The effect of intra-arterial angiotensin II on the hepatic tumor to non-tumor blood flow ratio for radioembolization: a systematic review.
OBJECTIVE
Treatment efficacy of intra-arterial radioembolization for liver tumors depends on the selective targeting of tumorous tissue. Recent investigations have demonstrated that tumors may receive inadequate doses of radioactivity after radioembolization, due to unfavorable tumor to non-tumor (T/N) uptake ratios of radioactive microspheres. Hepatic arterial infusion of the vasoconstrictor angiotensin II (AT-II) is reported to increase the T/N blood flow ratio. The purpose of this systematic review was to provide a comprehensive overview of the effect of hepatic arterial AT-II on T/N blood flow ratio in patients with hepatic malignancies, and determine its clinical value for radioembolization.


METHODS
This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A structured search was performed in the PubMed, EMBASE and Cochrane databases. Only studies that presented data on T/N ratios before and after infusion of AT-II into the hepatic artery, in human patients with hepatic malignancies, were selected. Median T/N ratios before, during and after AT-II infusion, and the median T/N ratio improvement factor were extracted from the selected articles. All data on systemic blood pressure measurements and clinical symptoms were also extracted.


RESULTS
The search identified 524 titles of which 5 studies, including a total of 71 patients were considered relevant. Median T/N ratios before infusion of AT-II ranged from 0.4 to 3.4. All studies observed a substantial improvement of the T/N ratio after AT-II infusion, with median improvement factors ranging from 1.8 to 3.1. A transitory increase of systemic blood pressure was observed during AT-II infusion.


CONCLUSIONS
Infusion of AT-II into the hepatic artery leads to an increase of the tumor to non-tumor blood flow ratio, as measured by T/N uptake ratios. Clinical trials are warranted to assess safety aspects, optimal administration strategy and impact on treatment efficacy during radioembolization.
Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Andor F
AF
van den Hoven
Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Maarten L J
ML
Smits
Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Charlotte E N M
CE
Rosenbaum
Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Helena M
HM
Verkooijen
Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Maurice A A J
MA
van den Bosch
Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Marnix G E H
MG
Lam
D000804:Angiotensin II / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D004621:Embolization, Therapeutic / Q000009:adverse effects / Q000592:standards; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000098:blood supply* / Q000628:therapy*; D011868:Radioisotopes / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects
D011868:Radioisotopes; D000804:Angiotensin II