Intraprocedural 3D perfusion measurement during chemoembolisation with doxorubicin-eluting beads in liver metastases of malignant melanoma.

OBJECTIVES: To study feasibility and validity of a new software application for intraprocedural assessment of perfusion during chemoembolisation of melanoma metastases. METHODOLOGY: In a prospective phase-II trial, ten melanoma patients with liver-only metastases underwent chemoembolisation with doxorubicin-eluting beads (DEBDOX-TACE). Tumour perfusion was evaluated immediately before and after treatment at cone beam computer tomography (CBCT) using a new software application. For control and comparison, patients underwent perfusion measurement via contrast-enhanced multidetector CT (MDCT) before and after treatment. RESULTS: CBCT showed 94.7 % reduction in perfusion in metastases after DEBDOX-TACE, whereas MDCT showed 96.8 %. Reduction in perfusion after treatment was statistically significant (p < 0.01) for both methods. The additional time needed for data acquisition during treatment was 5 min per case or less; the post-processing data analysis was 10 min or less. Perfusion imaging was associated with additional contrast agent and patient exposure to radiation (dose-length product [DLP]): 18 ml and 394 mGy*cm in CBCT and 100 ml and 446 mGy*cm in MDCT, respectively. CONCLUSIONS: Reduction in perfusion of melanoma metastases after DEBDOX-TACE can be reliably assessed during the intervention via perfusion software at CBCT. Data acquisition and analysis require additional time but can be easily performed during the treatment. KEY POINTS: • Tumour perfusion of melanoma metastases can be assessed at cone beam CT. • The software shows a significant decrease of tumour perfusion after DEBDOX-TACE. • Data acquisition and analysis require an acceptable additional time during the procedure. • CBCT requires less radiation exposure and contrast for perfusion study than MSCT. • This software can monitor the course of DEBDOX-TACE in melanoma metastases.

Inhibition of cardiac Kir2.1-2.3 channels by beta3 adrenoreceptor antagonist SR 59230A.

Kir2.x channels form the molecular basis of cardiac I(K1) current and play a major role in cardiac electrophysiology. However, there is a substantial lack of selective Kir2 antagonists. We found the ß(3)-adrenoceptor antagonist SR59230A to be an inhibitor of Kir2.x channels. Therefore, we characterized the effects of SR59230A on Kir2.x and other relevant cardiac potassium channels. Cloned channels were expressed in the Xenopus oocyte expression system and measured with the double-microelectrode voltage clamp technique. SR59230A inhibited homomeric Kir2.1 channels with an IC(50) of 33µM. Homomeric Kir2.2 and Kir2.3 channels and Kir2.x heteromers were also inhibited by SR59230A with similar potency. In contrast, no relevant inhibitory effects of SR59230A were found in cardiac Kv1.5, Kv4.3 and KvLQT1/minK channels. In hERG channels, SR59230A only induced a weak inhibition at a high concentration. These findings establish SR59230A as a novel inhibitor of Kir2.1-2.3 channels with a favorable profile with respect to additional effects on other cardiac repolarizing potassium channels.