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Multimodal molecular 3D imaging for the tumoral volumetric distribution assessment of folate-based biosensors


The aim of this study was to characterize the in vivo volumetric distribution of three folate-based biosensors by different imaging modalities (X-ray, fluorescence, Cerenkov luminescence, and radioisotopic imaging) through the development of a tridimensional image reconstruction algorithm. The preclinical and multimodal Xtreme imaging system, with a Multimodal Animal Rotation System (MARS), was used to acquire bidimensional images, which were processed to obtain the tridimensional reconstruction. Images of mice at different times (biosensor distribution) were simultaneously obtained from the four imaging modalities. The filtered back projection and inverse Radon transformation were used as main image-processing techniques. The algorithm developed in Matlab was able to calculate the volumetric profiles of 99mTc-Folate-Bombesin (radioisotopic image), 177Lu-Folate-Bombesin (Cerenkov image), and FolateRSense™ 680 (fluorescence image) in tumors and kidneys of mice, and no significant differences were detected in the volumetric quantifications among measurement techniques. The imaging tridimensional reconstruction algorithm can be easily extrapolated to different 2D acquisition-type images. This characteristic flexibility of the algorithm developed in this study is a remarkable advantage in comparison to similar reconstruction methods.

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The authors are grateful for the support of the Mexican National Council of Science and Technology (CONACYT-SEP-CB-2014-01-242443 and CONACyT-PDCPN-2015-01-1040) and to the National Polytechnic Institute (IPN-SIPCOFAA-2015-0344). This research was carried out as part of the activities of the “Laboratorio Nacional de Investigación y Desarrollo de Radiofármacos, CONACyT.”

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Correspondence to Clara L. Santos-Cuevas.

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The study was approved by the Institutional Ethical Committee for the Care and Use of Laboratory Animals (“Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán”).

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Ramírez-Nava, G.J., Santos-Cuevas, C.L., Chairez, I. et al. Multimodal molecular 3D imaging for the tumoral volumetric distribution assessment of folate-based biosensors. Med Biol Eng Comput 56, 1135–1148 (2018).

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  • Tridimensional reconstruction
  • Inverse Radon transformation
  • In vivo imaging
  • Folate-based biosensors