Negative contrast Cerenkov luminescence imaging of blood vessels in a tumor mouse model using [68Ga]gallium chloride

Abstract

BackgroundCerenkov luminescence imaging (CLI) is an emerging imaging technique where visible light emitted from injected beta-emitting radionuclides is detected with an optical imaging device. CLI research has mostly been focused on positive contrast imaging for ascertaining the distribution of the radiotracer in a way similar to other nuclear medicine techniques. Rather than using the conventional technique of measuring radiotracer distribution, we present a new approach of negative contrast imaging, where blood vessel attenuation of Cerenkov light emitted by [68Ga]GaCl3 is used to image vasculature.MethodsBALB/c nude mice were injected subcutaneously in the right flank with HT-1080 fibrosarcoma cells 14 to 21 days prior to imaging. On the imaging day, [68Ga]GaCl3 was injected and the mice were imaged from 45 to 90 min after injection using an IVIS Spectrum in vivo imaging system. The mice were imaged one at a time, and manual focus was used to bring the skin into focus. The smallest view with pixel size around 83 μm was used to achieve a sufficiently high image resolution for blood vessel imaging.ResultsThe blood vessels in the tumor were clearly visible, attenuating 7% to 18% of the light. Non-tumor side blood vessels had significantly reduced attenuation of 2% to 4%. The difference between the attenuation of light of tumor vessels (10% ± 4%) and the non-tumor vessels (3% ± 1%) was significant. Moreover, a necrotic core confirmed by histology was clearly visible in one of the tumors with a 21% reduction in radiance.ConclusionsThe negative contrast CLI technique is capable of imaging vasculature using [68Ga]GaCl3. Since blood vessels smaller than 50 μm in diameter could be imaged, CLI is able to image structures that conventional nuclear medicine techniques cannot. Thus, the negative contrast imaging technique shows the feasibility of using CLI to perform angiography on superficial blood vessels, demonstrating an advantage over conventional nuclear medicine techniques.

Cerenkov luminescence imaging: physics principles and potential applications in biomedical sciences

“…Other preclinical CLI applications Potential uses of preclinical CLI which have been evaluated are also intraoperative imaging of radionuclides [109], surgical resection [110], endoscopic imaging for intraoperative surgical navigation [111], study of gene expression [57, 112–114], dynamic imaging [115], interscapular brown adipose tissue visualization [116], quantitive tissue oxygenation assessment [117], and negative contrast imaging of blood vessel attenuation of Cerenkov light to image vasculature [55]. In [118], Cerenkov-specific contrast agents for pH detection have been developed, while in [119] antibody-based PET radiotracers have been evaluated via CLI.…”

Continued rapid growth in 68Ga applications: update 2013 to June 2014

“…Cerenkov luminescence imaging (CLI) detecting visible light emitted by positron emitting radionuclides was found relevant for the visualization of vasculature . This technique allowed high‐contrast imaging of as small as 50 µm (in diameter) blood vessels in mice with fibrosarcoma tumour using [ 68 Ga]GaCl 3 , thus demonstrating potential for the development of CLI for angiography of subcutaneous blood vessels.…”

Enhanced Cerenkov luminescence tomography analysis based on Y2O3:Eu3+ rare earth oxide nanoparticles

“…Several notable studies, for instance, have been able to use CLI to image clearly things like the accumulation of 131 I in thyroid diseases and the uptake of 18 F-FDG in lymphatic nodes in axillary regions [8][9][10]. However, although CLI has been applied in a few preclinical and clinical studies, its applications remain limited because of its low intensity and the poor penetration of Cerenkov luminescence (CL), which is mainly distributed in the ultraviolet and blue bands (300-520 nm), leading to mass absorption and scattering in biological tissues [11,12]. Poor imaging quality has added to the difficulty of bringing about effective Cerenkov luminescence tomography (CLT) [2].…”