cox. Ergebnisse/Results: Events (progression, relapse, death) occurred in 169/313 patients, 139 patients died (median follow-up in survivors, 37 months). In multivariable Cox for OS, ASP >33.3% (hazard ratio [HR], 1.53 [95%-confidence interval, 1.02-2.3]), Rx/1 vs. R0 resection (HR, 2.47 [1.5-4.2]) and SCC vs. ADC (HR, 1.53 [1.1-2.2]) were significant. Log-rank test for ASP was significant at any cut-off from 18% upwards. Among separate UICC stages, ASP was only prognostic for OS in stage II (optimal, >19.5%; median OS, 33 vs. 59 months; p21.2% (HR, 1.75 [1.2-2.5]) and Rx/1 vs. R0 (HR, 2.48 [1.5-4.1]) were significant. Log-rank test for ASP was significant at any cut-off from 10-60%. Schlussfolgerungen/Conclusions: ASP was validated as an independent predictor of PFS and OS in NSCLC patients with curative treatment intent. Subdividing UICC stages, ASP remained prognostic in stage II.

Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients, Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP], n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP), n = 34). The primary endpoint was toxicity including symptoms of RILD, Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but &lt, 30 μmol/L), severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34, p = 0.140). Severe RILD occurred in the SP group only (n = 2, p &gt, 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant), Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

Asphericity (ASP) is a tumour shape descriptor based on the PET image. It quantitates the deviation from spherical of the shape of the metabolic tumour volume (MTV). In order to identify its biological correlates, we investigated the relationship between ASP and clinically relevant histopathological and molecular signatures in non-small-cell lung cancer (NSCLC).The study included 83 consecutive patients (18 women, aged 66.4 ± 8.9 years) with newly diagnosed NSCLC in whom PET/CT withSUVmax, MTV and ASP were associated with pathological T stage (Kruskal-Wallis, p = 0.001, p 0.0005 and p 0.0005, respectively) and N stage (p = 0.017, p = 0.003 and p = 0.002, respectively). Only ASP was associated with M stage (p = 0.026). SUVmax, MTV and ASP were correlated with Ki-67 index (Spearman's rho = 0.326/p = 0.003, rho = 0.302/p = 0.006 and rho = 0.271/p = 0.015, respectively). The latter correlations were considerably stronger in adenocarcinomas than in squamous cell carcinomas. ASP, but not SUVmax or MTV, showed a tendency for a significant association with the extent of VEGF expression (p = 0.058). In multivariate Cox regression analysis, ASP (p 0.0005) and the presence of distant metastases (p = 0.023) were significantly associated with progression-free survival. ASP (p = 0.006), the presence of distant metastases (p = 0.010), and Ki-67 index (p = 0.062) were significantly associated with overall survival.The ASP of primary NSCLCs on FDG PET images is associated with tumour dimensions and molecular markers of proliferation and angiogenesis.

Background This study evaluates bone remodeling processes in the proximal humerus induced by the implantation of a stemless shoulder prosthesis with regard to time of response and type and extent of bone turnover. Methods Twenty-eight patients with primary osteoarthritis of the shoulder undergoing a stemless shoulder arthroplasty were prospectively evaluated. The local metabolic bone activity in 5 regions of interest (ROIs 1-5) around the implant and in 1 reference region (ROI ref.) in the humeral diaphysis was analyzed after the application of technetium Tc 99m DPD using single-photon emission computed tomography integrated with multidetector computed tomography (SPECT/CT). The study cohort was divided into 4 groups according to the timing of the most recent follow-up appointment to evaluate the primary osseointegrative response after surgery. The bone uptake values were expressed in target (ROIs 1-5) to nontarget (ROI ref.) ratios. Results No difference within the 4 subgroups with respect to the time of local metabolic bone activity in the ROIs was found at 90 days after surgery. The highest initial metabolic activity and most temporal modifications were found in ROI 1, which was localized in the superior segment of the stem. Conclusions SPECT/CT data suggest that the primary osseointegration of a stemless shoulder prosthesis is almost completed 3 months after implantation. Variations in metabolic activity pattern in the ROIs during follow-up may be caused by different loading conditions of the bone.

Background In patients with non–small-cell lung cancer (NSCLC), asphericity (ASP) of the primary tumor’s metabolic tumor volume (MTV) has shown prognostic significance. This study aimed at validation in an independent and sufficiently large cohort. Patients and Methods A retrospective study was performed of 311 NSCLC patients undergoing 18F-fluorodeoxyglucose positron emission tomography / computed tomography (18F-FDG PET/CT) before curatively intended treatment (always including surgery). A total of 140 patients had International Union Against Cancer (UICC) stage I disease, 78 had stage II disease, and 93 had stage III disease (adenocarcinoma, n = 153; squamous-cell carcinoma, n = 141). Primary tumor MTV was delineated with semiautomated background-adapted threshold relative to the standardized maximum uptake value (SUVmax). Cox regression (progression-free survival [PFS] and overall survival [OS]) analysis for positron emission tomography (MTV, ASP, SUVmax) as well as for clinical (T/N descriptor, UICC stages), histologic, and treatment variables (Rx/1 vs. R0 resection, chemotherapy/radiotherapy yes/no) were performed. Results Events (progression and relapse) occurred in 167 of 311 patients; 137 died (median survivor follow-up, 37 months). In multivariable Cox regression for OS, ASP > 33.3% (hazard ratio, 1.58 [1.04-2.39]), male sex (1.84), age (1.04 per year), Eastern Cooperative Oncology Group performance status ≥ 2 versus 0/1 (2.68), stage II versus I (1.96), and Rx/1 versus R0 resection (2.1) were significant. Among separate UICC stages, ASP only predicted OS in stage II (optimal, > 19.5%; median OS, 33 vs. 59 months). Regarding PFS, ASP > 21.2%, male sex, Eastern Cooperative Oncology Group performance status ≥ 2, stage II versus I disease, and Rx/1 resection were prognostic. ASP remained prognostic for stage II disease (optimal, > 19.5%; PFS, 12 vs. 47 months). Log-rank test for ASP was significant at any cutoff ≥ 18% (OS) or from 9% to 59% (PFS). Conclusion ASP was validated as prognostic factor for PFS and OS in patients with NSCLC and curative treatment intent, especially stage II. High ASP in stage II could imply intensified treatment or intensified follow-up.

To evaluate the accuracy of clinical parameters and established pre-treatment risk stratification systems for prostate cancer (PCa) in predicting PSMA-positive metastases in men undergoing Ga-68-PSMA PET/CT as initial staging examination.A retrospective analysis in 108 consecutive treatment-naïve patients with biopsy-proven PCa undergoing Ga-68-PSMA PET/CT (median age, 72 years [range, 49-82 years]) was performed. Prediction of PSMA-positive metastases by serum PSA, clinical T stage (cT), ISUP group, percentage of positive biopsy cores, and derived risk scores (D'Amico risk classification system, Roach [RF], Yale formula [YF], and Briganti nomogram [BN]) was examined with ROC analysis.Any PSMA-positive metastases were found in 36 of 108 patients, including LN metastases in 28 patients, extrapelvic LN metastases in 15 patients, and organ metastases in 19 patients (bone, 19; lung, 1). AUCs for PSA, cT, ISUP, and percentage of positive biopsy cores regarding PSMA-positive metastases did not differ significantly (range, 0.6-0.8; each P 0.05). D'Amico (AUC, 0.61-0.64) was inferior to RF (0.76-0.83), YF (0.81-0.86), and BN (0.73 to 0.88; each P 0.05). Among the 89 high-risk patients (D'Amico), decision for or against PET imaging based on RF (cut-off,18.0), YF (10.8), or BN (8.0) would have prevented PSMA PET/CT in 4 (5%), 15 (17%), or 18 patients (20%), respectively, while preserving a sensitivity ≥95% for PSMA-positive metastases.Clinical parameters and established risk stratification systems for PCa can predict Ga-68-PSMA PET-positive metastases in treatment-naïve patients. Especially YF and BN may improve identification of patients with the highest probability of metastatic disease detected by Ga-68-PSMA PET/CT.

This prospective study compared a 1-d SPECT/CT protocol with the commonly used 3-d protocol for somatostatin receptor scintigraphy in patients with gastroenteropancreatic neuroendocrine neoplasms. Additionally, the influence of SPECT/CT on patient management was evaluated. Methods: From October 2011 to October 2012, all gastroenteropancreatic neuroendocrine neoplasm patients undergoing restaging with somatostatin receptor scintigraphy on a modern SPECT/CT device were enrolled in this study. The protocol consisted of planar imaging at 4, 24, and 48 h; low-dose SPECT/CT at 24 and 48 h; diagnostic CT at 24 h using a triple-phase delay after administration of contrast; and diagnostic SPECT/CT at 24 h. All components of the imaging data were reassessed by 3 masked interpreters. The results were compared with a reference standard based on all clinical, imaging, and histopathology follow-up data available (follow-up range, 24–36 mo; mean, 29.9 mo). The reference standard was defined by a study-specific interdisciplinary tumor board that also reassessed treatment decisions. Results: Thirty-one patients were eligible for analysis (18 men and 13 women; mean age, 60.4 y). Ten had no imaging signs of disease and remained disease-free during follow-up. Twenty-one had persistent or recurrent disease (82 lesions: 24 in the liver, 21 in the lymph nodes, 16 in bone, 12 in the pancreas, and 9 in other locations). The respective lesion detection rates for interpreters 1, 2, and 3 were 51.9%, 49.4%, and 71.6% for low-dose SPECT/CT at 24 h; 51.9%, 55.6%, and 67.9% for low-dose SPECT/CT at 48 h; 63.0%, 70.4%, and 85.2% for diagnostic CT; and 77.8%, 84.0%, and 88.9% for diagnostic SPECT/CT. Interobserver agreement was moderate for diagnostic SPECT/CT (κ = 0.44), diagnostic CT (κ = 0.43), low-dose SPECT/CT at 48 h (κ = 0.61), and low-dose SPECT/CT at 24 h (κ = 0.55). For planar imaging, interobserver agreement was fair after 48 h (κ = 0.36) and 24 h (κ = 0.38) and moderate after 4 h (κ = 0.42). Every lesion detectable on planar imaging or low-dose SPECT/CT was also detectable on diagnostic SPECT/CT. The CT and SPECT components of diagnostic SPECT/CT strongly complemented each other, as 34 of 82 lesions (41.4%) were detected on only the CT component or only the SPECT component. Therapeutic management was influenced by the diagnostic SPECT/CT interpretation in 8 of 31 patients (25.8%). Conclusion: The highest detection rates were achieved by diagnostic SPECT/CT. Thus, a more patient-friendly 1-d protocol is feasible. Furthermore, multiphase SPECT/CT affected management in about a quarter of patients.

To analyze the diagnostic performance of dual time point imaging (DTPI) for pre-therapeutic lymph node (LN) staging in non-small cell lung cancer (NSCLC). This was a retrospective analysis of 47 patients with NSCLC who had undergone DTPI by PET (early + delayed) using F18-fluorodeoxyglucose (FDG). PET raw data were reconstructed iteratively (point spread function + time-of-flight). LN uptake in PET was assessed visually (four-step score) and semi-quantitatively (SUVmax, SUVmean, ratios LN/primary, LN/liver, and LN/mediastinal blood pool). DTPI analyses included retention indices (RIs), Δ-ratios and changes in visual score. Histology or cytology served as standards of reference. Accuracy was determined based on ROC analyses. Thirty-six of 155 LNs were malignant. DTPI accuracy was low for all measures (visual assessment, 24.5%; RI SUVmax, 68.4%; RI SUVmean, 65.8%; Δ-ratios, 63.9-76.1%) and significantly inferior to early PET. Accuracies of early (range, 86.5–92.9%) and delayed PET (range, 85.2–92.9%) were comparable. At early PET, accuracy of the visual score (92.9%) was similar or superior to semi-quantitative analyses (range, 86.5–92.3%). Using a modern PET/CT device and novel image reconstruction, neither additional delayed PET nor DTPI analyses improved the accuracy of PET-based LN staging. Dedicated visual assessment criteria performed very well. • DTPI did not improve accuracy of PET-based LN staging in NSCLC. • Analyzed SUV ratios were not superior to LN SUVmax or SUVmean. • A four-step visual score may allow highly accurate, standardized LN assessment.

Purpose To retrospectively assess the influence of the parameters of the body surface area (BSA) method in hepatic radioembolization using yttrium-90–labeled microspheres on the determination of the prescribed activity. Materials and Methods Data from 283 consecutive patients treated with radioembolization (BSA method) were included. For interindividual comparisons, activity concentrations (ACs; MBq/mL) were calculated for each liver. The impact of the BSA method parameters was assessed by analysis of variance and pairwise t test with Bonferroni-Holm correction. Results Prescribed activity was 1.01–2.71 GBq, with BSA, liver volume (LV), tumor burden, and the liver-lung shunt reduction factor (LLS RF) being significant contributing factors to the AC (all P P P Conclusions In the BSA model, BSA and LV showed only a moderate correlation, resulting in a significantly lower AC in patients with larger livers. Tumor burden percentage contributed little to the prescribed activity because the BSA model did not account for actual LVs and tumor volumes. These inaccuracies may potentially result in underdosage in patients with larger livers, especially if further LLS RF needs to be applied.

Rationale and Objectives The aim of the present study was to characterize the kinetics of two nanoparticle-based contrast agents for preclinical imaging, Exitron nano 6000 and Exitron nano 12000, and the iodinated agent eXIA 160 in both healthy mice and in a mouse model of hepatocellular carcinoma (HCC). Semiautomatic segmentation of liver lesions for estimation of total tumor load of the liver was evaluated in HCC mice. Materials and Methods The normal time course of contrast enhancement was assessed in 15 healthy C57BL/6 mice. Imaging of tumor spread in the liver was evaluated in 15 mice harboring a transgenic HCC model (ASV-B mice). Automatic segmentation of liver lesions for determination of total tumor burden of the liver was tested in three additional ASV-B mice before and after an experimental therapy. Results In healthy mice, clearance of the contrast agent from blood was completed within 3–4 hours for eXIA 160 and Exitron nano 6000, whereas complete blood clearance of Exitron nano 12000 required about 24 hours. eXIA 160 provided maximum liver contrast at 1 hour post injection (p.i.) followed by a continuous decline. Enhancement of liver contrast with Exitron nano 6000 and Exitron nano 12000 reached a plateau at about 4 hours p.i., which lasted until the end of the measurements at 96 hours p.i. Maximum contrast enhancement of the liver was not statistically different between Exitron nano 6000 and Exitron nano 12000, but was about three times lower for eXIA 160 (P Conclusions Both nanoparticle-based contrast agents provided stronger and longer lasting contrast enhancement of healthy liver parenchyma. Exitron nano 12000 allowed automatic segmentation of tumor lesions for estimation of the total tumor load in the liver.

Background. Fluorine-18 fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET) is a recommended standard in the staging and response assessment of 18F-FDG-avid lymphoma. Posttransplant lymphoproliferative disorder (PTLD) can be detected by 18F-FDG-PET at diagnosis with high sensitivity and specificity. However, the role of response assessment by end-of-treatment (EOT) PET has only been addressed in small case series. Methods. We performed a retrospective, multicenter study of 37 patients with CD20-positive PTLD after solid organ transplantation treated with uniform, up-to-date, first-line protocols in the prospective German PTLD registry who had received EOT 18F-FDG-PET between 2006 and 2014. Median follow-up was 5.0 years. Any nonphysiological 18F-FDG uptake (Deauville score greater 2) was interpreted as PET-positive. Results. By computed tomography (CT) final staging, 18 of 37 patients had a complete response, 18 had a partial response and 1 patient had stable disease. EOT PET was negative in 24 of 37 patients and positive in 13 of 37 patients. The positive predictive value of EOT PET for PTLD relapse was 38%, and the negative predictive value was 92%. Time to progression (TTP) and progression-free-survival were significantly longer in the PET negative group (P = 0.019 and P = 0.013). In the 18 patients in a partial response by CT staging, we noted highly significant differences in overall survival (P = 0.001), time to progression (P = 0.007), and progression-free survival (P < 0.001) by EOT PET. Conclusions. Even without baseline imaging, EOT PET in PTLD identifies patients at low risk of relapse and offers clinically relevant information, particularly in patients in a partial remission by CT staging.

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.