Quantitative Liver Lesion Volume Determination by Nanoparticle-Based SPECT
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The aim of this paper is to present a simple and quantitative data analysis method with a new potential in the application of liver single-photon emission computed tomography (SPECT) imaging. We have established quantitative SPECT/computed tomography (CT) in vivo imaging protocols for determination of liver tumor burden based on the known role of Kupffer cells in cancer of the liver.
As it is also known that functional Kupffer cells accumulate particulate material contained in the arterial blood of liver supply, we used radiolabeled macro-aggregated albumin particles ([99mTc]-MAA) injected intravenously to image liver disease. Quantification of cold spot liver lesion imaging was also a general objective.
We examined a healthy control group (BALB/C mice, n = 6) and group of induced hepatocellular carcinoma (HCC, matrilin-2 transgenic KO mice, n = 9), where hepatocellular carcinoma was induced by diethylnitrosamine. We used [99mTc]-MAA as radiopharmaceutical for liver SPECT imaging in a small animal SPECT/CT system. A liver radioactivity overview map was generated. Segmentation of the liver was calculated by Otsu thresholding method. Based on the segmentation the radioactivity volume and the summarized liver activity were determined.
Tumor burden of the livers was quantitatively determined by creating parametric data from the resulting volumetric maps. Ex vivo liver mass data were applied for the validation of in vivo measurements. An uptake with cold spots as tumors was observed in all diseased animals in SPECT/CT scans. Isotope-labeled particle uptake (standardized uptake concentration) of control (median 0.33) and HCC (median 0.18) groups was significantly different (p = 0.0015, Mann Whitney U test).
A new potential application of [99mTc]-MAA was developed and presents a simple and very effective means to quantitatively characterize liver cold spot lesions resulting from Kupffer cell dysfunctions as a consequence of tumor burden.
Key wordsHepatocellular carcinoma (HCC) SPECT/CT Quantification Particle Macro-aggregated albumin Kupffer cell
The authors thank Dr. László Puskás and Ibolya Kiss for the animal models and Dr. Miklós Kellermayer for his support. The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. HEALTH-F2-2011-278850 (INMiND), from the grant of the Hungarian Government's National Research and Development Office (NKTH-“AVINOMID”). This research was conducted in the framework of a Master Research Agreement of Semmelweis University and Mediso, Ltd., and a Research Agreement of Basic Medical Sciences Centre, Semmelweis University, and CROmed, Ltd.
Conflict of Interest
The authors declare that they have no conflict of interest.
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