U-SPECT-BioFluo: an integrated radionuclide, bioluminescence, and fluorescence imaging platform

Abstract

BackgroundIn vivo bioluminescence, fluorescence, and single-photon emission computed tomography (SPECT) imaging provide complementary information about biological processes. However, to date these signatures are evaluated separately on individual preclinical systems. In this paper, we introduce a fully integrated bioluminescence-fluorescence-SPECT platform. Next to an optimization in logistics and image fusion, this integration can help improve understanding of the optical imaging (OI) results.MethodsAn OI module was developed for a preclinical SPECT system (U-SPECT, MILabs, Utrecht, the Netherlands). The applicability of the module for bioluminescence and fluorescence imaging was evaluated in both a phantom and in an in vivo setting using mice implanted with a 4 T1-luc + tumor. A combination of a fluorescent dye and radioactive moiety was used to directly relate the optical images of the module to the SPECT findings. Bioluminescence imaging (BLI) was compared to the localization of the fluorescence signal in the tumors.ResultsBoth the phantom and in vivo mouse studies showed that superficial fluorescence signals could be imaged accurately. The SPECT and bioluminescence images could be used to place the fluorescence findings in perspective, e.g. by showing tracer accumulation in non-target organs such as the liver and kidneys (SPECT) and giving a semi-quantitative read-out for tumor spread (bioluminescence).ConclusionsWe developed a fully integrated multimodal platform that provides complementary registered imaging of bioluminescent, fluorescent, and SPECT signatures in a single scanning session with a single dose of anesthesia. In our view, integration of these modalities helps to improve data interpretation of optical findings in relation to radionuclide images.

Tracers for Fluorescence-Guided Surgery: How Elongation of the Polymethine Chain in Cyanine Dyes Alters the Pharmacokinetics of a Dual-Modality c[RGDyK] Tracer

“…Determination of photophysical properties and of stability (18,27,36,38), receptor affinity (15), and fluorescence confocal imaging (15) was performed as previously described. The 4T1 tumor model was generated as previously described (15,18,39). All animal experiments were in accordance with Dutch welfare regulations and were approved by the local ethics committee of the Leiden University Medical Center.…”

“…, and DTPA-Cy7-(SO 3 ) methyl-COOH-c[RGDyK] with 111 InCl 3 and subsequent assessment of labeling accuracy was performed as described previously (18), using about 1 MBq for biodistribution (n 5 4) and 10-20 MBq for SPECT imaging (n 5 2), followed by ex vivo evaluation of the biodistribution (in total, 6 animals per tracer). Imaging of 4T1 tumor-bearing mice was performed on a U-SPECT scanner (MILabs) according to previously described methods (18,39).…”

Evaluation of a Fluorescent and Radiolabeled Hybrid Somatostatin Analog In Vitro and in Mice Bearing H69 Neuroendocrine Xenografts

“…However, photon attenuation limits tissue penetration to less than 1 cm (12); therefore, deep lesions cannot be identified based on fluorescence signal alone (10,13,14).…”

Development of an embedded multimodality imaging platform for onco-pharmacology using a smart anticancer prodrug as an example

“…Combinations of US with NIRF 25,26 , US/PA with NIRF 6,[27][28][29] , or of US with MRI and BLI 30 , have also been investigated. Some combinations with radioactive modalities are also described in the literature, such as PET with NIRF 31 , PET/CT with BLI 32 or SPECT/CT with BLI & NIRF 33,34 . However, as radiation from both CT based anatomical imaging and radioisotopes can influence organ and cell biology leading to biased experimental data 7 , we developed a non radiation-based imaging platform.…”