DNA tetrahedron nanostructure (DTNs) has the merits of simple synthesis, high yield, structural stability, and mechanical rigidity, and its three-dimensional structure provides a satisfactory biosensing interface to the improvement of the binding efficiency of antigenic proteins and antibodies. Electrochemiluminescence (ECL) reagent, tris-(4,4′-dicarboxylicacid-2,2′-bipyridyl)ruthenium(II) dichloride (Ru(dcbpy) 3 Cl 2 ), was modified on the electrode through the formation of classical sandwich complex of antibody− antigen−antibody. ECL response of the system increased with the increment of the target (golgi protein 73 (GP73) in this study) with high selectivity. Besides, the composed double-stranded DNA (dsDNA) in each side of DTNs could act as an excellent carrier of methylene blue (MB), thus producing a stable electrochemical internal reference signal on the electrode surface to correct the potential interferences. Therefore, a highly selective and reproductive ratiometric immunosensor was developed on the basis of the ratio of ECL of Ru(dcbpy) 3 Cl 2 and electrochemistry of MB. The ratio value of the ECL/ electrochemistry had a linear relationship with GP73 concentration in the range of 15 pg/mL−0.7 ng/mL, and the limit of detection was 15 pg/mL. The proposed ratiometric ECL immunoassay has been applied to detect GP73 in real serum samples with satisfactory results.

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A label-free aptamer-based electrochemical impedance biosensor was developed for convenient and rapid detection of serum tumor biomarker CD44.

Background: The choice of 68Ga-DOTA-1-Nal3-octreotide (68Ga-DOTA-NOC) injected dose and Position emission tomography/computer tomography (PET/CT) acquisition time is still a challenge for obtaining consistently high-quality PET image. Objective: To determine the optimal acquisition protocols based on patient body mass index (BMI) and the injected dose per kilogram for 68Ga-DOTA-NOC PET/CT imaging. Patients and Methods: This was a retrospective analysis of 51 patients (21 males and 30 females) who underwent clinical 68Ga-DOTANOC PET/CT imaging from November 2016 to March 2018 in Nanjing first hospital, the average BMI of these patients was 23.18 ± 3.45 kg/m2 with injected dose of 39.55–110.11 MBq. The study population was classified into groups based on Chinese standard BMI and injected dose. PET image quality and acquisition time were evaluated by coefficient of variance (CV) in the liver slice. Results: (1) The CV significantly increased with increasing weight and BMI (r = 0.647, 0.483, all P < 0.01), and significantly decreased with increasing injected dose per kilogram (r = 0 695, P < 0.01). (2) The CV differed significantly among 4 BMI-based groups, except for normal-weight group versus overweight group and overweight group versus obese group (P < 0.01), and the ratio of overweight group and obese group to normal weight group was approximately 1.1 and 1.2, respectively. Meanwhile, the CV had a significant statistical difference among 3 injected dose per kilogram groups (P < 0.01), and the ratio of that for low dose group and high dose group to moderate dose group was approximately 1.2 and 0.8. Conclusion: The findings showed a feasibility of obtaining consistently high-quality PET image at low injected dose and shorter acquisition time. Estimation of optimal acquisition time and injected dose using CV is valid in improving PET image quality, which can provide reference for the establishment and promotion of 68Ga-DOTA-NOC imaging protocols in China.

Overexpression of fibroblast activation protein (FAP) in cancer-associated fibroblasts in a wide variety of tumors enables a highly selective targeting strategy using FAP inhibitors (FAPIs). Quinoline-based FAPIs labeled with radionuclides have been widely developed for tumor-targeted nuclear medicine imaging. However, the short retention time of FAPIs at the tumor site limits their application in radionuclide therapy. In this study, a novel FAPI-04 dimer was synthesized and labeled with radionuclides to prolong the retention time in tumors for imaging and therapy. To prepare the FAPI-04 dimer complex, DOTA-Suc-Lys-(FAPI-04) 2 , we used Fmoc-Lys(Boc)−OH as the linker to conjugate two FAPI-04 structures by an amide reaction. The resulting product was further modified by DOTA groups to allow for conjugation with radioactive metals. Both [ 68 Ga]Ga-(FAPI-04) 2 and [ 177 Lu]Lu-(FAPI-04) 2 showed a radiochemical purity of >99% and remained stable in vitro. In vivo, micro-PET images of SKOV3, A431, and H1299 xenografts revealed that the tumor uptake of [ 68 Ga]Ga-(FAPI-04) 2 was about twice that of [ 68 Ga]Ga-FAPI-04 and that the accumulation of [ 68 Ga]Ga-(FAPI-04) 2 at the tumor site did not significantly decrease even 3h after injection. The tumor−abdomen ratio of [ 68 Ga]Ga-(FAPI-04) 2 images was significantly higher than that of [ 18 F]F-FDG images. For radionuclide therapy, [ 177 Lu]Lu-(FAPI-04) 2 effectively retarded tumor growth and displayed good tolerance. In conclusion, the DOTA-Suc-Lys-(FAPI-04) 2 design enhanced its uptake in FAP-expressing tumors, improved its retention time at the tumor site, and produced high-contrast imaging in xenografts after radionuclide labeling. Furthermore, it showed a noticeable antitumor effect. DOTA-Suc-Lys-(FAPI-04) 2 provides a new approach for applying FAPI derivatives in tumor theranostics.

Herein, an amphiphilic block copolymer CD44-targeting peptide-conjugated polyethylene glycol-block-hydroxyethyl starch-block-poly (L-lactic acid) (CD44p-conjugated PEG-b-HES-b-PLA) are synthesized, which could self-assemble into the pH-responsive and CD44-targeting polymer micelles against breast cancer cells MDA-MB-231. Emodin (Emo) is a natural anthraquino with pharmacological activities in anti-tumor effects. However, Emo suffers from poor water solubility, low biocompatibility, rapid systemic elimination, and off-target side effects, resulting in unsatisfactory treatment outcomes. Nanotechnology-based drug delivery systems have proven great potential for cancer chemotherapy. The constructed polymeric micelles Emo@CD44p-PM have exhibited an average size of 154.5 ± 0.9 nm characterized by DLS and TEM. Further, the Emo@CD44p-PM have effective Emo-loading capacity, good thermal stability, and pH responsiveness. Intracellular uptake study shows the enhanced cellular internalization of Emo@CD44p-PM due to the increased exposure of CD44p enhances the cellular internalization of Emo@CD44p-PM effectively. Furthermore, the in vitro results showed Emo@CD44p-PM has been observed good biocompatibility and anti-tumor effects. Therefore, the polymeric micelles Emo@CD44p-PM provide a promising delivery strategy of targeted therapy for breast cancer.

Background To investigate the influence of small voxel Bayesian penalized likelihood (SVB) reconstruction on small lesion detection compared to ordered subset expectation maximization (OSEM) reconstruction using a clinical trials network (CTN) chest phantom and the patients with 18F-FDG-avid small lung tumors, and determine the optimal penalty factor for the lesion depiction and quantification. Methods The CTN phantom was filled with 18F solution with a sphere-to-background ratio of 3.81:1. Twenty-four patients with 18F-FDG-avid lung lesions (diameter < 2 cm) were enrolled. Six groups of PET images were reconstructed: routine voxel OSEM (RVOSEM), small voxel OSEM (SVOSEM), and SVB reconstructions with four penalty factors: 0.6, 0.8, 0.9, and 1.0 (SVB0.6, SVB0.8, SVB0.9, and SVB1.0). The routine and small voxel sizes are 4 × 4 × 4 and 2 × 2 × 2 mm3. The recovery coefficient (RC) was calculated by dividing the measured activity by the injected activity of the hot spheres in the phantom study. The SUVmax, target-to-liver ratio (TLR), contrast-to-noise ratio (CNR), the volume of the lesions, and the image noise of the liver were measured and calculated in the patient study. Visual image quality of the patient image was scored by two radiologists using a 5-point scale. Results In the phantom study, SVB0.6, SVB0.8, and SVB0.9 achieved higher RCs than SVOSEM. The RC was higher in SVOSEM than RVOSEM and SVB1.0. In the patient study, the SUVmax, TLR, and visual image quality scores of SVB0.6 to SVB0.9 were higher than those of RVOSEM, while the image noise of SVB0.8 to SVB1.0 was equivalent to or lower than that of RVOSEM. All SVB groups had higher CNRs than RVOSEM, but there was no difference between RVOSEM and SVOSEM. The lesion volumes derived from SVB0.6 to SVB0.9 were accurate, but over-estimated by RVOSEM, SVOSEM, and SVB1.0, using the CT measurement as the standard reference. Conclusions The SVB reconstruction improved lesion contrast, TLR, CNR, and volumetric quantification accuracy for small lesions compared to RVOSEM reconstruction without image noise degradation or the need of longer emission time. A penalty factor of 0.8–0.9 was optimal for SVB reconstruction for the small tumor detection with 18F-FDG PET/CT.

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