In vivo quantifying molecular specificity of Cy55-labeled cyclic 9-mer peptide probe with dynamic fluorescence imaging

Abstract

We quantified molecular specificity of Cy5.5-GX1 in vivo with dynamic fluorescence imaging to better understand its kinetic properties. According to whether or not free GX1 was injected and when it was injected, twelve of BGC-823 xenografted mice were randomly divided into three groups and underwent a 60 minute dynamic fluorescence scanning. Combined with a principal-component analysis, the binding potential (Bp) of the probe was determined by both Logan graphical analysis with reference tissue model (GARTM) and Lammertsma simplified reference tissue model (SRTM). The sum of the pharmacokinetic rate constants (SKRC) was quantified by the Gurfinkel exponential model (GEXPM). Cy5.5-GX1 specifically targeted tumor both in vitro and in vivo. We obtained similar quantification results of Bp (GARTM Bp = 0.582 ± 0.2655, SRTM Bp = 0.618 ± 0.2923), and obtained a good linear relation between the Bp value and the SKRC value. Our results indicate that the SKRC value is more suitable for an early-stage kinetic data analysis, and the Bp value depicts kinetic characteristics under the equilibrium state. Dynamic fluorescence imaging in conjunction with various kinetic models are optimal tools to quantify molecular specificity of the Cy5.5-GX1 probe in vivo.

Investigation of the influence of sampling schemes on quantitative dynamic fluorescence imaging

“…Cy5.5-GX1 synthesized by FanBo Co. Ltd. (Beijing, China) and its characterization had been done in our previous work [13].…”

“…Detailed description of kinetic models and related parameters can be found in [13]. Here, the GARTM model was applied to calculate the BP values, which can be expressed as Eq.…”

“…If we can get relatively robust dynamic parameters in case of missing some time points immediately after the injection of the probe, the experimental operations can be much simpler. In current dynamic FI, the sampling sparsity and sampling uniformity were usually empirically determined [8][9][10][11][12][13]. Too small a sampling interval results in heavier camera burden and data processing burden, but too large a sampling interval results in an unsatisfactory recovery of the time activity curve (TAC), which may affect the accuracy of the determination of kinetic parameters.…”

Novel vinyl-modified RGD conjugated silica nanoparticles based on photo click chemistry for in vivo prostate cancer targeted fluorescence imaging

“…Amongst these approaches, uorescence imaging is considered to be one of the most promising methods for early tumor diagnosis and treatment, because it is cost effective, highly sensitive, radiation free, enables rapid imaging and is easy to quantify. [3][4][5][6] This approach requires the availability of high-quality molecular probes for the selective visualization and early diagnosis of tumors in vivo. Selective tumor targeting has oen been achieved through conjugation of a molecular imaging nanoprobe to tumor directing antibodies or polypeptides.…”

Investigation of injection dose and camera integration time on quantifying pharmacokinetics of a Cy5.5-GX1 probe with dynamic fluorescence imagingin vivo

“…10 Unfortunately, the in vivo pharmacokinetic properties of GX1 have not been fully studied yet. 11 The injection dose (ID) of the GX1-based probe used in current studies is often determined according to experience, and the optimal dose is also unexplored. Appropriate ID of targeted probes not only avoids receptor oversaturation and wasting of probes but also can avoid the phenomenon of image overexposure caused by excessive probe injections.…”