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Improved Derivation of Input Function in Dynamic Mouse [18F]FDG PET Using Bladder Radioactivity Kinetics

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Abstract

Purpose

Accurate determination of the plasma input function (IF) is essential for absolute quantification of physiological parameters in positron emission tomography (PET). However, it requires an invasive and tedious procedure of arterial blood sampling that is challenging in mice because of the limited blood volume. In this study, a hybrid modeling approach is proposed to estimate the plasma IF of 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) in mice using accumulated radioactivity in urinary bladder together with a single late-time blood sample measurement.

Methods

Dynamic PET scans were performed on nine isoflurane-anesthetized male C57BL/6 mice after a bolus injection of [18F]FDG at the lateral caudal vein. During a 60- or 90-min scan, serial blood samples were taken from the femoral artery. Image data were reconstructed using filtered backprojection with computed tomography-based attenuation correction. Total accumulated radioactivity in the urinary bladder at late times was fitted to a renal compartmental model with the last blood sample and a one-exponential function that described the [18F]FDG clearance in blood. Multiple late-time blood sample estimates were calculated by the blood [18F]FDG clearance equation. A sum of four-exponentials was assumed for the plasma IF that served as a forcing function to all tissues. The estimated plasma IF was obtained by simultaneously fitting the [18F]FDG model to the time–activity curves (TACs) of liver and muscle and the forcing function to early (0–1 min) left-ventricle data (corrected for delay, dispersion, partial-volume effects, and erythrocyte uptake) and the late-time blood estimates. Using only the blood sample collected at the end of the study to estimate the IF and the use of liver TAC as an alternative IF were also investigated.

Results

The area under the plasma IFs calculated for all studies using the hybrid approach was not significantly different from that using all blood samples. [18F]FDG uptake constants in brain, myocardium, skeletal muscle, and liver computed by the Patlak analysis using estimated and measured plasma IFs were in excellent agreement (slope ∼ 1; R 2 > 0.983). The IF estimated using only the last blood sample drawn at the end of the study and the use of liver TAC as the plasma IF provided less reliable results.

Conclusions

The estimated plasma IFs obtained with the hybrid method agreed well with those derived from arterial blood sampling. Importantly, the proposed method obviates the need of arterial catheterization, making it possible to perform repeated dynamic [18F]FDG PET studies on the same animal. Liver TAC is unsuitable as an input function for absolute quantification of [18F]FDG PET data.

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Acknowledgments

This work was supported by National Institutes of Health (NIH) grants R01-EB001943 and P50-CA086306. Portions of this work were presented at the IEEE Medical Imaging Conference, Dresden, Germany, October 22–25, 2008 and the 56th Annual Meeting of the Society of Nuclear Medicine, Toronto, Canada, June 13–17, 2009. The authors would like to thank Waldemar Ladno, Judy Edwards, Antonia Luu, and David Stout for technical assistance in small-animal PET and CT imaging; Weber Shao, Dat Vu, and David Truong for computer and database support; and the UCLA Cyclotron staff for help with [18F]FDG preparation.

Conflict of Interest Disclosure

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA

    Koon-Pong Wong, Xiaoli Zhang & Sung-Cheng Huang

  2. Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA

    Sung-Cheng Huang

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  1. Koon-Pong Wong
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  2. Xiaoli Zhang
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Correspondence to Koon-Pong Wong.

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Wong, KP., Zhang, X. & Huang, SC. Improved Derivation of Input Function in Dynamic Mouse [18F]FDG PET Using Bladder Radioactivity Kinetics. Mol Imaging Biol 15, 486–496 (2013). https://doi.org/10.1007/s11307-013-0610-6

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