HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jnumed.106.039180v1 48/7/1216    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JNM Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Peñuelas, I. Articles by Prósper, F. Search for Related Content PubMed PubMed Citation Articles by Peñuelas, I. Articles by Prósper, F.

¹³N-Ammonia PET as a Measurement of Hindlimb Perfusion in a Mouse Model of Peripheral Artery Occlusive Disease

¹ Department of Nuclear Medicine, Clínica Universitaria, University of Navarra, Pamplona, Spain; ² MicroPET Research Unit CIMA-CUN, University of Navarra, Pamplona, Spain; ³ Hematology and Cell Therapy Service, Clínica Universitaria, University of Navarra, Pamplona, Spain; and ⁴ Foundation for Applied Medical Research (FIMA), University of Navarra, Pamplona, Spain

Correspondence: For correspondence or reprints contact: Iván Peñuelas, PhD, Department of Nuclear Medicine, Clínica Universitaria, Avda. Pío XII 36, 31008 Pamplona, Spain. E-mail: ipenuelas{at}unav.es

Peripheral arterial occlusive disease (PAOD) is a leading cause of mortality and morbidity in the western world. The development of noninvasive methods for assessment and comparison of the efficacy of novel therapies in animal models is of great importance. Methods: Hindlimb ischemia was induced in nude mice by ligation and excision of the left femoral artery (n = 5) or the left iliac artery (n = 10). Assessment of limb perfusion was performed by small-animal PET analysis after intravenous injection of ¹³N-ammonia between 24 h and 30 d after surgery using the ratio of perfusion between the left limb (ischemic) and the right limb (control). Activity concentration per area unit was calculated in regions of interest placed on 1-mm-thick images for numeric calculations, and the iliac and the femoral models were compared. In addition, histopathologic studies were performed to assess the degree of necrosis (hematoxylin–eosin) and fibrosis (sirius red). Immunohistochemistry analyses for identification of arterioles (-smooth muscle actin) and endothelium—capillaries—(Bandeiraea simplicifolia I [BS-I] lectin) were also performed. Results: Perfusion in both hindlimbs of control animals was similar (median of the left-to-right ratio = 0.99). Twenty-four hours after ischemia, perfusion of the ischemic limb (% mean ± SD) was 33.3 ± 10.6 and 22.1 ± 9.9 in the femoral and iliac models, respectively. Spontaneous recovery of perfusion in the hindlimb that underwent surgery was significantly lower in the iliac model at day +15 (73.2 ± 15.5 vs. 51.9 ± 11.3; P < 0.01). Fibrosis increased progressively until day +30, whereas muscle necrosis was maximal at day +7 with a moderate reduction by day +30. In accordance with this positive effect, there was a statistically significant increase in the area covered with smooth muscle-coated vessels (arterioles) at day +30 in comparison with day 7 (P < 0.05). In addition, a correlation between ¹³N-ammonia uptake and the amount of necrosis (r = –0.73; P = 0.06) and fibrosis (r = –0.67; P = 0.05) at day +30 was found. Conclusion: ¹³N-Ammonia imaging allows semiquantitative evaluation of hindlimb perfusion in surgical mouse models of acute hindlimb ischemia. Although spontaneous perfusion recovery is observed in both models, the iliac model shows a substantially lower recovery and is hence better suited for assessment of new therapeutic strategies for acute hindlimb ischemic disease.

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

Related articles in JNM:

This Month in JNM

JNM 2007 48: 11a-12a. [Full Text]