Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment
Cherenkov radiation imaging of beta emitters: in vitro and in vivo results
Introduction
The emission of Cherenkov radiation (CR) is a well-known phenomenon that takes place when charged particles travel through an optical transparent medium with a velocity greater than light velocity in the material. The CR emission is mostly in the visible range and, thus, CR photons can be detected by optical imaging techniques.
Quite recently our group [1] and Robertson et al. [2] have established a novel molecular imaging approach called Cherenkov luminescence imaging (CLI) for the in vivo imaging of small animals such as mice. CLI is based on the detection of CR generated by beta particles (both electrons or positrons) as they travel into the animal tissues with an energy such that Cherenkov emission condition is satisfied. More details on the theory behind CLI can be found in Ref. [1]. It is interesting to notice that even if CLI is a quite young molecular imaging tool, in the past six months some papers from independent research groups based on the use of CLI performed with several beta emitters has appeared in the literature [3], [4].
In order to perform a preliminary comparison between positron emission tomography (PET) with CLI we carried out an in vivo study using a xenograft tumor model of mammary carcinoma (BB1 tumor cells). More precisely we have investigated FDG tumor uptake using both PET and CLI dynamic imaging [5].
In this paper we review some of our previous results [1], [5] and we present novel in vitro data obtained using 32P. Such isotope is quite interesting from both a physical and biological point of view since 32P emits quite high energy electrons (1.7 MeV maximum energy) and has been heavily used for several biological applications.
The high energy of the emitted particles is an extremely useful characteristic since the number of emitted Cherenkov light photons depends on the particle energy, more precisely the higher the energy, the greater the number of emitted Cherenkov photons.
One of the most limiting characteristic of optical imaging is that optical photons scatter several times before escaping the animal surface and this limits the spatial resolution of the technique. In the case of CLI the particle range might also be a further cause of spatial resolution reduction. However, it is important to underline here that the Cherenkov light emission takes place not along the entire particle range but only in a limited portion of it, more precisely only in a region when the Cherenkov emission condition is fulfilled.
The paper is organized as follows: in Section 2 the experimental methods for CLI acquisition are briefly described and in Section 3 the main in vivo and in vitro results are presented. In particular, attention was focused on a comparison between the average radiance with respect to the activity measured using a conventional beta counter. The Cherenkov radiation spectra obtained with 18F and 32P were also compared. An example of FDG tumor uptake in a mouse was presented, conclusions then follow.
Section snippets
CLI acquisition
Cherenkov luminescence images were acquired by the IVIS 200 Vivo Vision System (Xenogen Corp., Alameda, USA) imager typically used for in vivo small animal imaging. In order to detect CR photons the IVIS 200 was used only in bioluminescence mode and, thus, without using any excitation lamps. The system is composed of a back-thinned, back-illuminated CCD camera, several filters (see next section for more details) and lens.
The instrument is based on a CCD detector consisting of a matrix of
In vitro results
Fig. 1 shows that the measured optical average radiance is well in agreement with the tracer activity measured using a conventional approach. This suggests that CLI allows to obtain quantitative measurements of tracer activity. A comparison between the CR spectra for both 18F and 32P solutions is presented in Fig. 2. As one can see there is good linear relationship between the two spectra and this matches fairly well with the model described in Ref. [1]. As expected the main difference between
Conclusions
The results presented in this paper showed that CLI is a novel molecular imaging method and can be used to image both β− and β+ emitters using conventional optical imaging devices for in vitro or in vivo studies.
We believe that such novel imaging methodology will open new and interesting research scenarios especially for the in vivo testing of novel radiopharmaceuticals labelled with pure β− isotopes, such as 90Y. Moreover, CLI technique could be improved by developing new devices for 3D image
Acknowledgments
The authors would like to acknowledge the Cariverona foundation for the financial support.
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