Biodistribution Study of Niosomes in Tumor-Implanted BALB/C Mice Using Scintigraphic Imaging

The purpose of this work was to study the biodistribution of niosomes in tumor-implanted BALB/c mice using gamma scintigraphy. Niosomes were first formulated and characterized, then radiolabeled with Technetium-99 m (99mTc). The biodistribution of 99mTc-labeled niosomes was evaluated in tumor-bearing mice through intravenous injection and imaged with gamma scintigraphy. The labeled complexes possessed high radiolabeling efficiency (98.08%) and were stable in vitro (>80% after 8 h). Scintigraphic imaging showed negligible accumulation in the stomach and thyroid, indicating minimal leaching of the radiolabel in vivo. Radioactivity was found mainly in the liver, spleen and kidneys. Tumor-to-muscle ratio indicated a higher specificity of the formulation for the tumor area. Overall, the formulated niosomes are stable both in vitro and in vivo, and show preferential tumor accumulation.

Scintigraphic Imaging of Neovascularization With 99mTc-3PRGD2 for Evaluating Early Response to Endostar Involved Therapies on Pancreatic Cancer Xenografts In Vivo

BackgroundMolecular imaging targeting angiogenesis can specifically monitor the early therapeutic effect of antiangiogenesis therapy. We explore the predictive values of an integrin αvβ3-targeted tracer, 99mTc-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2), for monitoring the efficacy of Endostar antiangiogenic therapy and chemotherapy in animal models.MethodsThe pancreatic cancer xenograft mice were randomly divided into four groups, with seven animals in each group and treated in different groups with 10 mg/kg/day of Endostar, 10 mg/kg/day of gemcitabine, 10 mg/kg/day of Endostar +10 mg/kg/day of gemcitabine at the same time, and the control group with 0.9% saline (0.1 ml/day). 99mTc-3PRGD2 scintigraphic imaging was carried out to monitor therapeutic effects. Microvessel density (MVD) was measured using immunohistochemical staining of the tumor tissues. The region of interest (ROI) of tumor (T) and contralateral corresponding site (NT) was delineated, and the ratio of radioactivity (T/NT) was calculated. Two-way repeated-measure analysis of variance (ANOVA) was used to assess differences between treatment groups.ResultsTumor growth was significantly lower in treatment groups than that in the control group (p < 0.05), and the differences were noted on day 28 posttreatment. The differences of 99mTc-3PRGD2 uptakes were observed between the control group and Endostar group (p = 0.033) and the combined treatment group (p < 0.01) on day 7 posttreatment and on day 14 posttreatment between the control group and gemcitabine group (p < 0.01). The accumulation of 99mTc-3PRGD2 was significantly correlated with MVD (r = 0.998, p = 0.002).ConclusionWith 99mTc-3PRGD2 scintigraphic imaging, the tumor response to antiangiogenic therapy, chemotherapy, and the combined treatment can be observed at an early stage of the treatments, much earlier than the tumor volume change. It provides new opportunities for developing individualized therapies and dose optimization.

Optimised method for normal range estimation of standardized uptake values (SUVmax, SUVmean) in liver SPECT/CT images with somatostatin analogue 99mTc-HYNIC-TOC (Tektrotyd).

Background99mTc-HYNIC-TOC (Tektrotyd) is a radiopharmaceutical used for the diagnosis of lesions with overexpression of somatostatin receptors. The purpose of this study was to optimise the method and estimate normal ranges for standardized uptake values of Tektrotyd in healthy livers. MethodsAn analysis of SUVs normal ranges was performed for images acquired in a selected “healthy group” of 42 patients evaluated for NET tumours. The “pathological group” comprised 20 patients with liver lesions detected by scintigraphic imaging. Normal ranges for radiopharmaceutical uptake values were estimated based on the quantitative analysis of images acquired with a GE Healthcare NM/CT 850 gamma camera.ResultsThe method for healthy liver segmentation in SPECT/CT was optimized. The normal range of SUVs for the liver was: SUVbw max [5.2-14.0] g/ml and SUVlbm max [3.5-9.5] g/ml. The relative standard error (relative SE) of activity concentration estimated in the phantom study for the largest hot spheres was: ϕ=37mm- 5.9%, ϕ=28mm- 7.1%, ϕ=22mm- 11.4%, and ϕ=17mm- 22%.Conclusions· Segmentation in the mid-coronal CT image, at one-fourth of the height of the liver measured from the top, with a medium-sized VOI outlined on a given transverse SPECT slice was regarded as the optimal method for estimating normal ranges for standardized uptake values.· It is necessary to standardise quantification methods in the SPECT/CT studies. Our work is a step forward in obtaining standardisation of SPECT/CT SUV calculation methods.· Calculations for radiopharmaceutical uptake in tumours with volumes smaller than 5 ml are biased with a significant measurement error.

Imaging-Based Characterization of a Slco2b1(-/-) Mouse Model Using [11C]Erlotinib and [99mTc]Mebrofenin as Probe Substrates

Organic anion-transporting polypeptide 2B1 (OATP2B1) is co-localized with OATP1B1 and OATP1B3 in the basolateral hepatocyte membrane, where it is thought to contribute to the hepatic uptake of drugs. We characterized a novel Slco2b1(-/-) mouse model using positron emission tomography (PET) imaging with [11C]erlotinib (a putative OATP2B1-selective substrate) and planar scintigraphic imaging with [99mTc]mebrofenin (an OATP1B1/1B3 substrate, which is not transported by OATP2B1). Dynamic 40-min scans were performed after intravenous injection of either [11C]erlotinib or [99mTc]mebrofenin in wild-type and Slco2b1(-/-) mice. A pharmacokinetic model was used to estimate the hepatic uptake clearance (CL1) and the rate constants for transfer of radioactivity from the liver to the blood (k2) and excreted bile (k3). CL1 was significantly reduced in Slco2b1(-/-) mice for both radiotracers (p < 0.05), and k2 was significantly lower (p < 0.01) in Slco2b1(-/-) mice for [11C]erlotinib, but not for [99mTc]mebrofenin. Our data support previous evidence that OATP transporters may contribute to the hepatic uptake of [11C]erlotinib. However, the decreased hepatic uptake of the OATP1B1/1B3 substrate [99mTc]mebrofenin in Slco2b1(-/-) mice questions the utility of this mouse model to assess the relative contribution of OATP2B1 to the liver uptake of drugs which are substrates of multiple OATPs.

Calibrated scintigraphic imaging procedures improve quantitative assessment of the cardiac sympathetic nerve activity

The 123I-labeled meta-iodobenzylguanidine (MIBG) is an analogue of noradrenaline that can evaluate cardiac sympathetic activity in scintigraphy. Quantitative analysis of 123I-MIBG images has been verified in patients with heart failure and neurodegenerative diseases. However, quantitative results differ due to variations in scintigraphic imaging procedures. Here, we created and assessed the clinical feasibility of a calibration method for 123I-MIBG imaging. The characteristics of scintigraphic imaging systems were determined using an acrylic calibration phantom to generate a multicenter phantom imaging database. Calibration factors corresponding to the scintigraphic imaging procedures were calculated from the database and applied to a clinical study. The results of this study showed that the calibrated analysis eliminated inter-institutional differences among normal individuals. In summary, our standardization methodology for 123I-MIBG scintigraphy could provide the basis for improved diagnostic precision and better outcomes for patients.