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This study explored factors that can predict effectiveness outcomes after transarterial radioembolization in colorectal liver metastases in the liver. In a cohort of 237 patients, among other factors, we found that an Aspartate transaminase to Platelet Ratio Index (APRI) value of > 0.40 was a particularly strong independent predictor of worse overall survival, progression-free survival and hepatic progression-free survival outcomes. Background: Transarterial radioembolisation (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with metastatic colorectal cancer in the liver (mCRC). A better understanding of the prognostic factors and treat-ment application can improve survival outcomes. Methods: We analysed the safety and effectiveness of 237 mCRC patients included in the prospective observational study CIRSE Registry for SIR-Spheres Therapy (CIRT) for indepen-dent prognostic factors for overall survival (OS), progression-free survival (PFS) and hepatic progression-free survival (hPFS) using the Cox proportional-hazard model. Results: The median OS was 9.8 months, median PFS was 3.4 months and median hPFS was 4.2 months. Independent prognostic factors for an improved overall survival were the absence of extra-hepatic disease ( P = .0391), prior locoregional procedures ( P = .0037), an Aspartate transaminase to Platelet Ratio Index (APRI) value of 0.40 ( P = .0416) and prior ablation ( P = .0323), and for hPFS these were 2 to 5 tumor nodules ( P = .0148), Albumin-bilirubin (ALBI) grade 3 ( P = .0075) and APRI > 0.40 ( P = .0207). During the study, 95 of 237 (40.1%) patients experienced 197 adverse events, with 28 of 237 (11.8%) patients having a grade 3 or higher adverse events. Conclusion: Including easy-to-acquire laboratory markers INR, APRI, ALBI and using partition model dosimetry can identify mCRC patients that may benefit from TARE.

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy is a validated treatment option for patients with advanced prostate cancer. Although PSMA expression is not limited to prostate tissue, little is known about its relevance to other types of cancer. Here, we present a case report of a patient with uterine leiomyosarcoma that is progressing while on immunotherapy and treated with177Lu-PSMA radionuclide therapy. We report for the first time that177Lu-PSMA radionuclide therapy combined with immunotherapy outside of prostate cancer. We did observe post-treatment reduction of tumor growth rate, although we did not notice disease response based on RECIST criteria. We suggest that177Lu-PSMA treatment especially combined with immunotherapy may be an option for patients with cancer without other therapeutic options. Insights:177Lu-PSMA radionuclide therapy should be considered for any tumor stained positive for PSMA.

Hepatocellular carcinoma (HCC) has the tendency to invade the portal and/or hepatic venous system. The invasion of the right atrium is uncommonly observed and constitutes a treatment challenge. We report the case of a patient with HCC invading the right atrium treated with 90Yttrium-transarterial radioembolization (90Y-TARE). Following the treatment, organizing pneumonia secondary to nivolumab occurred, raising the question of an interaction between 90Y-TARE and nivolumab. Electronic supplementary material The online version of this article (10.1007/s00270-020-02605-3) contains supplementary material, which is available to authorized users.

Introduction: Tumor growth rate (TGR), percentage of change in tumor volume/month, has been previously identified as an early radiological biomarker for treatment monitoring in neuroendocrine tumor (NET) patients. We assessed the performance and reproducibility of TGR at 3 months (TGR3m) as a predictor factor of progression-free survival (PFS), including the impact of imaging method and reader variability. Methods: Baseline and 3-month (±1 month) CT/MRI images from patients with advanced, grade 1–2 NETs were retrospectively reviewed by 2 readers. Influence of number of targets, tumor burden, and location of lesion on the performance of TGR3m to predict PFS was assessed by uni/multivariable Cox regression analysis. Agreement between readers was assessed by Lin’s concordance coefficient (LCC) and kappa coefficient (KC). Results: A total of 790 lesions were measured in 222 patients. Median PFS was 22.9 months. On univariable analysis, number of lesions (3m ≥0.8%/month (HR: 4.01 [95% CI: 2.31–6.97]), and watch and wait correlated with shorter PFS. No correlation was found between TGR3m and number of lesions (rho: −0.2; p value: 0.1930). No difference in mean TGR3m across organs was shown (p value: 0.6). Concordance between readers was acceptable (LCC: 0.52 [95% CI: 0.38–0.65]; KC: 0.57, agreement: 81.55%). TGR3m remained a significant prognostic factor when data from the second reader were employed (HR: 4.35 [95% CI: 2.44–7.79]; p value p value: 0.493). Discussion/Conclusion: TGR3m is a robust and early radiological biomarker able to predict PFS. It may be used to identify patients with advanced NETs who require closer radiological follow-up.

The University Hospital of Lausanne has heavily invested in the development of interdisciplinary oncology centers to improve the quality of care, and structure research and training. By integrating specialist nurses, it follows international recommendations. These specialists' nurses rephrase the information given by the doctor and ensure patients' understanding. They assess the patient's psychosocial situation and provides guidance if necessary. They support the patient in making informed choices about treatment and coping strategies. In addition to the outpatient clinics planned in accordance with the care pathway, she can be contacted between appointments to answer questions or concerns of any kind. This article shows the added value of these nurses in the care of oncology patients.Le CHUV s’est fortement investi dans le développement de centres interdisciplinaires en oncologie afin d’améliorer la qualité de la prise en charge, de structurer la recherche et la formation. En y intégrant des infirmières cliniciennes, il suit les recommandations internationales. Ces infirmières reprennent les informations données par le médecin et s’assurent de la compréhension du patient. Elles évaluent sa situation psychosociale et l’orientent au besoin. Elles soutiennent le patient dans ses choix de traitement ainsi que dans ses stratégies d’adaptation. Outre les entretiens planifiés en fonction du parcours de soins, elles sont joignables entre les rendez-vous pour répondre à des questions ou préoccupations de tout ordre. Cet article montre la plus-value que la présence de ces infirmières offre à la prise en charge des patients oncologiques.

The role of radioiodine treatment following total thyroidectomy for differentiated thyroid cancer is changing. The last major revision of the American Thyroid Association (ATA) Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer in 2015 changed treatment recommendations dramatically in comparison with the European Association of Nuclear Medicine (EANM) 2008 guidelines. We hypothesised that there is marked variability between the different treatment regimens used today.We analysed decision-making in all Swiss hospitals offering radioiodine treatment to map current practice within the community and identify consensus and discrepancies. RESULTS AND CONCLUSION: We demonstrated that for low-risk DTC patients after thyroidectomy, some institutions offered only follow-up, while RIT with significant activities is recommended in others. For intermediate- and high-risk patients, radioiodine treatment is generally recommended. Dosing and treatment preparation (recombinant human thyroid stimulation hormone (rhTSH) vs. thyroid hormone withdrawal (THW)) vary significantly among centres.

The rationale of this study was to investigate the performance of high-resolution CT (HRCT) versus 18 F-FDG PET/CT for the diagnosis of pulmonary lymphangitic carcinomatosis (PLC). Methods: In this retrospective institution-approved study, 94 patients addressed for initial staging of lung cancer with suspicion of PLC were included. Using double-blind analysis, we assessed the presence of signs favoring PLC on HRCT (smooth or nodular septal lines, subpleural nodularity, peribronchovascular thickening, satellite nodules, lymph node enlargement, and pleural effusion). 18 F-FDG PET/CT images were reviewed to qualitatively evaluate peritumoral uptake and to quantify tracer uptake in the tumoral and peritumoral areas. Histology performed on surgical specimens served as the gold standard for all patients. Results: Among 94 included patients, 73% (69/94) had histologically confirmed PLC. Peribronchovascular thickening, lymph node involvement, and increased peritumoral uptake were more often present in patients with PLC (P < 0.009). Metabolic variables, including tumor SUV max , SUV mean , metabolic tumor volume, and total lesion glycolysis, as well as peritumoral SUV max , SUV mean , and their respective ratios to background, were significantly higher in the PLC group than in the non-PLC group (P ≤ 0.0039). Sensitivity, specificity, and area under the receiver-operating-characteristic curve for peribronchovascular thickening (69%, 83%, and 0.76, respectively; 95% confidence interval [95%CI], 0.67-0.85) and increased peritumoral uptake (94%, 84%, and 0.89, respectively; 95%CI, 0.81-0.97) were similar (P = 0.054). For detecting PLC, sensitivity, specificity, and area under the receiver-operating-characteristic curve were significantly higher, at 97%, 92%, and 0.98, respectively (95%CI, 0.96-1.00), for peritumoral SUV max and 94%, 88%, and 0.96, respectively (95%CI, 0.92-1.00), for peritumoral SUV mean (all P ≤ 0.025). Conclusion: Qualitative evaluation of 18 F-FDG PET/CT and HRCT perform similarly for the diagnosis of PLC, with both being outperformed by 18 F-FDG PET/CT quantitative parameters.

Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes T-cell infiltration and enables responsiveness to combinatorial immunotherapy in an IFN-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity and depended on both cytotoxic CD4+ and CD8+ T cells. LDRT elicited predominantly CD4+ cells with features of exhausted effector cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, as well as a unique subset of activated dendritic cells expressing the NKG2D ligand RAE1. We translated these findings to a phase I clinical trial administering LDRT, low-dose cyclophosphamide, and immune checkpoint blockade to patients with immune-desert tumors. In responsive patients, the combinatorial treatment triggered T-cell infiltration, predominantly of CD4+ cells with Th1 signatures. Our data support the rational combination of LDRT with immunotherapy for effectively treating low T cell–infiltrated tumors.Significance:Low-dose radiation reprogrammed the tumor microenvironment of tumors with scarce immune infiltration and together with immunotherapy induced simultaneous mobilization of innate and adaptive immunity, predominantly CD4+ effector T cells, to achieve tumor control dependent on NKG2D. The combination induced important responses in patients with metastatic immune-cold tumors.This article is highlighted in the In This Issue feature, p. 1

Prophylactic cranial irradiation (PCI) in small-cell lung cancer (SCLC) patients improves survival. However, it is also associated with cognitive impairment, although the underlying mechanisms remain poorly understood. Our study aims to evaluate the impact of PCI and potential benefit of hippocampal sparing (HS) on brain metabolism assessed byWe retrospectively included 22 SCLC patients. 50% had hippocampal-sparing (HS) PCI.We found significant decreases inPCI induced a diffuse decrease in

Increasing knowledge regarding transarterial radioembolization (TARE) hepatic dose-response and dose-toxicity correlation is available but few studies have investigated dose-toxicity correlation in extra-hepatic tissues. We investigated absorbed dose levels for the appearance of focal lung damage in a case of off-target deposition of 90Y microspheres and compared them with the corresponding thresholds recommended to avoiding radiation induced lung injury following TARE.A 64-year-old male patient received 1.6 GBq of 90Y-labelled glass microspheres for an inoperable left lobe hepatocellular carcinoma. A focal off-target accumulation of radiolabeled microspheres was detected in the left lung upper lobe at the post-treatment 90Y-PET/CT, corresponding to a radiation-induced inflammatory lung lesion at the 3-months 18F-FDG PET/CT follow-up. 90Y-PET/CT data were used as input for Monte-Carlo based absorbed dose estimations. Dose-Volume-Histograms (DVH) were computed to characterize the heterogeneity of absorbed dose distribution. The dose level associated with the appearance of lung tissue damage was estimated as the median absorbed dose measured at the edge of the inflammatory nodule. To account for respiratory movements and possible inaccuracy of image co-registration, three different methods were evaluated to define the irradiated off-target volume.Monte Carlo-derived absorbed dose distribution showed a highly heterogeneous absorbed dose pattern at the site of incidental microsphere deposition (volume = 2.13 mL) with a maximum dose of 630 Gy. Absorbed dose levels ranging from 119 to 133 Gy, were estimated at the edge of the inflammatory nodule, depending on the procedure used to define the target volume.This report describes an original Monte Carlo based patient-specific dosimetry methodology for the study of the radiation-induced damage in a focal lung lesion after TARE. In our patient, radiation-induced focal lung damage occurred at significantly higher absorbed doses than those currently recommended for single administration or cumulative lung dose delivered during TARE.

Purpose Radioembolization has emerged as a treatment modality for patients with primary and secondary liver tumours. This observational study CIRT-FR (CIRSE Registry for SIR-Spheres Therapy in France) aims to evaluate real-life clinical practice on all patients treated with transarterial radioembolization (TARE) using SIR-Spheres yttrium-90 resin microspheres in France. In this interim analysis, safety and quality of life data are presented. Final results of the study, including secondary effectiveness outcomes, will be published later. Overall, CIRT-FR is aiming to support French authorities in the decision making on reimbursement considerations for this treatment. Methods Data on patients enrolled in CIRT-FR from August 2017 to October 2019 were analysed. The interim analysis describes clinical practice, baseline characteristics, safety (adverse events according to CTCTAE 4.03) and quality of life (according to EORTC QLQ C30 and HCC module) aspects after TARE. Results This cohort included 200 patients with hepatocellular carcinoma (114), metastatic colorectal cancer (mCRC; 38) and intrahepatic cholangiocarcinoma (33) amongst others (15). TARE was predominantly assigned as a palliative treatment (79%). 12% of patients experienced at least one adverse event in the 30 days following treatment; 30-day mortality was 1%. Overall, global health score remained stable between baseline (66.7%), treatment (62.5%) and the first follow-up (66.7%). Conclusion This interim analysis demonstrates that data regarding safety and quality of life generated by randomised-controlled trials is reflected when assessing the real-world application of TARE. Trial Registration Clinical Trials.gov NCT03256994.

Infectious endocarditis is a life-threatening disease, requiring prompt and accurate diagnosis. The aim of this article is to perform a systematic review and meta-analysis of the literature to estimate the performance of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) for the diagnosis of native valve endocarditis (NVE). Selected articles evaluating the diagnostic accuracy of 18 F-FDG PET/CT in patients with suspected NVE, resulting from a comprehensive literature search through the PubMed/MEDLINE and Cochrane library databases until April 2020, were included for the systematic review and meta-analysis. Seven studies (351 episodes of suspected NVE) were included. 18 F-FDG PET/CT yielded a pooled sensitivity of 36.3% and a pooled specificity of 99.1% for the diagnosis of NVE. The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 8.3, 0.6, and 15.3, respectively. The sensitivity increased using contemporary PET/CT device with state-of-the-art patient preparation as well as innovative image acquisitions or adding the results of 18 F-FDG PET/CT in a multimodality strategy. In our systematic review and meta-analysis, 18 F-FDG PET/CT yielded a poor pooled sensitivity with an otherwise excellent pooled specificity for the diagnosis of NVE; however, several factors may increase the sensitivity without affecting the specificity and these factors should be better evaluated in future studies.

The tumour endothelial marker 1 (TEM1/endosialin/CD248) is a receptor overexpressed in several human solid tumours and silenced in normal adult tissues, representing a suitable and potentially safe target for radioimmunotherapy of sarcoma. To develop new tools with improved TEM1 targeting properties, a new panel of antibody fragments was for the first time evaluated preclinically following 125I radiolabelling. The antibody fragment 1C1m-Fc, with the highest human/murine TEM1 binding affinity, was extensively characterized in vitro and in vivo in a Ewing's sarcoma human xenograft mouse model. In silico studies were also performed to elucidate the influence of a single amino acid mutation in the complementarity-determining region (CDR3) of the heavy chain, upon affinity maturation of the parental clone 1C1-Fc. From this study, 1C1m-Fc emerged as a promising candidate for the development of TEM1-targeted radioimmunoconjugates, namely to be further explored for theranostic applications with other suitable medical radionuclides.

Endosialin/tumor endothelial marker-1 (TEM1) is an attractive theranostic target expressed by the microenvironment of a wide range of tumors, as well as by sarcoma and neuroblastoma cells. We report on the radiolabeling and preclinical evaluation of the scFv78-Fc, a fully human TEM1-targeting antibody fragment cross-reactive with mouse TEM1.The scFv78-Fc was conjugated with the chelator p-SCN-Bn-CHX-A"-DTPA, followed by labeling with indium-111. The number of chelators per molecule was estimated by mass spectrometry. A conventional saturation assay, extrapolated to infinite antigen concentration, was used to determine the immunoreactive fraction of the radioimmunoconjugate. The radiopharmaceutical biodistribution was assessed in immunodeficient mice grafted with Ewing's sarcoma RD-ES and neuroblastoma SK-N-AS human TEM1-positive tumors. The full biodistribution studies were preceded by a dose-escalation experiment based on the simultaneous administration of the radiopharmaceutical with increasing amounts of unlabeled scFv78-Fc. Radiation dosimetry extrapolations to human adults were obtained from mouse biodistribution data according to established methodologies and additional assumptions concerning the impact of the tumor antigenic sink in the cross-species translation.[[

Purpose Bone scintigraphy with 99mTc-labeled diphosphonates can identify prostate cancer bone metastases with high sensitivity, but relatively low specificity, because benign conditions such as osteoarthritis can also trigger osteoblastic reactions. We aimed to investigate the diagnostic performance of 99mTc-2,3-dicarboxy propane-1,1-diphosphonate (99mTc-DPD) uptake quantification by single-photon emission computed tomography coupled with computed tomography (SPECT/CT) for distinguishing prostate cancer bone metastases from spinal and pelvic osteoarthritic lesions. Methods We retrospectively assessed 26 bone scans from 26 patients with known prostate cancer bone metastases and 13 control patients with benign spinal and pelvic osteoarthritic changes without known neoplastic disease. Quantitative SPECT/CT (xSPECT, Siemens Symbia Intevo, Erlangen, Germany) was performed and standardized uptake values (SUVs) were quantified with measurements of SUVmax and SUVmean (g/mL) in all bone metastases for the prostate cancer group and in spinal and pelvic osteoarthritic changes for the control group. We used receiver operating characteristics (ROC) curves to determine the optimum SUVmax cutoff value to distinguish between bone metastases and benign spinal and pelvic lesions. Results In total, 264 prostate cancer bone metastases were analyzed, showing a mean SUVmax and SUVmean of 34.6 ± 24.6 and 20.8 ± 14.7 g/mL, respectively. In 24 spinal and pelvic osteoarthritic lesions, mean SUVmax and SUVmean were 14.2 ± 3.8 and 8.9 ± 2.2 g/mL, respectively. SUVmax and SUVmean were both significantly different between the bone metastases and osteoarthritic groups (p ≤ 0.0001). Using a SUVmax cutoff of 19.5 g/mL for prostate cancer bone metastases in the spine and pelvis, sensitivity, specificity, positive and negative predictive values were 87, 92, 99 and 49%, respectively. Conclusion This study showed significant differences in quantitative 99mTc-DPD uptake on bone SPECT/CT between prostate cancer bone metastases and spinal and pelvic osteoarthritic changes, with higher SUVmax and SUVmean in metastases. Using a SUVmax cutoff of 19.5 g/mL, high specificity and positive predictive value for metastases identification in the spine and pelvis were found, thus increasing accuracy of bone scintigraphy.

We present images of a 50-year-old man who referred for treatment of a classic Hodgkin lymphoma. While F-FDG PET/CT demonstrated a complete metabolic remission after chemotherapy, an increased F-FDG uptake of a right testicular lesion in F-FDG PET/CT and an unexplained bilateral gynecomastia were observed. A benign Leydig cell tumor was histopathologically proved after a right radical orchiectomy. The serum estradiol level was abnormally elevated reflecting the estrogen-secreting profile. This report highlights that a focal F-FDG uptake in the testicular region with unexplained gynecomastia should suggest the diagnosis of an estrogen-secreting Leydig cell tumor on F-FDG PET/CT.

Nuclear medicine diagnostics, therapy and theranostics in the context of modern oncology

On conventional PET/CT, and under physiological conditions, the volume of the pituitary gland (PG) is small, and its metabolic activity is commonly comparable to the surrounding background level in 18F-FDG imaging. We compared the physiological 18F-FDG uptake of the PG in patients imaged with digital PET (dPET) and with conventional PET (cPET). Additionally, we performed phantom experiments to characterize signal recovery and detectability of small structures. We retrospectively included 10 dPET and 10 cPET patients and measured PG SUVmax, SUVmean and SUVratio (using cerebellum as reference). We imaged a modified NEMA/IEC phantom with both dPET and cPET (background activity 5 kBq/mL, and 3× and 5× higher concentrations in ∅2–20-mm spherical inserts). Mean recovery coefficients (RCmean) and signal-difference-to-noise-ratio (SDNR) were computed to assess lesion detectability. Patients imaged with dPET presented higher PG SUVmax and SUVratio (SUVR) compared to patients imaged with cPET (4.7 ± 2.05 vs. 2.9 ± 0.64, p = 0.004; and 0.62 ± 0.25 vs 0.39 ± 0.09, p = 0.029, respectively), while there was no difference for SUVmean (2.7 ± 1.32 vs 2.1 ± 0.44, p = 0.39). Thus, with a SUV readout scale of 0–5 g/mL, normal PG appeared abnormally hot with dPET, but not with cPET. Phantom evidenced higher RCmean in dPET compared to cPET. For both 3x and 5x measurements, lesion detectability according to size was systematically superior with dPET. In conclusion, patients imaged with dPET presented higher 18F-FDG physiological uptake of the PG as compared to patients imaged with cPET. These findings were supported by phantom experiments demonstrating superior signal recovery and small region detectability with dPET. Awareness of this new “higher” SUV of the normal 18F-FDG uptake of the PG is important to avoid potential pitfalls in image interpretation, notably in oncologic patients treated with immunotherapy, who are at increased risk to develop hypophysitis.

Survival of patients with uveal melanoma metastatic to the liver correlates strongly with disease control in the liver. Unfortunately, there are no standardized treatments for this chemoresistant disease. Selective internal radiation therapy (SIRT) has been tested as salvage therapy, but no data exist about its use as first-line therapy. The purpose of this study was to investigate the safety and efficacy of SIRT as first-line therapy in patients with uveal melanoma metastatic to the liver. Methods: This retrospective analysis of a prospectively collected cohort included 22 patients treated with first-line SIRT. Biochemical and clinical toxicities were recorded. Tumor response was determined according to the European Association for the Study of Liver Disease (EASL) criteria. Predictive factors of survival were analyzed by univariate and multivariate analysis. Overall survival was calculated using the Kaplan–Meier method with the log-rank test. Results: Grade 3–4 biologic and clinical toxicities occurred in 24% of patients (for both). According to the EASL criteria, disease control at 6 mo after SIRT was achieved in 15 (52%) of the 29 SIRT patients and was predictive of survival. Median overall survival from the first SIRT was 18 mo (95% confidence interval [95%CI], 8–28 mo). At the time of the analysis, 5 patients (23%) were still alive. In multivariate analysis, largest lesion size (hazard ratio [HR], 1.22; 95%CI, 0.98–1.53], liver tumor volume (HR, 1.002; 95%CI, 1.0004–1.003), subsequent systemic therapy (HR, 0.04; 95%CI, 0.006–0.24), and liver-directed locoregional therapy (HR, 0.204; 95%CI, 0.04–0.94) were predictive of survival. Conclusion: First-line SIRT is safe and produced promising outcomes in patients with uveal melanoma metastatic to the liver. Subsequent systemic and liver-directed locoregional therapies ameliorated survival, highlighting the potential for improved outcomes with combination approaches. The results of this study suggest that prospective trials using first-line SIRT should be considered.

Introduction Tumor growth rate (TGR; percent size change per month [%/m]) is postulated to be an early radiological biomarker to overcome limitations of RECIST. This study aimed to assess the impact of TGR in neuroendocrine tumors (NETs) and potential clinical and therapeutic applications. Materials and Methods Patients (pts) with advanced grade (G) 1/2 NETs from the pancreas or small bowel initiating systemic treatment (ST) or watch and wait (WW) were eligible. Baseline and follow-up scans were retrospectively reviewed to calculate TGR at pretreatment (TGR0), first follow-up (TGRfirst), and 3(±1) months of study entry (TGR3m). Results Out of 905 pts screened, 222 were eligible. Best TGRfirst (222 pts) cutoff was 0.8 (area under the curve, 0.74). When applied to TGR3m (103 pts), pts with TGR3m Conclusion TGR is an early radiological biomarker able to predict PFS and to identify patients with advanced NETs who may require closer radiological follow-up. Implications for Practice Tumor growth rate at 3 months (TGR3m) is an early radiological biomarker able to predict progression-free survival and to identify patients with advanced neuroendocrine tumors who may require closer radiological follow-up. It is feasible to calculate TGR3m in clinical practice and it could be a useful tool for guiding patient management. This biomarker could also be implemented in future clinical trials to assess response to therapy.

This is the first described case of effective and durable cytoreduction after PRRT with

Transarterial radioembolization (TARE) with 90Y-loaded microspheres is an established therapeutic option for inoperable hepatic tumors. Increasing knowledge regarding TARE hepatic dose-response and dose-toxicity correlation is available but few studies have investigated dose-toxicity correlation in extra-hepatic tissues. We investigated absorbed dose levels for the appearance of focal lung damage in a case of off-target deposition of 90Y microspheres and compared them with the corresponding thresholds recommended to avoiding radiation induced lung injury following TARE. A 64-year-old male patient received 1.6 GBq of 90Y-labelled glass microspheres for an inoperable left lobe hepatocellular carcinoma. A focal off-target accumulation of radiolabeled microspheres was detected in the left lung upper lobe at the post-treatment 90Y-PET/CT, corresponding to a radiation-induced inflammatory lung lesion at the 3-months 18F-FDG PET/CT follow-up. 90Y-PET/CT data were used as input for Monte-Carlo based absorbed dose estimations. Dose-volume-histograms were computed to characterize the heterogeneity of absorbed dose distribution. The dose level associated with the appearance of lung tissue damage was estimated as the median absorbed dose measured at the edge of the inflammatory nodule. To account for respiratory movements and possible inaccuracy of image co-registration, three different methods were evaluated to define the irradiated off-target volume. Monte Carlo-derived absorbed dose distribution showed a highly heterogeneous absorbed dose pattern at the site of incidental microsphere deposition (volume = 2.13 ml) with a maximum dose of 630 Gy. Absorbed dose levels ranging from 119 Gy to 133 Gy, were estimated at the edge of the inflammatory nodule, depending on the procedure used to define the target volume. This report describes an original Monte Carlo based patient-specific dosimetry methodology for the study of the radiation-induced damage in a focal lung lesion after TARE. In our patient, radiation-induced focal lung damage occurred at significantly higher absorbed doses than those considered for single administration or cumulative lung dose delivered during TARE.

Purpose: To evaluate the diagnostic impact and clinical significance of FDG-avid bone lesions detected by FDG-PET/CT in patients with lymphoma. Methods: The study population comprised 50 consecutive patients (mean age 41.7±15.5years; 27 female, 23 male; 41 staging, 9 restaging) with Hodgkin's disease (n=22) or aggressive non-Hodgkin's lymphoma (n=28) in whom FDG-avid bone lesions were detected by FDG-PET/CT. All patients had either direct biopsy of the FDG-avid bone lesion (n=18), standard bone marrow biopsy at the iliac crest (BMB; n=43) or both procedures (n=11). In 15 patients, additional MRI of the bone lesions was performed. All patients underwent FDG-PET/CT after the end of treatment. All CT images of FDG-PET/CT scans were analysed independently regarding morphological osseous changes and compared with FDG-PET results. Results: In the 50 patients, 193 FDG-avid lesions were found by PET/CT. The mean standardised uptake value was 6.26 (±3.22). All direct bone biopsies (n=18) of the FDG-avid lesions proved the presence of lymphomatous infiltration. BMB (n=43) was positive in 12 patients (27.9%). In CT, 32 of 193 (16.6%) lesions were detected without the PET information. No additional morphological bone infiltration was detected on CT compared with FDG-PET. All morphological bone alterations on CT scans persisted after the end of therapy. Additional PET/CT information regarding uni- or multifocal bone involvement resulted in lymphoma upstaging in 21 (42%) patients compared with the combined information provided by CT and BMB. Conclusion: In patients with FDG-avid bone lesions, FDG-PET is superior to CT alone or in combination with unilateral BMB in detecting bone marrow involvement, leading to upstaging in a relevant proportion of patients

International audience; IntroductionAim was to develop a full automatic clustering approach of the time-activity curves (TAC) from dynamic 18F-FET PET and evaluate its association with IDH1 mutation status and survival in patients with gliomas.MethodsThirty-seven patients (mean age: 45±13 y) with newly diagnosed gliomas and dynamic 18F-FET PET before any histopathologic investigation or treatment were retrospectively included. Each dynamic 18F-FET PET was realigned to the first image and spatially normalized in the Montreal Neurological Institute template. A tumor mask was semi-automatically generated from Z-score maps. Each brain tumor voxel was clustered in one of the 3 following centroids using dynamic time warping and k-means clustering (centroid #1: slowly increasing slope; centroid #2: rapidly increasing followed by slowly decreasing slope; and centroid #3: rapidly increasing followed by rapidly decreasing slope). The percentage of each dynamic 18F-FET TAC within tumors and other conventional 18F-FET PET parameters (maximum and mean tumor-to-brain ratios [TBRmax and TBRmean], time-to-peak [TTP] and slope) was compared between wild-type and IDH1 mutant tumors. Their prognostic value was assessed in terms of progression free-survival (PFS) and overall survival (OS) by Kaplan-Meier estimates.ResultsTwenty patients were IDH1 wild-type and 17 IDH1 mutant. Higher percentage of centroid #1 and centroid #3 within tumors were positively (P = 0.016) and negatively (P = 0.01) correlated with IDH1 mutated status. Also, TBRmax, TBRmean, TTP, and slope discriminated significantly between tumors with and without IDH1 mutation (P range 0.01 to 0.04). Progression occurred in 22 patients (59%) at a median of 13.1 months (7.6–37.6 months) and 13 patients (35%) died from tumor progression. Patients with a percentage of centroid #1 > 90% had a longer survival compared with those with a percentage of centroid #1 < 90% (P = 0.003 for PFS and P = 0.028 for OS). This remained significant after stratification on IDH1 mutation status (P = 0.029 for PFS and P = 0.034 for OS). Compared to other conventional 18F-FET PET parameters, TTP and slope were associated with PFS and OS (P range 0.009 to 0.04).ConclusionsBased on dynamic 18F-FET PET acquisition, we developed a full automatic clustering approach of TAC which appears to be a valuable noninvasive diagnostic and prognostic marker in patients with gliomas.

(D)-F-18-fluoromethyltyrosine (D-F-18-FMT), or BAY 86-9596, is a novel F-18-labeled tyrosine derivative rapidly transported by the L-amino acid transporter (LAT-1), with a faster blood pool clearance than the corresponding L-isomer. The aim of this study was to demonstrate the feasibility of tumor detection in patients with non-small cell lung cancer (NSCLC) or head and neck squamous cell cancer (HNSCC) compared with inflammatory and physiologic tissues in direct comparison to F-18-FDG. Methods: 18 patients with biopsy-proven NSCLC (n = 10) or HNSCC (n = 8) were included in this Institutional Review Board-approved, prospective multicenter study. All patients underwent F-18-FDG PET/CT scans within 21 d before D-F-18-FMT PET/CT. For all patients, safety and outcome data were assessed. Results: No adverse reactions were observed related to D-F-18-FMT. Fifty-two lesions were F-18-FDG-positive, and 42 of those were malignant (34 histologically proven and 8 with clinical reference). Thirty-two of the 42 malignant lesions were also D-F-18-FMT-positive, and 10 lesions had no tracer uptake above the level of the blood pool. Overall there were 34 true-positive, 8 true-negative, 10 false-negative, and only 2 false-positive lesions for D-F-18-FMT, whereas F-18-FDG was true-positive in 42 lesions, with 10 false-positive and only 2 false-negative, resulting in a lesion-based detection rate for D-F-18-FMT and F-18-FDG of 77% and 95%, respectively, with an accuracy of 78% for both tracers. A high D-F-18-FMT tumor-to-blood pool ratio had a negative correlation with overall survival (P = 0.050), whereas the F-18-FDG tumor-to-blood pool ratio did not correlate with overall survival. Conclusion: D-F-18-FMT imaging in patients with NSCLC and HNSCC is safe and feasible. The presented preliminary results suggest a lower sensitivity but higher specificity for D-F-18-FMT over F-18-FDG, since there is no D-F-18-FMT uptake in inflammation. This increased specificity may be particularly beneficial in areas with endemic granulomatous disease and may improve clinical management. Further clinical investigations are needed to determine its clinical value and relevance for the prediction of survival prognosis.

PURPOSE: The purpose of this study was to evaluate prospectively, in patients with liver metastases, the ability of computed tomographic (CT) perfusion to predict the morphologic response and survival after transarterial radioembolization (TARE). METHODS: Thirty-eight patients (22 men; mean [SD] age, 63 [12] years) with otherwise therapy-refractory liver metastases underwent dynamic, contrast-enhanced CT perfusion within 1 hour before treatment planning catheter angiography, for calculation of the arterial perfusion (AP) of liver metastases, 20 days before TARE with Yttrium-90 microspheres. Treatment response was evaluated morphologically on follow-up imaging (mean, 114 days) on the basis of the Response Evaluation Criteria in Solid Tumors criteria (version 1.1). Pretreatment CT perfusion was compared between responders and nonresponders. One-year survival was calculated including all 38 patients using the Kaplan-Meier curves; the Cox proportional hazard model was used for calculating predictors of survival. RESULTS: Follow-up imaging was not available in 11 patients because of rapidly deteriorating health or death. From the remaining 27, a total of 9 patients (33%) were classified as responders and 18 patients (67%) were classified as nonresponders. A significant difference in AP was found on pretreatment CT perfusion between the responders and the nonresponders to the TARE (P < 0.001). Change in tumor size on the follow-up imaging correlated significantly and negatively with AP before the TARE (r = -0.60; P = 0.001). Receiver operating characteristics analysis of AP in relation to treatment response revealed an area under the curve of 0.969 (95% confidence interval, 0.911-1.000; P < 0.001). A cutoff AP of 16 mL per 100 mL/min was associated with a sensitivity of 100% (9/9) (95% CI, 70%-100%) and a specificity of 89% (16/18) (95% CI, 62%-96%) for predicting therapy response. A significantly higher 1-year survival after the TARE was found in the patients with a pretreatment AP of 16 mL per 100 mL/min or greater (P = 0.028), being a significant, independent predictor of survival (hazard ratio, 0.101; P = 0.015). CONCLUSIONS: Arterial perfusion of liver metastases, as determined by pretreatment CT perfusion imaging, enables prediction of short-term morphologic response and 1-year survival to TARE.

The aim of this study was to compare survival of patients treated for unresectable hepatocellular carcinoma (uHCC) with

Early diagnosis of cardiac sarcoidosis remains difficult in the absence of specific symptoms. The evolution and prognosis of the disease are strongly correlated to an early and appropriate treatment. The multi-modality assessment based on cardiac MRI and positron emission tomography associated with computed tomography (PET/CT) has significantly improved the detection of cardiac sarcoidosis over the last two decades. These approaches appear as useful and suitable imaging strategy for the early diagnosis, the assessment of the disease extent as well as the management and therapeutic follow-up. This article is a didactic review on cardiac sarcoidosis, with a special focus on recent diagnostic and therapeutic modalities, prognosis and interest of imaging techniques.

Purpose: To investigate the clinical value of 18F-fluorocholine PET/CT (CH-PET/CT) in treatment decisions in patients with recurrent prostate cancer (rPCA). Methods: The study was a retrospective evaluation of 156 patients with rPCA and CH-PET/CT for restaging. Questionnaires for each examination were sent to the referring physicians 14-64months after examination. Questions included information regarding initial extent of disease, curative first-line treatment, and the treatment plan before and after CH-PET/CT. Additionally, PSA values at diagnosis, after initial treatment, before CH-PET/CT and at the end of follow-up were also obtained from the questionnaires. Results: Mean follow-up was 42months. The mean Gleason score was 6.9 at initial diagnosis. Initial treatment was: radical prostatectomy in 110 patients, radiotherapy in 39, and combined prostatectomy and radiotherapy in 7. Median PSA values before CH-PET/CT and at the end of follow-up were 3.40ng/ml and 0.91ng/ml. PSA levels remained stable, decreased or were below measurable levels in 108 patients. PSA levels increased in 48 patients. In 75 of the 156 patients (48%) the treatment plan was changed due to the CH-PET/CT findings. In 33 patients the therapeutic plan was changed from palliative treatment to treatment with curative intent. In 15 patients treatment was changed from curative to palliative. In 8 patients treatment was changed from curative to another strategy and in 2 patients from one palliative strategy to another. In 17 patients the treatment plan was adapted. Conclusion: CH-PET/CT has an important impact on the therapeutic strategy in patients with rPCA and can help to determine an appropriate treatment

Purpose To prospectively analyze different FDG-PET/CT-parameters (modified RECIST, SUVmax, TLG, PETvol) in patients with malignant pleural mesothelioma (MPM) under continued pemetrexed and platin based treatment. Methods Patients with biopsy proven MPM undergoing treatment with pemetrexed and platin based treatment were prospectively included in the study. Integrated FDG-PET/CT imaging was performed within 2 weeks before therapy and after every three consecutive cycles of combined chemotherapy. All CT-images were evaluated according to the modified RECIST (modRECIST) criteria. All FDG-PET/CT images were analyzed using SUVmax (maximum Standard Uptake Value) according to the EORTC criteria, change in Total Lesion Glycolysis (TLG) and FDG volume (PETvol). Percent change in all parameters compared to the initial, pre-therapeutic and the previous FDG–PET/CT scan. ModRECIST, EORTC guidelines, increase or decrease in TLG and PETvol was correlated with overall survival (OS) using the Log Rank Test. Results 41 patients with MPM were prospectively included in this study. The median OS of the study population is 439 days (111–1128). 41 patients had initial staging, 41 patients completed 3 cycles, 28 patients completed 6 cycles, 19 patients completed 9 cycles, 11 patients completed 12 cycles, 5 patients completed 15 cycles, 4 patients completed 18 cycles and 1 patient completed 21 cycles of chemotherapy. Chemotherapy was well tolerated up to 21 cycles. SUVmax showed a high variance over time for individual patients and change in SUVmax using EORTC guidelines did not predict OS at any time point. Ongoing morphological response in CT using modRECIST had highest correlation with OS and predicted survival up to the 15th cycle of continued permetrexed and platin based treatment. The correlations of response of the volume based PET parameters (TLG and PETvol) and OS are inferior to the morphological modRECIST parameter. Conclusion Permetrexed and platin based treatment in MPM patients can be given over a prolonged time with good tolerance. Therapy response should be assessed by modRECIST in CT but not with SUVmax in FDG-PET. Long term permetrexed and platin therapy should be considered in MPM patients with good tolerance of treatment and ongoing morphological response in CT.

Background: Use of FDG-PET/CT for staging and restaging of lymphoma patients is widely incorporated into current practice guidelines. Our aim was to prospectively evaluate the diagnostic performance of FDG-PET/MRI and WB-DW-MRI compared with FDG-FDG-PET/CT using a tri-modality PET/CT-MRI system. Methods: From 04/12 to 01/14, a total of 82 FDG-PET/CT examinations including an additional scientific MRI on a tri-modality setup were performed in 61 patients. FDG-PET/CT, FDG-PET/MRI, and WB-DW-MRI were independently analyzed. A lesion with a mean ADC below a threshold of 1.2 x 10\(^{-3}\) mm\(^2\)/s was defined as positive for restricted diffusion. FDG-PET/CT and FDG-PET/MRI were evaluated for the detection of lesions corresponding to lymphoma manifestations according to the German Hodgkin Study Group. Imaging findings were validated by biopsy (n = 21), by follow-up imaging comprising CT, FDG-PET/CT, and/or FDG-PET/MRI (n = 32), or clinically (n = 25) (mean follow-up: 9.1 months). Results: FDG-PET/MRI and FDG-PET/CT accurately detected 188 lesions in 27 patients. Another 54 examinations in 35 patients were negative. WB-DW-MRI detected 524 lesions, of which 125 (66.5 % of the aforementioned 188 lesions) were true positive. Among the 188 lesions positive for lymphoma, FDG-PET/MRI detected all 170 instances of nodal disease and also all 18 extranodal lymphoma manifestations; by comparison, WB-DW-MRI characterized 115 (67.6 %) and 10 (55.6 %) lesions as positive for nodal and extranodal disease, respectively. FDG-PET/MRI was superior to WB-DW-MRI in detecting lymphoma manifestations in patients included for staging (113 vs. 73), for restaging (75 vs. 52), for evaluation of high-(127 vs. 81) and low-grade lymphomas (61 vs. 46), and for definition of Ann Arbor stage (WB-DW-MRI resulted in upstaging in 60 cases, including 45 patients free of disease, and downstaging in 4). Conclusion: Our results indicate that FDG-PET/CT and FDG-PET/MRI probably have a similar performance in the clinical work-up of lymphomas. The performance of WB-DW-MRI was generally inferior to that of both FDG-PET-based methods but the technique might be used in specific scenarios, e.g., in low-grade lymphomas and during surveillance.

Introduction Amino-acids positron emission tomography (PET) is increasingly used in the diagnostic workup of patients with gliomas, including differential diagnosis, evaluation of tumor extension, treatment planning and follow-up. Recently, progresses of computer vision and machine learning have been translated for medical imaging. Aim was to demonstrate the feasibility of an automated 18F-fluoro-ethyl-tyrosine (18F-FET) PET lesion detection and segmentation relying on a full 3D U-Net Convolutional Neural Network (CNN). Methods All dynamic 18F-FET PET brain image volumes were temporally realigned to the first dynamic acquisition, coregistered and spatially normalized onto the Montreal Neurological Institute template. Ground truth segmentations were obtained using manual delineation and thresholding (1.3 x background). The volumetric CNN was implemented based on a modified Keras implementation of a U-Net library with 3 layers for the encoding and decoding paths. Dice similarity coefficient (DSC) was used as an accuracy measure of segmentation. Results Thirty-seven patients were included (26 [70%] in the training set and 11 [30%] in the validation set). All 11 lesions were accurately detected with no false positive, resulting in a sensitivity and a specificity for the detection at the tumor level of 100%. After 150 epochs, DSC reached 0.7924 in the training set and 0.7911 in the validation set. After morphological dilatation and fixed thresholding of the predicted U-Net mask a substantial improvement of the DSC to 0.8231 (+ 4.1%) was noted. At the voxel level, this segmentation led to a 0.88 sensitivity [95% CI, 87.1 to, 88.2%] a 0.99 specificity [99.9 to 99.9%], a 0.78 positive predictive value: [76.9 to 78.3%], and a 0.99 negative predictive value [99.9 to 99.9%]. Conclusions With relatively high performance, it was proposed the first full 3D automated procedure for segmentation of 18F-FET PET brain images of patients with different gliomas using a U-Net CNN architecture.

BACKGROUND DOTATATE-based radionuclides have added new options in the diagnosis and treatment of meningiomas; however, a reliable predictor of tumor growth has still not been established. METHODS We analyzed 64 meningiomas imaged with (68)Ga-DOTATATE PET. Tumor growth rates were calculated by volumetric analysis of sequential MRI scans. Maximums of standardized uptake values (SUVmax) were correlated with tumor growth and covariates. RESULTS World Health Organization (WHO) grades I and II meningiomas showed a correlation of SUVmax and tumor growth rate (meningiomas limited to the intracranial compartment: r = 0.757, P < .001, and transosseous growing meningiomas: r = 0.819, P = .024). SUVmax was significantly higher and the slope of the linear regression significantly steeper in transosseous compared with intracranial meningiomas (both P < .001). The association remained significant in multivariate analysis, and the prediction of tumor growth rate was independent of WHO grade. Anaplastic meningiomas showed no significant correlation of SUVmax and tumor growth. CONCLUSIONS (68)Ga-DOTATATE PET is a reliable predictor of tumor growth in WHO grades I and II meningiomas and provides additional information to conventional cross-sectional imaging modalities. Hence, (68)Ga-DOTATATE PET can assist in selecting the time point for treatment initiation. Furthermore, meningiomas with fast tumor growth and transosseous expansion elicit the highest DOTATATE binding; therefore, they might be especially suited for DOTATATE-based therapy.

To evaluate in patients with hepatocellular carcinoma (HCC), whether assessment of tumor heterogeneity by histogram analysis of computed tomography (CT) perfusion helps predicting response to transarterial radioembolization (TARE).Sixteen patients (15 male; mean age 65 years; age range 47-80 years) with HCC underwent CT liver perfusion for treatment planning prior to TARE with Yttrium-90 microspheres. Arterial perfusion (AP) derived from CT perfusion was measured in the entire tumor volume, and heterogeneity was analyzed voxel-wise by histogram analysis. Response to TARE was evaluated on follow-up imaging (median follow-up, 129 days) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results of histogram analysis and mean AP values of the tumor were compared between responders and non-responders. Receiver operating characteristics were calculated to determine the parameters' ability to discriminate responders from non-responders.According to mRECIST, 8 patients (50%) were responders and 8 (50%) non-responders. Comparing responders and non-responders, the 50th and 75th percentile of AP derived from histogram analysis was significantly different [AP 43.8/54.3 vs. 27.6/34.3 mL min(-1) 100 mL(-1)); p0.05], while the mean AP of HCCs (43.5 vs. 27.9 mL min(-1) 100 mL(-1); p0.05) was not. Further heterogeneity parameters from histogram analysis (skewness, coefficient of variation, and 25th percentile) did not differ between responders and non-responders (p0.05). If the cut-off for the 75th percentile was set to an AP of 37.5 mL min(-1) 100 mL(-1), therapy response could be predicted with a sensitivity of 88% (7/8) and specificity of 75% (6/8).Voxel-wise histogram analysis of pretreatment CT perfusion indicating tumor heterogeneity of HCC improves the pretreatment prediction of response to TARE.

372 Objectives To evaluate a noninvasive whole-body parametric image generation technique with high resolution PET-CT. Methods Patlak plot and a linear regression with spatial constraint (LRSC) algorithm was used to generate parametric images of FDG influx rate constant Ki and distribution volume V. Fifteen single-direction dynamic multi-bed (7 beds/pass) passes were performed after initial 6-min single-bed dynamic scan (with heart centered in the field of view), with 45 sec/bed as implemented on the Siemens mCT scanner. PET images were reconstructed with time of flight and spatial resolution modeling. Aorta time activity curve (TAC) was obtained for image derived input function. 8-10 venous blood samples were obtained over total 90-min scan. This is an ongoing project and 5 patients studies were collected. SUV images calculated from 70 to 90 min post FDG injection were used for comparison. Results Using a single blood sampling at ~40 min to scale aorta TAC showed lowest variation in the ratio of aorta TACs to FDG blood activities. It was visually identified that Ki and V images appears to be improved by using the advanced mCT scanner, as compared to our previous studies. Compared to the delayed SUV images, the higher contrast Ki images improved visual detection of tumor lesions within tissues of high back ground FDG activity. The V images provided a quantitative measurements on blood volume and vascular density and function which is an important biomarker in monitoring tumor response to treatment. Conclusions The whole-body parametric images of Ki and V generated from dynamic multi-bed FDG data by using mCT scanner and robust LRSC algorithm provided multi-functional information of normal and abnormal tissues, and higher contrast in tumor to background than SUV images . The clinical values of both Ki and V parametric images are under investigation.

Targeting cancer cells with vitamin B12 (cobalamin) is hampered by unwanted physiologic tissue uptake mediated by transcobalamin. Adhering to good manufacturing practice, we have developed a new (99m)Tc-cobalamin derivative ((99m)Tc(CO)3-[(4-amido-butyl)-pyridin-2-yl-methyl-amino-acetato] cobalamin, (99m)Tc-PAMA-cobalamin). The derivative shows no binding to transcobalamin but is recognized by haptocorrin, a protein present in the circulation and notably expressed in many tumor cells. In this prospective study, we investigated cancer-specific uptake of (99m)Tc-PAMA-cobalamin in 10 patients with various metastatic tumors. METHODS: Ten patients with biopsy-proven metastatic cancer were included. Dynamic imaging was started immediately after injection of 300-500 MBq of (99m)Tc-PAMA-cobalamin, and whole-body scintigrams were obtained at 10, 30, 60, 120, and 240 min and after 24 h. The relative tumor activity using SPECT/CT over the tumor region after 4 h was measured in comparison to disease-free lung parenchyma. Patients 3-10 received between 20 and 1,000 μg of cobalamin intravenously before injection of (99m)Tc-PAMA-cobalamin. The study population comprised 4 patients with adenocarcinomas of the lung, 3 with squamous cell carcinomas of the hypopharyngeal region, 1 with prostate adenocarcinoma, 1 with breast, and 1 with colon adenocarcinoma. RESULTS: The median age of the study group was 61 ± 11 y. Six of 10 patients showed positive tumor uptake on (99m)Tc-PAMA-cobalamin whole-body scintigraphy. The scan was positive in 1 patient with colon adenocarcinoma, in 3 of 4 lung adenocarcinomas, in 1 of 3 hypopharyngeal squamous cell carcinomas, and in 1 breast adenocarcinoma. Renal uptake was between 1% and 3% for the left kidney. Predosing with cobalamin increased the tumor uptake and improved blood-pool clearance. The best image quality was achieved with a predose of 20-100 ug of cold cobalamin. The mean patient dose was 2.7 ± 0.9 mSv/patient. CONCLUSION: To our knowledge, we report for the first time on (99m)Tc-PAMA-cobalamin imaging in patients with metastatic cancer disease and show that tumor targeting is feasible. Targeting cancer cells with vitamin B12 (cobalamin) is hampered by unwanted physiologic tissue uptake mediated by transcobalamin. Adhering to good manufacturing practice, we have developed a new (99m)Tc-cobalamin derivative ((99m)Tc(CO)3-[(4-amido-butyl)-pyridin-2-yl-methyl-amino-acetato] cobalamin, (99m)Tc-PAMA-cobalamin). The derivative shows no binding to transcobalamin but is recognized by haptocorrin, a protein present in the circulation and notably expressed in many tumor cells. In this prospective study, we investigated cancer-specific uptake of (99m)Tc-PAMA-cobalamin in 10 patients with various metastatic tumors.

Objective: To determine the best predictor for the response to and survival with transarterial radioembolisation (RE) with 90yttrium microspheres in patients with liver metastases. Methods: Forty consecutive patients with liver metastases undergoing RE were evaluated with multiphase CT, perfusion CT and 99mTc-MAA SPECT. Arterial perfusion (AP) from perfusion CT, HU values from the arterial (aHU) and portal venous phase (pvHU) CT, and 99mTc-MAA uptake ratio of metastases were determined. Morphologic response was evaluated after 4months and available in 30 patients. One-year survival was calculated with Kaplan-Meier curves. Results: We found significant differences between responders and non-responders for AP (P 20ml/100ml/min had a significantly (P = 0.01) higher 1-year survival, whereas an aHU value >55 HU did not discriminate survival (P = 0.12). The Cox proportional hazard model revealed AP as the only significant (P = 0.02) independent predictor of survival. Conclusion: Compared to arterial and portal venous enhancement and the 99mTc-MAA uptake ratio of liver metastases, the AP from perfusion CT is the best predictor of morphologic response to and 1-year survival with RE. Key Points : • Perfusion CT allows for calculation of the liver arterial perfusion. • Arterial perfusion of liver metastases differs between responders and non-responders to RE. • Arterial perfusion can be used to select patients responding to RE.

Purpose To evaluate computed tomography (CT) perfusion for assessment of early treatment response after transarterial radioembolization of patients with liver malignancy. Materials and Methods Dynamic contrast-enhanced CT liver perfusion was performed before and 4 weeks after transarterial radioembolization in 40 patients (25 men and 15 women; mean age, 64 y ± 11; range, 35–80 y) with liver metastases (n = 27) or hepatocellular carcinoma (HCC) (n = 13). Arterial perfusion (AP) of tumors derived from CT perfusion and tumor diameters were measured on CT perfusion before and after transarterial radioembolization. Success of transarterial radioembolization was evaluated on morphologic follow-up imaging (median follow-up time, 4 mo) based on Response Evaluation Criteria in Solid Tumors (Version 1.1). CT perfusion parameters before and after transarterial radioembolization for different response groups were compared. Kaplan-Meier curves were plotted to illustrate overall 1-year survival rates. Results Liver metastases showed significant differences in AP before and after transarterial radioembolization in responders ( P P = .164). In HCC, AP values before and after transarterial radioembolization were not significantly different in responders and nonresponders ( P = .180 and P = .052). Tumor diameters were not significantly different on CT perfusion before and after transarterial radioembolization in responders and nonresponders with liver metastases and HCC ( P = .654, P = .968, P = .148, P = .164). In patients with significant decrease of AP in liver metastases after transarterial radioembolization, 1-year overall survival was significantly higher than in patients showing no reduction of AP. Conclusions CT perfusion showed early reduction of AP in liver metastases responding to transarterial radioembolization; tumor diameter remained unchanged early after treatment. No significant early treatment response to transarterial radioembolization was found in patients with HCC. In patients with liver metastases, a decrease of AP after transarterial radioembolization was associated with a higher 1-year overall survival rate.

Purpose: To compare the accuracy of PET/MR imaging with that of FDG PET/CT and to determine the MR sequences necessary for the detection of liver metastasis using a trimodality PET/CT/MR set-up. Methods: Included in this single-centre IRB-approved study were 55 patients (22 women, age 61 ± 11years) with suspected liver metastases from gastrointestinal cancer. Imaging using a trimodality PET/CT/MR set-up (time-of-flight PET/CT and 3-T whole-body MR imager) comprised PET, low-dose CT, contrast-enhanced (CE) CT of the abdomen, and MR with T1-W/T2-W, diffusion-weighted (DWI), and dynamic CE imaging. Two readers evaluated the following image sets for liver metastasis: PET/CT (set A), PET/CECT (B), PET/MR including T1-W/T2-W (C), T1-W/T2-W with either DWI (D) or CE imaging (E), and a combination (F). The accuracy of each image set was determined by receiver-operating characteristic analysis using image set B as the standard of reference. Results: Of 120 liver lesions in 21/55 patients (38%), 79 (66%) were considered malignant, and 63/79 (80%) showed abnormal FDG uptake. Accuracies were 0.937 (95% CI 89.5-97.9%) for image set A, 1.00 (95% CI 99.9-100.0%) for set C, 0.998 (95% CI 99.4-100.0%) for set D, 0.997 (95% CI 99.3-100.0%) for set E, and 0.995 (95% CI 99.0-100.0%) for set F. Differences were significant for image sets D-F (P

Objectives: Computed tomography perfusion (CTP) can provide information about angiogenesis and blood-flow characteristics in tumours. [18F]Fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) is one of the major oncological imaging techniques which provides information about viability of the tumour cell and partly also about its aggressiveness. The aim of the study was to investigate the relationship between FDG and CTP data in patients with head and neck cancers. Materials and methods: Forty-one patients with a clinically suspected head and neck cancer were prospectively included. All patients underwent a combined PET/CT with an integrated CTP examination in the area of the head and neck tumour. CTP data (BF, BV and MTT) and PET data (SUVmax, SUVmean, TLG, PETvol) were compared between tumours and (1) healthy contralateral tissue, (2) inflammatory lesions, (3) metastatic lymph nodes, and CTP data and PET data were correlated in tumours. Results: Thirty-five patients had a head and neck cancer. All CTP data were statistically different between tumours, inflammatory lesions, healthy tissue and metastatic lymph nodes; PET/CT data were in part significantly different. CTP and PET parameters were not significantly correlated. Conclusion: CTP and PET parameters were not significantly correlated; thus, the additional CTP values provide additional insights into tumour behaviour and their glycolytic status. Key Points : • Computed tomography perfusion (CTP) can be performed in combined positron emission tomography (PET)/CT. • CTP in addition to PET provides additional insights into tumour behaviour. • CTP can possibly differentiate between head and neck tumours and inflammatory lesions. • PET/CT with integrated CTP is possible without additional contrast media

To prospectively analyze the correlation between parameters of liver perfusion from technetium99m-macroaggregates of albumin (99mTc-MAA) single photon emission computed tomography (SPECT) with those obtained from dynamic CT perfusion in patients with primary or metastatic liver malignancy.Twenty-five consecutive patients (11 women, 14 men; mean age 60.9 ± 10.8; range: 32-78 years) with primary (n = 5) or metastatic (n = 20) liver malignancy planned to undergo selective internal radiotherapy underwent dynamic contrast-enhanced CT liver perfusion imaging (four-dimensional spiral mode, scan range 14.8 cm, 15 scans, cycle time 3 seconds) and 99m)Tc-MAA SPECT after intraarterial injection of 180 MBq 99mTc-MAA on the same day. Data were evaluated by two blinded and independent readers for the parameters arterial liver perfusion (ALP), portal venous perfusion (PVP), and total liver perfusion (TLP) from CT, and the 99mTc-MAA uptake-ratio of tumors in relation to normal liver parenchyma from SPECT.Interreader agreements for quantitative perfusion parameters were high for dynamic CT (r = 0.90-0.98, each P.01) and 99mTc -MAA SPECT (r = 0.91, P.01). Significant correlation was found between 99mTc-MAA uptake ratio and ALP (r = 0.7, P.01) in liver tumors. No significant correlation was found between 99mTc-MAA uptake ratio, PVP (r = -0.381, P = .081), and TLP (r = 0.039, P = .862).This study indicates that in patients with primary and metastatic liver malignancy, ALP obtained by dynamic CT liver perfusion significantly correlates with the 99mTc-MAA uptake ratio obtained by SPECT.

PURPOSE: To assess the possible radiosensitizing capabilities of two different poly(ADP-ribose) polymerase (PARP) inhibitors in combination with external beam and I-tositumomab in a non-Hodgkin's lymphoma cell line. METHODS AND MATERIALS: Epstein-Barr virus-infected human Raji lymphoma cells with lentivirally transfected green fluorescent protein and luciferase in log-phase growth were incubated with various doses of AZD-2281 and ABT-888 24 h before external beam radiation exposure. A 500 nmol/l concentration of AZD-2281 and ABT-888 was used to assess the growth curve of Raji lymphoma cells over 5 days. The number of double-stranded breaks was visually assessed using a H2AX antibody and confocal microscopy. Intracellular PARP activity was measured 2 h after incubation with AZD-2281 (500 nmol/l) and ABT-888 using a colorimetric PARP assay kit. The radiosensitizing effect of AZD-2281 (500 nmol/l) with various doses of I-tositumomab was assessed after 24 h. RESULTS: A volume of 500 nmol/l of AZD-2281 and 500 nmol/l of ABT-888, in combination with 0, 4, 8, and 12 Gy external beam radiation, showed a 5.2, 7.1, 10.1, and 33.1% radiosensitization. A measure of 500 nmol/l AZD-2281 and ABT-888 significantly reduced the percentage of viable cells on days 3-5 compared with controls. The maximal relative reduction in viable cells was 78.5%, and this occurred with AZD-2281 (500 nmol/l) on day 5. AZD-2281 revealed a higher number of double-stranded breaks with confocal microscopy than did ABT-888. Two hours after incubation of Raji cells with 500 nmol/l of AZD-2281 or ABT-888, the colorimetric PARP activity assay showed a reduction of 30.36% with ABT-888 and of 47.8% with AZD-2281. Combining AZD-2281 (500 nmol/l) with 0, 5 μCi (0.185 MBq), 10 μCi (0.37 MBq) and 20 μCi (0.74 MBq) ¹³¹I-tositumomab revealed a significant reduction in cell viability after 24 h with 5 μCi (0.185 MBq) (P

The Warburg hypothesis states that aggressive cancers obtain much of their adenosine triphosphate (ATP) by metabolizing glucose directly to lactic acid. As a result of its high tumor selectivity, 3-bromopyruvic acid (3-BrPA), a well-known inhibitor of energy metabolism, has been proposed as a specific anticancer agent. We investigated the effect of 3-BrPA in a mouse model of aggressive metastatic lymphoma. Epstein-Barr-virus-infected human Raji lymphoma cells with lentivirally transfected green fluorescent protein and luciferase were incubated with RPMI/fetal bovine serum, and various concentrations of 3-BrPA were used to determine the LD50 in vitro. In total, 18 severely combined immunodeficient mice were injected with 1 million human Raji lymphoma cells via the tail vein. Using bioluminescent imaging, tumor growth was measured daily for 12 days to determine the tumor burden. At day 0 (start of treatment), the mice were randomized. Six mice received 10 mg/kg 3-BrPA i.p. daily for 7 days, 6 mice received 1 treatment at day 0, and 6 mice received the control buffer. Tumor growth was assessed daily from day 0 until day 7 using bioluminescent imaging. All data were normalized to acquisition time (luminescence/second; L/s). Body weight was measured daily to determine the toxicity of 3-BrPA. The LD50 for Raji lymphoma cells exposed to 3-BrPA in vitro was 11 μM with an extremely steep dose response curve. At day 0, tumor activity medians in the group with daily treatment was 2131 L/s (244-12,725), with a 1-day dose of 3095 L/s (523-9650) and in the nontreated control group, 2997 L/s (1521-6911). In mice treated with a daily dose of 10 mg/kg 3-BrPa for 7 days, a significant reduction in tumor activity was found during the whole treatment period compared with the control mice (P = 0.0043 at day 7). In mice with a single treatment at day 0, growth delay was only evident at day 2 (P = 0.0152 at day 2) but not for the rest of the observation period. The only manifestation of toxicity of the daily administration of 10 mg/kg 3-BrPA was a reduction in body weight. Body weight at day 0 was 17.22 g ± 0.84 g in the treatment group and 17.58 g ± 0.86 g in the control group. Body weight at day +6 was 15.02 g ± 2.04 g in the treated group and 19.4 g ± 0.63 g in the control group. 3-BrPA demonstrated a significant positive tumor response both in vitro and in vivo. This, to our knowledge, is the first report of the use of 3-BrPA in a systemic tumor model. Based on these data, 3-BrPA holds promise for treatment of systemic metastatic cancers.

Antibody responses to tumor antigens play an important role in initiating a cellular antitumor response with respect to antigen cross-presentation and T cell cross-priming. Successful vaccination strategies rely on an optimally timed activation of the humoral and cellular immune system by using appropriate adjuvant stimulation. The LUD99-008 trial used the cancer testis antigen NY-ESO-1 formulated with ISCOMATRIX adjuvant injected into patients intramuscularly. It was shown that this vaccination strategy is a safe and highly potent activator of the humoral and cellular immune system. Using the RAYS technology, we analyzed in detail the humoral immune response in these patients before and after vaccination: during the course of repeated vaccinations with the adjuvant, antibody titers against NY-ESO-1 and cross-reactivity to LAGE 1A and B increased as an indicator of an enhanced immune response, whereas no antibody response could be detected after vaccination without the adjuvant. Analysis of single fragments of the NY-ESO-1 protein revealed that the humoral response was almost exclusively directed against the N-terminal fragments and the number of fragments and their length being recognized by the NY-ESO-1-specific antibodies increased during the course of vaccination. The humoral immune response mainly consisted of antibodies of the IgG1 and IgG3 subclass. We rarely found IgG2 and IgG4 subclass antibodies. Our results support the implication that target-specific antibodies raised after vaccination contribute to the stimulation of an effective T cell response against the target antigen.

Despite approval by the Food and Drug Administration and consistent reports of the efficacy and safety of (90)Y-ibritumomab tiuxetan and (131)I-tositumomab, these therapies are infrequently used. This study investigates the opinions and patterns of the use of radioimmunotherapy by nuclear physicians, affiliated researchers, nuclear medicine technologists, and radiation oncologists and aims to identify possible barriers to the use of this promising therapy.An e-mail-based survey with 13 broad questions related to radioimmunotherapy was sent electronically to 13,221 Society of Nuclear Medicine members and radiation oncologists throughout the United States.Six hundred thirteen individuals (4.6%) responded to the electronic survey. Two hundred fifty-one responders (40.9%) had treated patients with non-Hodgkin lymphoma (NHL) with radioimmunotherapy in the last 24 mo. Of the responders, 29.5% used only (90)Y-ibritumomab tiuxetan, 7.6% used only (131)I-tositumomab, and 24.9% used both radiopharmaceuticals; 37.9% did not treat NHL with radioimmunotherapy. Most responders said their patients came from university hospitals (33.9%) or private offices (25.6%), and they mainly treated in a second-line (42.9%), third-line (35.6%), or consolidation (23.5%) setting. Major concerns were that referring oncologists and hematologists wanted to treat by themselves with nonradioactive compounds (mean ± SD, 3.418 ± 1.49) and that (90)Y-ibritumomab tiuxetan and (131)I-tositumomab were expensive (mean ± SD, 3.413 ± 1.35). Of the responders and involved physicians, 40.4% and 35.2%, respectively, did not know if their institution accepted Medicare patients for radioimmunotherapy. Almost 30% (29.6%) of the responders thought radioimmunotherapy would probably grow and 38.0% thought it would grow in importance in the future. Responders who did not administer radioimmunotherapy for NHL thought it took too much time to administer radioimmunotherapy (P0.01) and had concerns about the dosimetry procedure (P0.01) and radiation safety (P0.01). Individuals who perceived a negative future for radioimmunotherapy had significantly more concerns about the time-consuming administration process (P0.05) and the high cost of radioimmunotherapy (P0.05). Responders from academic centers had significantly fewer concerns about payment (P0.01), dosimetry (P0.01), and radiation safety (P0.01).Radioimmunotherapy was generally viewed positively by the surveyed population. However, limited referrals due to alternative nonradioactive therapies and logistic, educational, and economic concerns played an important role for subgroups in the perception of radioimmunotherapy for NHL.

Objective: To assess the clinical value of multi-phase, contrast-enhanced DOPA-PET/CT with emphasis on the diagnostic CT component in patients with neuroendocrine tumours (NET). Methods: Sixty-five patients with NET underwent DOPA-cePET/CT. The DOPA-PET, multi-phase CT and combined DOPA cePET/CT data were evaluated and diagnostic accuracies compared. The value of ceCT in DOPA cePET/CT concerning lesion detection and therapeutic impact was evaluated. Sensitivities, specificities and accuracies were calculated. Histopathology and clinical follow-up served as the standard of reference. Differences were tested for statistical significance by McNemar's test. Results: In 40 patients metastatic and/or primary tumour lesions were detected. Lesion-based analysis for the DOPA-PET showed sensitivity, specificity and accuracy of 66%, 100% and 67%, for the ceCT data 85%, 71% and 85%, and for the combined DOPA cePET/CT data 97%, 71% and 96%. DOPA cePET/CT was significantly more accurate compared with dual-phase CT (p

507 Objectives To investigate the benefit of including the brain in the field of view (FOV) of FDG-PET/CTscan in patients with malignant melanoma (MM). Methods Between 01-04-2008 and 30-11-2009 the local database was searched for MM patients who underwent FDG-PET/CT (with inclusion of the entire brain in the FOV) and MRI within 3 months time period. A total of 49 examinations were obtained in 34 patients (17 male, 17 female; mean age 52.7, range 26-80 years) and investigated. According to the AJCC classification 24 patients with stage IV, 7 stage I and 3 stage II were included. The CT part was acquired after IV contrast administration in the venous phase. Gadolinium-enhanced MRI was considered as the gold standard. The average time interval between PET/CT and MRI was 15.8 days. Results On FDG-PET/CT 73 suspected lesions were identified: 3 presented with altered (hyper-)metabolism only, 36 were only seen on CT and 34 were identified on both PET and CT (8 hyper- and 26 hypometabolic). MRI detected 133 lesions, resulting in a sensitivity and accuracy of FDG-PET/CT of 55%. Specificity could not be calculated since there were no true negative lesions present. On scan basis 22/49 FDG-PET/CT examinations were classified as positive. MRI demonstrated the presence of brainmetastases in 23 scans. All of the FDG-PET/CT positive cases were confirmed using MRI. In 18 cases suspected lesions were identified as well on FDG-PET as on contrast enhanced CT, while 4 cases were seen on CT only. In determining the existence of brainmetastases, the sensitivity, specificity and accuracy of the FDG-PET/CT scans in comparison with MRI was 96%, 100% and 98% respectively. Conclusions FDG-PET/CT with the use of contrast enhanced CT and acquisition in the venous phase performs well compared with contrast enhanced MRI in demonstrating the presence of brainmetastases in known MM. In case of negative FDG-PET/CT and suspected clinical findings a contrast enhanced MR remains mandatory

Background: The purpose of this study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) during follow-up of patients with diffuse large B-cell lymphoma (DLBCL) being in complete remission or unconfirmed complete remission after first-line therapy. Patients and methods: DLBCL patients receiving FDG-PET/CT during follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in cases of suspected disease recurrence. Results: Seventy-five patients were analyzed and 23 (30%) had disease recurrence. The positive predictive value (PPV) of FDG-PET/CT was 0.85. Patients >60 years [P = 0.036, hazard ratio (HR) = 3.82, 95% confidence interval (CI) 1.02-7.77] and patients with symptoms indicative of a relapse (P = 0.015; HR = 4.1; 95% CI 1.20-14.03) had a significantly higher risk for relapse. A risk score on the basis of signs of relapse, age >60 years, or a combination of these factors identified patients at high risk for recurrence (P = 0.041). Conclusions: FDG-PET/CT detects recurrent DLBCL after first-line therapy with high PPV. However, it should not be used routinely and if only in selected high-risk patients to reduce radiation burden and costs. On the basis of our retrospective data, FDG-PET/CT during follow-up is indicated for patients 60 years with and without clinical signs of relapse