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Am J Nucl Med Mol Imaging 2013;3(1):32-43

Original Article
A comparison of image contrast with 64Cu-labeled long
circulating liposomes and 18F-FDG in a murine model
of mammary carcinoma

Andrew W Wong, Eleanor Ormsby, Hua Zhang, Jai Woong Seo, Lisa M Mahakian, Charles F Caskey,
Katherine W Ferrara

Department of Biomedical Engineering, University of California, Davis, CA 95616, USA

Received September 18, 2012; Accepted November 13, 2012; Epub January 5, 2013; Published January 15,

Abstract: Conjugation of the 64Cu PET radioisotope (t1/2 = 12.7 hours) to long circulating liposomes enables long
term liposome tracking. To evaluate the potential clinical utility of this radiotracer in diagnosis and therapeutic guidance,
we compare image contrast, tumor volume, and biodistribution of 64Cu-liposomes to metrics obtained with the
dominant clinical tracer, 18F-FDG. Twenty four female FVB mice with MET1 mammary carcinoma tumor grafts were
examined. First, serial PET images were obtained with the 18F-FDG radiotracer at 0.5 hours after injection and with
the 64Cu-liposome radiotracer at 6, 18, 24, and 48 hours after injection (n = 8). Next, paired imaging and histology
were obtained at four time points: 0.5 hours after 18F-FDG injection and 6, 24, and 48 hours after 64Cu-liposome
injection (n = 16). Tissue biodistribution was assessed with gamma counting following necropsy and tumors were
paraffin embedded, sectioned, and stained with hematoxylin and eosin. The contrast ratio of images obtained using
18F-FDG was 0.88 ± 0.01 (0.5 hours after injection), whereas with the 64Cu-liposome radiotracer the contrast ratio
was 0.78 ± 0.01, 0.89 ± 0.01, 0.88 ± 0.01, and 0.94 ± 0.01 at 6, 18, 24, and 48 hours, respectively. Estimates
of tumor diameter were comparable between 64Cu-liposomes and 18F-FDG, 64Cu-liposomes and necropsy, and 64Culiposomes
and ultrasound with Pearson’s r-squared values of 0.79, 0.79, and 0.80, respectively. Heterogeneity of
tumor tracer uptake was observed with both tracers, correlating with regions of necrosis on histology. The average
tumor volume of 0.41 ± 0.05 cc measured with 64Cu-liposomes was larger than that estimated with 18F-FDG (0.28
± 0.04 cc), with this difference apparently resulting primarily from accumulation of the radiolabeled particles in the
pro-angiogenic tumor rim. The imaging of radiolabeled nanoparticles can facilitate tumor detection, identification of
tumor margins, therapeutic evaluation and interventional guidance. (ajnmmi1209002).

Keywords: 64Cu, 18F-FDG, liposomes, mammary carcinoma, PET, preclinical, biodistribution

Address all correspondence to:
Dr. Katherine W Ferrara
Department of Biomedical Engineering
University of California, Davis
451 Health Sciences
Drive, Davis, California 95616, USA.
Phone: (530) 7549436; Fax: (530) 7545739
E-mail: kwferrar@ucdavis.edu