First human study in treatment of unresectable liver metastases from colorectal cancer with irinotecan-loaded beads (DEBIRI)

The objective of this pilot clinical study was to assess the safety, technical feasibility, pharmacokinetic (PK) profile and tumour response of DC Bead™ with irinotecan (DEBIRI™) delivered by intra-arterial embolisation for the treatment of metastatic colorectal cancer. Eleven patients with unresectable liver metastases from CRC, tumour burden <30% of liver volume, adequate haematological, liver and renal function, performance status of <2 were included in this study. Patients received up to 4 sessions of TACE with DEBIRI at 3-week intervals. Feasibility of the procedure, safety and tumour response were assessed after each cycle. PK was measured after the first cycle. Patients were followed up to 24 weeks. Only mild to moderate adverse events were observed. DEBIRI is a technically feasibile procedure; no technical complications were observed. Average Cmax for irinotecan and SN-38 was 194 ng/ml and 16.7 ng/ml, respectively, with average t½ of 4.6 h and 12.4 h following administration of DEBIRI. Best overall response during the study showed disease control in 9 patients (2 patients with partial response and 7 with stable disease, overall response rate of 18%). Our study shows that transarterial chemoembolisation with irinotecan-loaded DC beads (DEBIRI) is safe, technically feasible and effective with a good PK profile

Gadobutrol in Renally Impaired Patients: Results of the GRIP Study.

OBJECTIVE: The aim of this study was to assess the potential risk of gadobutrol-enhanced magnetic resonance imaging (MRI) in patients with moderate to severe renal impairment for the development of nephrogenic systemic fibrosis (NSF). MATERIALS AND METHODS: We performed a prospective, international, multicenter, open-label study in 55 centers. Patients with moderate to severe renal impairment scheduled for any gadobutrol-enhanced MRI were included. All patients received a single intravenous bolus injection of gadobutrol at a dose of 0.1 mmol/kg body weight. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. RESULTS: A total of 908 patients were enrolled, including 586 with moderate and 284 with severe renal impairment who are at highest risk for developing NSF. The mean time since renal disease diagnosis was 1.83 and 5.49 years in the moderate and severe renal impairment cohort, respectively. Overall, 184 patients (20.3%) underwent further contrast-enhanced MRI with other gadolinium-based contrast agents within the 2-year follow-up. No patient developed symptoms conclusive of NSF. CONCLUSIONS: No safety concerns with gadobutrol in patients with moderate to severe renal impairment were identified. There were no NSF cases

Comparison of 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine-enhanced MRI in 471 patients with known or suspected renal lesions: Results of a multicenter, single-blind, interindividual, randomized clinical phase III trial

The purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, interindividual, randomized study design, both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy, sensitivity, and specificity to correctly classify focal lesions of the kidney. To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading. The average diagnostic accuracy across the three blinded readers ('average reader') was 83.7% for gadobutrol and 87.3% for gadopentate dimeglumine. The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0% for gadobutrol and 6.9% for gadopentate dimeglumine. Sensitivity of the average reader was 85.2% for gadobutrol and 88.7% for gadopentate dimeglumine. Specificity of the average reader was 82.1% for gadobutrol and 86.1% for gadopentate dimeglumine. In conclusion, this study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI

Magnetresonanztomographie der Leber : Evaluation des neuen hepatobiliären, leberspezifischen Kontrastmittels Gd-EOB-DTPA für die Detektion und Charakterisierung von fokalen Leberläsionen

In den letzten Jahren hat eine rasante Entwicklung der Gerätetechnik sowohl der CT als auch der MRT stattgefunden und eine Änderung der Untersuchungsverfahren im Bereich der Schnittbildtechnik ausgelöst. Parallel dazu sind durch die Einführung von MRT-Kontrastmitteln neuartige Untersuchungsprotokolle entstanden. Deshalb muß eine ständige Reevaluierung der einzelnen Untersuchungsverfahren erfolgen. Organ- bzw. gewebespezifische Kontrastmittel sind den extrazellulären nicht-spezifi-schen MRT-Kontrastmitteln nicht gleichzusetzen. Mit dem neu entwickelten Kontrast-mittel Gd-EOB-DTPA steht für die MRT ein neues leberspezifisches KM zur Verfü-gung, welches in Kürze in routinemäßige Untersuchungen übergehen wird. Es ermöglicht die sichere Unterscheidung von lebereigenem bzw. hepatozyten-reichem Gewebe durch eine direkte Aufnahme des Kontrastmittels in die Leberzelle selbst. Maligne Lebertumoren, wie z. B. Metastasen, die keine Hepatozyten besitzen, zeigen keine Speicherung der hepatobiliären, leberspezifischen Substanz. Bis zum heutigen Tage sind die Erfahrungen mit diesem neuen Kontrastmittel gering. Aus diesem Grund sollten im Rahmen einer prospektiven Zulassungsstudie Erfahrungen mit der neuartigen Substanz gesammelt werden. Insgesamt wurden 60 Patienten in die beschriebene Studie eingeschlossen. Bei allen Patienten wurde eine nicht-kontrastverstärkte MRT, eine kontrastverstärkte MRT mit Gd-EOB-DTPA als auch eine Spiral-CT der Leber erstellt. In der vorliegenden Studie wurde sowohl die Detektion als auch die Charakterisierung in Korrelation mit einem genau definierten Referenzstandard evaluiert. Die Ergebnisse der vorgestellten Studie indizieren, daß es sich bei Gd-EOB-DTPA um ein sicheres, nebenwirkungarmes Kontrastmittel für die MRT handelt. Das besondere an diesem neuartigen Kontrastmittel ist, daß mit einer intravenösen Appli-kation unterschiedliche Perfusionsphasen dargestellt werden können. Im einzelnen handelt es sich um die intravasale Phase zur Darstellung der Vaskularität, die Parenchym- oder hepatobiliären Phase zur Detektion und Charakterisierung, sowie die Ausscheidungsphase zur Darstellung der Gallengänge. Die sichere intravenöse Bolusgabe des hepatobiliären Kontrastmittels ermöglicht zum einen dynamische Perfusionsbildgebung, zum anderen aber auch statische leberspezifische Hepa-tozytenbildgebung und damit funktionelle Leberbildgebung. Die MRT unter Verwendung des neuen Kontrastmittels Gd-EOB-DTPA stellt eine adäquate diagnostische Methode für die Detektion, Lokalisierung, exakte Abgren-zung und Charakterisierung von fokalen Leberläsionen dar, die der nicht-kontrast-verstärkten MRT und der Spiral-CT überlegen ist. Die Detektionsrate ist verbessert gegenüber der biphasischen Spiral-CT mit einer gering höheren Rate von detektierten kleinen Läsionen. Zusätzliche Informationen bezüglich der Ätiologie werden sowohl durch dynamische als auch statische MRT-Bildgebung für die Klassifizierung von malignen versus benignen Leberläsionen als auch für die Charakterisierung nach Läsionstyp erhoben. Anhand der durchgeführten Untersuchungen konnte ein Verhaltensmuster der unterschiedlichen Pathologien für dieses neue Kontrastmittel dargestellt werden. Metastasen weisen je nach ihrem Vaskularisationsgrad eine unterschiedliche An-reicherung in der Perfusionsphase auf, während sie in der hepatobiliären Phase als Kontrastmittelaussparung zur Darstellung kommen. Lebereigene Läsionen wie die FNH besitzen Hepatozyten, nehmen das leberspezifische Kontrastmittel auf, sind vergleichbar mit normalen Lebergewebe und lassen sich gut von leberfremden Ge-webe abgrenzen. Die hepatozellulären Karzinome zeigen in Frühphase eine deut-liche meist in der Peripherie gelegene Hyperperfusion. In der hepatobiliären Phase ist die KM-Aufnahme abhängig vom Differenzierungsgrad. Undifferenzierte HCCs verhalten sich wie leberfremdes Gewebe und nehmen kein KM auf, während beim gut differenzierten HCC eine diskrete Aufnahme gefunden werden kann. Die hohe Sensitivität bezüglich Detektion aber auch eine hervorragende Klassifi-zierung und Charakterisierung ermöglichen eine gezielte und genaue weitere Pla-nung der Therapie der Patienten. Mittels EOB-MRT ist eine präzise Diagnose des Leberparenchyms mit Hepatozytenfunktion als auch Perfusionsstudien in einem Untersuchungsgang möglich. Die Bildgebung der Hepatozytenphase kann 20 Minuten nach Injektion des hepatobiliären Kontrastmittels erstellt werden und ermöglicht damit eine Zeitersparnis und Kostenreduzierung im Vergleich zu den anderen hepatobiliären Kontrastmitteln. In der täglichen Routine, das prätherapeutischen Management von Patienten bei fokalen Leberläsionen betreffend, sollte nach den vorliegenden Ergebnissen eine leberspezifische MRT durchgeführt werden.The last years have seen dramatic changes in the technical development of modalities regarding CT and MRI and have resulted in several changes in cross-sectional examination technique. Due to the development of contrast agents, sequence protocols have been redesigned. Therefore, an ongoing reevaluation of the different examination techniques has to be performed. Organ- and tissue-specific contrast agents cannot be compared to non-specific extracellular MRI contrast agents. The newly developed contrast agent Gd-EOB-DTPA can be used in MRI as a new liver-specific contrast medium, which will soon be available in daily clinical routine. Thus, a precise differentiation between liver tissue and hepatocytic tissue becomes possible due to a direct uptake of the contrast agent in the liver cell itself. Malignant liver tumors, such as metastases, do not contain any hepatocytes and show no uptake of the hepatobiliary, liver-specific substance. Until today little is known about this new contrast agent. Therefore a prospective study for approval was performed to obtain more information on this new substance. 60 patients were included in the study. All patients underwent unenhanced MRI, contrast-enhanced MRI using Gd-EOB-DTPA and spiral CT of the liver. Detection as well as characterization were evaluated in correlation to a well defined standard of reference. The results of the present study document that Gd-EOB-DTPA is a safe and well-tolerated contrast agent for MRI. The principle of this new contrast medium is to perform different perfusion phases with one intravenous administration. The intra-vascular phase is performed to provide information on vascularity, the parenchymal or hepatobiliary phase for detection and characterization and the distribution phase to visualize the biliary system. The safe intravenous bolus administration of the hepatobiliary contrast agent enables on the one hand dynamic perfusion imaging, on the other hand static liver-specific hepatocyte imaging and thus functional liver imaging. The use of the new contrast agent Gd-EOB-DTPA for MRI is an adequate diagnostic method for the detection, localisation, precise delineation and characterization of focal liver lesions. It is superior to unenhanced MRI and spiral CT. The detection rate is increased compared to bi-phasic spiral CT with a slightly higher rate of depicted small lesions. Additional information regarding etiology is obtained using dynamic as well as static MR imaging for the classification of malignant versus benign liver lesions and for the characterization according to lesion type. In this study enhancement patterns of various pathologies were presented using this new contrast agent. Metastases show different enhancement behaviors according to their vascularity in the perfusion phase, whereas almost no uptake of contrast material is depicted in the hepatobiliary phase. Liver tissue and hepatocytic tissue such as the FNH contain hepatocytes therefore demonstrating contrast medium enhancement comparable to normal liver tissue and can be differentiated from non-liver tissue. Hepatocellular carcinomas show a peripheral hypervascularity in the early phase. In the hepatobiliary phase contrast media uptake depends on the grading. Undifferentiated HCC reacts like non-liver tissue and shows no uptake of contrast medium, whereas the highly differentiated HCC is seen with a moderate enhancement. A high sensitivity concerning detection as well as an excellent classification and characterization provides an adequate management of therapy in patients. Using EOB-MRI a precise diagnosis of liver parenchyma regarding function of hepatocytes as well as perfusion studies can be obtained as an all-in-one method. Imaging in the hepatobiliary phase is obtained 20 minutes post administration of the hepatobiliary contrast medium and is therefore less time-consuming and helps to reduce costs compared to other hepatobiliary contrast agents. Concerning the pre-therapeutic management of patients suffering from focal liver lesions a liver-specific MRI should be performed in the daily clinical routine according to the data of the present study

Lipiodol as a Predictive Indicator for Therapy Response to Transarterial Chemoembolization of Hepatocellular Carcinoma

Background: To evaluate the predictive value of Lipiodol for response evaluation of hepatocellular carcinoma (HCC) treated with conventional transarterial chemoembolization (cTACE) by analysis of the enhancement pattern during angiography and in postinterventional computed tomography (CT). Materials and Methods: This retrospective study included 30 patients (mean age 63 years, range: 36 to 82 years, 22 males) with HCC. Patients received three Lipiodol-based cTACE sessions, each followed by an unenhanced CT within 24-h. Contrast-enhanced magnetic resonance imaging (MRI) was acquired before and after the treatment to determine tumor response. Lipiodol enhancement pattern, tumor vascularization, and density were evaluated by angiography and CT. Initial tumor size and response to cTACE were analyzed by MRI according to modified response evaluation criteria in solid tumors (mRECIST) in a 4-week follow-up. Results: Analysis of HCC lesions (68 lesions in 30 patients) during cTACE revealed clear visibility and hypervascularization in angiography as a potential independent parameter able to predict tumor response. A significant correlation was found for response measurements by volume (p = 0.012), diameter (p = 0.006), and according to mRECIST (p = 0.039). The amount of Lipiodol and enhancement pattern in postinterventional CT did not correlate with therapy response. Measurements of Hounsfield unit values after cTACE do not allow sufficient prediction of the tumor response. Conclusion: Hypervascularized HCC lesions with clear visibility after Lipiodol administration in the angiography respond significantly better to cTACE compared to hypo- or nonvascularized lesions

CT-guided biopsies of unspecified suspect intrahepatic lesions: pre-procedure Lipiodol-marking improves the biopsy success rate

While computed tomography (CT)-guided liver biopsies are commonly performed using unenhanced images, contrast-enhanced images are beneficial for challenging puncture pathways and lesion locations. This study aimed to evaluate the accuracy of CT-guided biopsies for intrahepatic lesions using unenhanced, intravenous (IV)-enhanced, or intra-arterial Lipiodol-marked CT for lesion marking