In Vivo 3-Dimensional Radiopharmaceutical-Excited Fluorescence Tomography

J Nucl Med. 2017 Jan;58(1):169-174. doi: 10.2967/jnumed.116.180596. Epub 2016 Sep 22.

Abstract

Cerenkov luminescence imaging can image radiopharmaceuticals using a high-sensitivity charge-coupled device camera. However, Cerenkov luminescence emitted from the radiopharmaceuticals is weak and has low penetration depth in biologic tissues, which severely limits the sensitivity and accuracy of Cerenkov luminescence imaging. This study presents 3-dimensional (3D) radiopharmaceutical-excited fluorescence tomography (REFT) using europium oxide (EO) nanoparticles, which enhances the Cerenkov luminescence signal intensity, improves the penetration depth, and obtains more accurate 3D distribution of radiopharmaceuticals.

Methods: The enhanced optical signals of various radiopharmaceuticals (including Na131I, 18F-FDG, 68GaCl3, Na99mTcO4) by EO nanoparticles were detected in vitro. The location and 3D distribution of the radiopharmaceuticals of REFT were then reconstructed and compared with those of Cerenkov luminescence tomography through the experiments with the phantom, artificial source-implanted mouse models, and mice bearing hepatocellular carcinomas.

Results: The mixture of 68GaCl3 and EO nanoparticles possessed the strongest optical signals compared with the other mixtures. The in vitro phantom and implanted mouse studies showed that REFT revealed more accurate 3D distribution of 68GaCl3 REFT can detect more tumors than small-animal PET in hepatocellular carcinoma-bearing mice and achieved more accurate 3D distribution information than Cerenkov luminescence tomography.

Conclusion: REFT with EO nanoparticles significantly improves accuracy of localization of radiopharmaceuticals and can precisely localize the tumor in vivo.

Keywords: Cerenkov luminescence imaging (CLI); PET; hepatocellular carcinoma (HCC); radionuclides; radiopharmaceutical excitation fluorescence tomography (REFT).

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / chemistry
  • Carcinoma, Hepatocellular / diagnostic imaging*
  • Cell Line, Tumor
  • Image Enhancement / methods
  • Imaging, Three-Dimensional / methods*
  • Male
  • Metal Nanoparticles / analysis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Fluorescence / instrumentation
  • Microscopy, Fluorescence / methods*
  • Molecular Imaging / instrumentation
  • Molecular Imaging / methods*
  • Phantoms, Imaging
  • Positron-Emission Tomography / instrumentation
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / analysis*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tomography, Optical / instrumentation
  • Tomography, Optical / methods
  • Whole Body Imaging / instrumentation
  • Whole Body Imaging / methods

Substances

  • Radiopharmaceuticals