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Background Integrin alpha-V-beta-3 (αvβ3) pathway is involved in intraplaque angiogenesis and inflammation and represents a promising target for molecular imaging in cardiovascular diseases such as atherosclerosis. The aim of this study was to assess the clinical correlates of arterial wall accumulation of 68Ga-NODAGA-RGD, a specific αvβ3 integrin ligand for PET. Materials and methods The data of 44 patients who underwent 68Ga-NODAGA-RGD PET/CT scans were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed semi-quantitatively by blood-pool-corrected target-to-background ratios. Tracer uptake was compared with clinically documented atherosclerotic cardiovascular disease, cardiovascular risk factors and calcified plaque burden. Data were compared using the Mann–Whitney U test, Pearson correlation and Spearman correlation. Results 68Ga-NODAGA-RGD arterial uptake was significantly higher in patients with previous clinically documented atherosclerotic cardiovascular disease (mean TBR 2.44 [2.03–2.55] vs. 1.81 [1.56–1.96], p = 0.001) and showed a significant correlation with prior cardiovascular or cerebrovascular event (r = 0.33, p = 0.027), BMI (ρ = 0.38, p = 0.01), plaque burden (ρ = 0.31, p = 0.04) and hypercholesterolemia (r = 0.31, p = 0.04). Conclusions 68Ga-NODAGA-RGD holds promise as a non-invasive marker of disease activity in atherosclerosis, providing information about intraplaque angiogenesis.

Highlights • Abscopal effect is the ability of local RT to induce systemic antitumor effect. • Abscopal effect is increasingly frequent with concomitant immunotherapy and RT. • Abscopal effect remains a rare observation. • We report an abscopal effect in MPM treated with concomitant anti-PD-L1 and RT., The abscopal effect describes the ability of locally administered radiotherapy to induce systemic antitumor effects. Although mentioned for the first time in the 1950s, records of abscopal effects, considered to be immune-mediated, are scarce with radiotherapy alone. However, with the continued development and use of immunotherapy, reports on the abscopal effect have become increasingly frequent during the last decade. Here, we report a patient with advanced malignant pleural mesothelioma who had progressive disease while on the anti-PDL1 inhibitor pembrolizumab and showed an abscopal response after palliative radiotherapy.

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.

Incidental 18F-FDG uptake in the pituitary may be detected during PET examinations. We aimed to perform a systematic review and a meta-analysis about prevalence and clinical significance of this finding. A comprehensive computer literature search, using several databases, was performed until March 2020. Pooled prevalence and rate of malignancy, including 95% confidence interval values (95% CI), were calculated on a per-examination based analysis. Five studies (180 cases of incidental 18F-FDG uptake in the pituitary) were included; most of the cases were further evaluated with MRI. The pooled prevalence of incidental 18F-FDG uptake in the pituitary was 0.33% (95% CI 0.07–0.78%). Adenomas were the most frequent lesions underlying an incidental 18F-FDG uptake in the pituitary when further evaluated with MRI (pooled prevalence: 66%; 95% CI 42–86%). The pooled rate of malignancy in cases of incidental 18F-FDG uptake further evaluated with MRI was 13% (95%CI 3–31%). Notably, a significant heterogeneity among the selected studies was found. Of note, in the available series, there were not patients with incidental 18F-FDG uptake in the pituitary treated with immunotherapy. Clinicians, radiologists and nuclear medicine physicians should be aware that incidental 18F-FDG uptake in the pituitary is an infrequent finding corresponding to benign lesions in most of the cases. Nevertheless, if the patient has normal life expectancy, MRI pituitary examination should be performed to better characterize these incidental findings due to possible clinical consequences of some pituitary incidentalomas if untreated. Further well-designed studies are needed on this topic, especially in view of the increasing frequency of immunotherapy, whose side-effects can be seen by increased 18F-FDG uptake in the pituitary.

Immunotheranostics will be an important development in the future of nuclear medicine and medical oncology. It describes the synergy of theranostic procedures in nuclear medicine and immune oncology (IO) treatment. In brief, it takes advantage of molecular imaging and subsequent targeted modulation of the-in most cases immunosuppressive-tumor microenvironment (TME) by diagnostic and therapeutic radioisotopes. This is of high importance since only a fraction of patients receiving IO is currently being cured by this exciting therapy option. We therefore envision the concept of immunotheranostics as a powerful mean to augment the success of IO treatment in the future and thus the urgent need to further develop the interaction and joint action of nuclear medicine and medical oncology for substantially improved therapy outcome for cancer patients.

Purpose The aim of this study was to assess the most reliable quantitative variable on Rubidium-82 (82Rb) cardiac PET/CT for predicting major adverse cardiovascular events (MACE), on the latest PET camera using silicon photomultipliers digital readout (SiPM) technology. Methods We prospectively enrolled 274 consecutive participants with suspected myocardial ischemia. Participants underwent 82Rb cardiac SiPM PET/CT and were followed-up for MACE over 652 days (interquartile range: 559 to 751 days). For each participant, global and regional myocardial flow reserve (MFR), stress myocardial blood flow (stress MBF) and their combination as myocardial flow capacity radius (MFC radius) were measured. Results On receiver operator curve analysis, MACE prediction was similar for global and regional MFR, stress MBF, and MFC radius (area under the curve; (i) Global: 0.70 vs. 0.71 and 0.73, and (ii) Regional: 0.71 vs. 0.71 and 0.73, respectively, p > 0.1 for all pairwise comparisons). On multivariable analysis, (i) Global: MFR < 1.98, stress MBF < 1.94 mL/g/min, and MFC radius < 3.12, as well as (ii) Regional: MFR < 1.75, stress MBF < 1.75 mL/g/min, and MFC radius < 2.7, emerged all as similar independent predictors of MACE (p < 0.001 for all). Conclusions Using the latest SiPM PET technology with 82Rb, global and regional MFR, stress MBF, and MFC radius are similar powerful predictors of cardiovascular event.

Mesothelioma is a malignancy of serosal membranes. Parietal pleura is the most common site, with peritoneum being the second most frequent location. Malignant peritoneal mesothelioma (MPM) is a rare and aggressive disease. The prognosis is often very poor with median overall survival ranging from 6 to 18 months in patients who are not candidates for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) due to non-resectable disease or comorbid conditions. For patients with resectable disease, CRS and HIPEC have become the standard of care. However, for patients with unresectable malignant mesothelioma there is unfortunately no effective systemic treatment beyond the first line. Based on the results of a recent phase II trial, lurbinectedin has clinical activity and acceptable toxicity in the second- and third-line treatment of malignant pleural mesothelioma. However, until present, no data have been available for patients with MPM and for patients who become refractory after multiple treatment lines. We report on two patients with metastatic MPM who achieved durable disease control of 10+ and 8 months with lurbinectedin in the fourth and fifth treatment line, respectively.

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.

Zusammenfassung. Die Nuklearmedizinische befasst sich mit der Bildgebung, Therapie und Theranostik mittels radioaktaktiver Elemente gebunden an zielgerichtete Trägermoleküle, sogenannte Radiotracer. Insbesondere die moderne Onkologie profitiert von den zunehmenden diagnostischen Möglichkeiten, zum Beispiel im Rahmen der immer präziseren Ausbreitungsdiagnostik von Tumoren oder der frühzeitigen Messung vom Ansprechen von Tumoren unter gezielten Therapien. Die moderne Nuklearmedizin bietet ebenfalls neue und innovative Methoden zur Behandlung spezieller Tumortypen an. Neue verfügbare Therapien umfassen zum Beispiel das metastasierte Prostatakarzinom, während weitere Methoden zum Beispiel für das Mamma- und Lungenkarzinom oder das Pankreaskarzinom aktuell in klinischen Studien überprüft werden. Die Nuklearmedizin wird durch die Theranostik komplettiert wobei therapeutische und diagnostische Methoden kombiniert werden. Insbesondere in moderne, personalisierte Onkologie mit all ihren zielgerichteten Therapien profitiert von diesen Methoden um das Therapieansprechen, im zeitlichen Verlauf vorherzusagen.

Anti-PD-1/PD-L1 blockade can restore tumour-specific T-cell immunity and is an emerging therapy in non-small-cell lung cancer (NSCLC). We investigated the correlation between 18F-FDG PET/CT-based markers and tumour tissue expression of PD-L1, necrosis and clinical outcome in patients receiving checkpoint inhibitor treatment. PD-Li expression in biopsy or resection specimens from 49 patients with confirmed NSCLC was investigated by immunohistochemistry. Maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were obtained from 18F-FDG PET/CT images. The ratio of metabolic to morphological lesion volumes (MMVR) and its association with PD-L1 expression in each lesion were calculated. The associations between histologically reported necrosis and 18F-FDG PET imaging patterns and radiological outcome (evaluated by iRECIST) following anti-PD-1/PD-L1 therapy were also analysed. In 14 patients, the association between necrosis and MMVR and tumour immune contexture were analysed by multiple immunofluorescent (IF) staining for CD8, PD-1, granzyme B (GrzB) and NFATC2. In total, 25 adenocarcinomas and 24 squamous cell carcinomas were analysed. All tumours showed metabolic 18F-FDG PET uptake. MMVR was correlated inversely with PD-L1 expression in tumour cells. Furthermore, PD-L1 expression and low MMVR were significantly correlated with clinical benefit. Necrosis was correlated negatively with MMVR. Multiplex IF staining showed a greater frequency of activated CD8+ cells in necrotic tumours than in nonnecrotic tumours in both stromal and epithelial tumour compartments. This study introduces MMVR as a new imaging biomarker and its ability to noninvasively capture increased PD-L1 tumour expression and predict clinical benefit from checkpoint blockade in NSCLC should be further evaluated.

Imaging of neuroendocrine neoplasms (NENs) is extremely rich and varied. Conventional techniques of morphological imaging (ultrasound, CT, MRI) are complementary to other imaging techniques such as endoscopic explorations and functional imaging using radiopharmaceutical imaging techniques. NENs have very distinct functional characteristics, which make them ideal targets for functional molecular imaging. Functional imaging plays a crucial role in the assessment of initial tumor distribution (staging), disease assessment after therapy (restaging), disease follow-up, and planning for somatostatin receptor (SSTR) 2-based radiopeptide treatment. Other tracers, such as 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy or 18F-DOPA (dihydroxyphenylalanine) and the SSTR2-antagonist (NODAGA-JR11) PET/CT have been developed for specific indications or to gain sensitivity and specificity. The more aggressive, less differentiated neuroendocrine carcinomas tend to have less SSTR2 receptor expression, and the tumor cell metabolism shifts toward anaerobic glycolysis. In these patients, receptor-based imaging should be complemented or replaced by metabolic 18F-FDG (18F-fluorodeoxyglucose) PET/CT. The continuum from well-differentiated neuroendocrine tumor to a more aggressive neuroendocrine carcinoma makes functional imaging sometimes challenging.

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.

This chapter summarizes 15 meta-analyses published in the literature on the use of PET for cardiac diseases, with the majority (n = 8) concerning the diagnosis of coronary artery disease (CAD) using myocardial perfusion imaging (MPI) in comparison to other modalities. Second in the number of published meta-analyses, three studies concentrated on the prognostic value of MPI for adverse cardiovascular events. Finally, one meta-analysis was published on the use of PET for four indications among myocardial viability assessment, the presence of microvascular disease (impaired coronary vascular function in absence of obstructive, epicardial CAD), the use of cardiac hybrid imaging and the diagnostic of cardiac amyloidosis.

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.

Purpose To compare the value of pretreatment functional and morphological imaging parameters for predicting survival in patients undergoing transarterial radioembolization using yttrium-90 (90Y-TARE) for unresectable hepatocellular carcinoma (uHCC).

The aim of this study was to compare survival of patients treated for unresectable hepatocellular carcinoma (uHCC) with Yttrium-90 (90Y) transarterial radioembolization (TARE) using pretreatment partition model dosimetry (PMD). Methods: We performed a retrospective analysis of prospectively collected data on 77 consecutively treated (mean age 66.4 12.2 y) for uHCC (36 uni-nodular, 5 multi-nodular, 36 diffuse) with 90Y TARE (41 resin, 36 glass) using pretreatment PMD. Study endpoints were progression-free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier estimates. Several variables including Barcelona Clinic Liver Cancer (BCLC) staging system, tumor size and serum alpha-fetoprotein (AFP) level) were investigated using Cox proportional hazards regression. Results: Characteristics of two groups were comparable in regard to demographic data, comorbidities, Child-Pugh score, BCLC, serum AFP level and 90Y global administered activity. Median follow-up time was 7.7 months (range 0.4-50.1). Relapse occurred in 44 patients (57%) at a median of 6 mo (range 0.4-27.9) after 90Y TARE and 41 patients (53%) died from tumor progression. Comparison between resin and glass microspheres revealed a higher but not statistically significantly PFS and OS rates in 90Y resin group compared to 90Y glass group (resin PFS 6.1 mo [95% Confidence interval CI 4.7-7.4] and glass PFS 5 mo [95% CI 0.9-9.2], P = 0.53; resin OS 7.7 mo [95% CI 7.2-8.2] and glass OS 7 mo [95% CI 1.6-12.4], P = 0.77). No significant survival difference between both types of 90Y microspheres was observed in any subgroups of patients with early/intermediate or advanced BCLC stages. Among the variables investigated Cox analyses showed that only in the glass group, the BCLC staging system and the serum AFP level were associated with PFS (P = 0.04) and OS (P = 0.04). Tumor size was a prognostic factor without significant influence on PFS and OS after 90Y TARE. Conclusion: Comparison between resin and glass microspheres revealed no significant survival difference in patients treated for uHCC with 90Y TARE using pretreatment PMD. Further larger prospective studies are warranted to confirm these findings.

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.

Background: Tumor-induced or oncogenic osteomalacia (TIO) is a rare paraneoplastic syndrome in which osteomalacia is a consequence of fibroblast growth factor 23 (FGF23) secretion by a mesenchymal tumor. The localization of the culprit lesion in patients with TIO is often challenging. Several studies have evaluated the detection rate (DR) of these tumors using somatostatin receptor positron emission tomography (SSTR-PET/CT). We aimed to summarize literature findings on this topic providing pooled estimates of DR. Methods: A comprehensive literature search by screening PubMed, Embase and Cochrane library electronic databases through August 2019 was performed. The pooled DR of culprit tumors using SSTR-PET/CT in patients with TIO was calculated using a random-effects statistical model. Results: Fourteen studies on the use of SSTR-PET/CT in detecting the culprit tumor in patients with TIO were included in the qualitative analysis. The pooled DR of SSTR-PET/CT on a per-patient-based analysis calculated using eleven studies (166 patients) was 87.6% (95% confidence interval (95% CI) 80.2–95.1%). Statistical heterogeneity among studies was detected (I-square = 63%), likely due to the use of different radiolabeled somatostatin analogues, as demonstrated by a subgroup analysis. Conclusions: Despite limited literature data due to the rarity of the disease, SSTR-PET/CT demonstrated a very high DR of culprit tumors in patients with TIO and it could be used as first-line imaging method for this indication.

We are continuously progressing in our understanding of cancer and other diseases and learned how they can be heterogeneous among patients. Therefore, there is an increasing need for accurate characterization of diseases at the molecular level. In parallel, medical imaging and image-guided therapies are rapidly developing fields with new interventions and procedures entering constantly in clinical practice. Theranostics, a relatively new branch of medicine, refers to procedures combining diagnosis and treatment, often based on patient and disease-specific features or molecular markers. Interventional oncology which is at the convergence point of diagnosis and treatment employs several methods related to theranostics to provide minimally invasive procedures tailored to the patient characteristics. The aim is to develop more personalized procedures able to identify cancer cells, selectively reach and treat them, and to assess drug delivery and uptake in real-time in order to perform adjustments in the treatment being delivered based on obtained procedure feedback and ultimately predict response. Here, we review several interventional oncology procedures referring to the field of theranostics, and describe innovative methods that are under development as well as future directions in the field.

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.

This is the first described case of effective and durable cytoreduction after PRRT with 177Lu-DOTATATE in a 75-year-old female, with B cell chronic lymphoid leukemia, and well-differentiated metastatic neuroendocrine tumor.

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.

SIRT (selective internal radiation therapy) is a widely used form of intra-arterial treatment for patients with advanced liver primary and secondary tumors of the liver. The relatively selective arterial perfusion via the hepatic artery of growing liver tumors makes intra-arterial treatment an near ideal concept for these patients. Nevertheless the procedure needs technical and dosimetry skills which are summarized in this chapter. Furthermore, the clinical data in context to intravenous therapies need to be acknowledged mainly in discussion with multidisciplinary tumor boards. Therefore this chapter also summarizes important studies in the field. Finally, measurement outcome remains a challenge and are also discussed in the last paragraph.

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

To generate a predictive whole-liver radiomics scoring system for progression-free survival (PFS) and overall survival (OS) in patients undergoing transarterial radioembolization using Yttrium-90 ( 90 Y-TARE) for unresectable hepatocellular carcinoma (uHCC). The generated pPET-RadScores were significantly correlated with survival for PFS (median of 11.4 mo [95% confidence interval CI: 6.3-16.5 mo] in low-risk group [PFS-pPET-RadScore < 0.09] vs. 4.0 mo [95% CI: 2.3-5.7 mo] in high-risk group [PFS-pPET-RadScore > 0.09]; P = 0.0004) and OS (median of 20.3 mo [95% CI: 5.7-35 mo] in low-risk group [OS-pPET-RadScore < 0.11] vs. 7.7 mo [95% CI: 6.0-9.5 mo] in high-risk group [OS-pPET-RadScore > 0.11]; P = 0.007). The multivariate analysis confirmed PFS-pPET-RadScore ( P = 0.006) and OS-pPET-RadScore ( P = 0.001) as independent negative predictors. Pretreatment 18 F-FDG PET whole-liver radiomics signature appears as an independent negative predictor for PFS and OS in patients undergoing 90 Y-TARE for uHCC. Pretreatment 18 F-FDG PET of 47 consecutive patients undergoing 90 Y-TARE for uHCC (31 resin spheres, 16 glass spheres) were retrospectively analyzed. For each patient, based on PET radiomics signature from whole-liver semi-automatic segmentation, PFS and OS predictive PET-radiomics scores (pPET-RadScores) were obtained using LASSO Cox regression. Using X-tile software, the optimal score to predict PFS (PFS-pPET-RadScore) and OS (OS-pPET-RadScore) served as cutoff to separate high and low-risk patients. Survival curves were estimated using the Kaplan-Meier method. The prognostic value of PFS and OS-pPET-RadScore, Barcelona-Clinic Liver Cancer staging system and serum alpha-fetoprotein level was analyzed to predict PFS and OS in multivariate analysis.

(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.

RATIONALE AND OBJECTIVES: To prospectively analyze the correlation between parameters of liver perfusion from technetium(99m)-macroaggregates of albumin ((99m)Tc-MAA) single photon emission computed tomography (SPECT) with those obtained from dynamic CT perfusion in patients with primary or metastatic liver malignancy. MATERIALS AND METHODS: 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 (99m)Tc-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 (99m)Tc-MAA uptake-ratio of tumors in relation to normal liver parenchyma from SPECT. RESULTS: Interreader agreements for quantitative perfusion parameters were high for dynamic CT (r = 0.90-0.98, each P < .01) and (99m)Tc -MAA SPECT (r = 0.91, P < .01). Significant correlation was found between (99m)Tc-MAA uptake ratio and ALP (r = 0.7, P < .01) in liver tumors. No significant correlation was found between (99m)Tc-MAA uptake ratio, PVP (r = -0.381, P = .081), and TLP (r = 0.039, P = .862). CONCLUSION: This study indicates that in patients with primary and metastatic liver malignancy, ALP obtained by dynamic CT liver perfusion significantly correlates with the (99m)Tc-MAA uptake ratio obtained by SPECT.

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

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.

Background: The unique situation of the liver with arterial and venous blood supply and the dependency of the tumor on the arterial blood flow make this organ an ideal target for intrahepatic catheter-based therapies. Main forms of treatment are classical bland embolization (TAE) cutting the blood flow to the tumors, chemoembolization (TACE) inducing high chemotherapy concentration in tumors, and radioembolization (TARE) without embolizing effect but very high local radiation. These different forms of therapies are used in different centers with different protocols. This overview summarizes the different forms of treatment, their indications and protocols, possible side effects, and available data in patients with non-colorectal liver tumors. Methods: A research in PubMed was performed. Mainly clinical controlled trials were reviewed. The search terms were ‘embolization liver', ‘TAE', ‘chemoembolization liver', ‘TACE', ‘radioembolization liver', and ‘TARE' as well as ‘chemosaturation' and ‘TACP' in the indications ‘breast cancer', ‘neuroendocrine', and ‘melanoma'. All reported studies were analyzed for impact and reported according to their clinical relevance. Results: The main search criteria revealed the following results: ‘embolization liver + breast cancer', 122 results, subgroup clinical trials 16; ‘chemoembolization liver + breast cancer', 62 results, subgroup clinical trials 11; ‘radioembolization liver + breast cancer', 37 results, subgroup clinical trials 3; ‘embolization liver + neuroendocrine', 283 results, subgroup clinical trials 20; ‘chemoembolization liver + neuroendocrine', 202 results, subgroup clinical trials 9; ‘radioembolization liver + neuroendocrine', 64 results, subgroup clinical trials 9; ‘embolization liver + melanoma', 79 results, subgroup clinical trials 15; ‘chemoembolization liver + melanoma', 60 results, subgroup clinical trials 14; ‘radioembolization liver + melanoma', 18 results, subgroup clinical trials 3. The term ‘chemosaturation liver' was tested without indication since only few publications exist and provided us with five results and only one clinical trial. Conclusion: Despite many years of clinical use and documented efficacy on intra-arterial treatments of the liver, there are still only a few prospective multicenter trials with many different protocols. To guarantee the future use of these efficacious therapies, especially in the light of many systemic or surgical therapies in the treatment of non-colorectal liver metastases, further large randomized trials and transparent guidelines need to be established.

4094Background: Response evaluation with RECIST has limitations when applied to slow growing malignancies with low objective response rates, such as NETs, when most pts achieve SD as best response....

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

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.

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

Preclinical data indicated a detrimental effect of statins on the anti-lymphoma activity of rituximab. We evaluated the impact of concomitant statin medication on the response and survival of patients with diffuse large B cell lymphoma (DLBCL) receiving rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) as first-line therapy. Medical histories of patients with DLBCL who were treated with R-CHOP as first-line therapy were assessed for concomitant statin use, response after completion of chemotherapy, event-free survival (EFS), and overall survival (OS). Furthermore, 2-[(18)F]fluor-2-deoxyglucose (FDG)-PET/CT results after completion of first-line therapy were compared between the groups. Overall, 145 patients with DLBCL treated with R-CHOP from January 2001 to December 2009 were analyzed. Twenty-one (15%) patients received statins throughout therapy. Five-year EFS was 67.3% in patients without statins compared with 79% in patients receiving statins during R-CHOP (HR, 0.47; 95% CI, 0.15-1.54, p = 0.2). Five-year OS was 81.4% for patients without statins compared with 93.3% for patients taking statins (HR, 0.58; 95% CI 0.07-4.55, p = 0.6). There were no statistically significant differences in the rates of complete remissions between the two groups (75% in the non-statin group versus 86% in the statin group, p = 0.45). A trend toward a lower rate of complete metabolic responses in FDG-PET/CT after chemotherapy was seen in patients without statin medication compared with the patients taking statins (84% versus 92%, p = 0.068). Concomitant statin use had no adverse impact on response to chemotherapy, EFS, and OS in patients treated with R-CHOP for DLBCL.

OBJECTIVES/HYPOTHESIS: Using a retrospective approach, the aim of this study was to confirm the previously described value of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in patients with primary extranodal lymphoma of the head and neck region. Additionally, the clinical significance of the semiquantitative analysis of the standardized uptake value (SUV), its predictive role in the follow-up setting, and its value in detection of synchronous primaries were studied. STUDY DESIGN: Retrospective chart review. METHODS: Twenty-six patients with a primary extranodal head and neck lymphoma (22 diffuse large B-cell lymphoma, one Hodgkin's lymphoma, three malignant T-cell lymphomas) were included. We retrospectively evaluated the clinical outcomes according to the maximum standardized uptake values of the primary lesion (SUV(max)) and whether a positron emission tomography/computed tomography (PET/CT) was performed or not in the follow-up studies. The median SUV(max) was chosen as the cutoff value. The patients were then grouped as those with either low or high SUV(max), respective to the cutoff value. Event-free survival and cumulative survival were endpoints of interest. RESULTS: Nineteen patients (73%) were above the age of 60 years; the median age was 70 years (range, 28-87 years). Most primary sites were in the Waldeyer's ring (15 patients, 60%), whereas in four patients (27%) only the palatine tonsil was affected. The SUV(max) ranged from 5.8 to 33.9. In one patient, relevant fluorodeoxyglucose (FDG) uptake within the intestine revealed a cecal adenocarcinoma as a secondary primary. Twenty of the 25 clinically followed patients (80%) achieved complete remission after treatment. Patients with high SUV(max) showed favorable survival (log-rank test, P = .044). A tendency for longer survival within the group with follow-up PET/CT studies could be noted but with no significant statistical difference (P = .349). CONCLUSIONS: (18)F-FDG-PET/CT imaging is a potent primary staging tool. It also has application as an instrument for evaluation of follow-up and response to therapy in patients suffering from primary extranodal lymphoma and for detection of secondary malignancies. Furthermore, (18)F-FDG uptake by the primary lesion may be related to better survival.

Objective: To integrate CT-perfusion into a routine, clinical contrast-enhanced (ce) PET/CT protocol for the evaluation of liver metastases and to compare functional CT and PET parameters. Materials and methods: Forty-six consecutive patients (mean age: 60 (34-82) years; 20 f, 26m) with known liver lesions (colorectal metastases (n=34), primary liver cancer (n=4), breast cancer (n=3), anal cancer, gastric cancer, esophageal cancer, GIST, duodenal cancer (all: n=1) who were referred for staging or therapy follow-up by [18F]-Fluoro-2-deoxy-D-glucose-positron-emission-tomography/computed-tomography imaging (FDG-PET/CT) were included. After acquisition of a low-dose PET/CT, a split-injection (70-90mL) ce-CT-protocol, including a 35-s CT-perfusion scan of the liver and a diagnostic ce-CT of the thorax and/or abdomen (70s delay, iv-contrast volume: 90mL, 4mL/s) was performed. CT-perfusion parameters (BF, BV, MTT,) and semi-quantitative PET-parameters (SUVmax, SUVmean, TLG, PETvol) were analyzed and compared. Results: CT-perfusion data could be obtained in all but one patient with shallow breathing. In all patients, diagnostic ce-PET/CT quality was adequate without the use of additional contrast media. Significant correlations (P

The purpose of the study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) during follow-up of patients with Hodgkin's lymphoma.Patients in complete remission or an unconfirmed complete remission after first-line therapy who received FDG-PET/CT during their follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in case of recurrence.Overall, 134 patients were analyzed. Forty-two (31.3%) patients had a recurrence. The positive predictive value of FDG-PET/CT was 0.98. Single-factor analysis identified morphological residual mass [P = 0.0005, hazard ratio (HR) 3.4, 95% confidence interval (CI) 1.7-6.6] and symptoms (P0.0001, HR 4.9, 95% CI 2.4-9.9) as significant risk factors for relapse. By multivariate analysis, morphological residual mass was the only significant risk factor for early follow-up (24 months) (P = 0.0019, HR 7.6, 95% CI 2.1-27.3). Advanced stage (P = 0.0426, HR 3.6, 95% CI 1.1-12.3) and the presence of symptoms (P = 0.0009, HR = 14.6, 95% CI 3.0-69.7) were found to be significant risk factors for later follow-up (24 months).Asymptomatic patients without morphological residues and an early stage of disease do not need a routine FDG-PET/CT for follow-up. Asymptomatic patients with morphological residues should receive routine follow-up FDG-PET/CT for the first 24 months. Only patients with advanced initial stage do need a routine follow-up FDG-PET/CT beyond 24 months.