Extracellular matrix (ECM) accumulation in liver fibrosis is caused by the activation of hepatic stellate cells (HSCs). The goal of this study was to develop a 99mTc-labeled N-acetylglucosamine (GlcNAc) that specifically interacts with desmin and vimentin expressed on activated HSCs to monitor the progression and prognosis of liver fibrosis using single-photon emission computed tomography (SPECT) imaging.Methods: GlcNAc-conjugated polyethylenimine (PEI) was first prepared and radiolabeled with 99mTc. Noninvasive SPECT imaging with 99mTc-GlcNAc-PEI was used to assess liver fibrosis in a carbon tetrachloride (CCl4) mouse model. The liver uptake value (LUV) of 99mTc-GlcNAc-PEI was measured by drawing the region of interest (ROI) of the whole liver as previously suggested. The LUV of the CCl4 groups was compared with that of the olive oil group. Next, we estimated the correlation between the results of SPECT imaging and physiological indexes. After treatment with clodronate liposome, the LUV of 99mTc-GlcNAc-PEI in fibrotic mice was compared with that in control mice.Results: 99mTc-GlcNAc-PEI is a hydrophilic compound with high radiochemical purity (>98%) and good stability. It could specifically target desmin and vimentin on the surface of activated HSCs with high affinity (the Kd values were 53.75 ± 9.50 nM and 20.98 ± 3.56 nM, respectively). The LUV of 99mTc-GlcNAc-PEI was significantly different between the CCl4 and control groups as early as 4 weeks of CCl4 administration (3.30 ± 0.160 vs 2.34 ± 0.114%/cc; P ˂ 0.05). There was a strong correlation between the LUV and Sirius Red quantification (R = 0.92, P ˂ 0.001). Compared with control, clodronate liposome treatment reduced the LUV of 99mTc-GlcNAc-PEI (4.62 ± 0.352 vs 2.133 ± 0.414%/cc; P ˂ 0.05).Conclusion: 99mTc-GlcNAc-PEI SPECT/CT was useful in assessing liver fibrosis and monitoring the treatment response.

Assessment of myocardial viability is deemed necessary to aid in clinical decision making whether to recommend revascularization therapy for patients with myocardial infarction (MI). Dianthraquinones such as hypericin (Hyp) selectively accumulate in necrotic myocardium, but were unsuitable for early imaging after administration to assess myocardial viability. Since dianthraquinones can be composed by coupling two molecules of monomeric anthraquinone and the active center can be found by splitting chemical structure, we propose that monomeric anthraquinones may be effective functional groups for necrosis targetability. In this study, eight radioiodinated monomeric anthraquinones were evaluated as novel necrosis avid agents (NAAs) for imaging of necrotic myocardium. All 131I-anthraquinones showed high affinity to necrotic tissues and 131I-rhein emerged as the most promising compound. Infarcts were visualized on SPECT/CT images at 6 h after injection of 131I-rhein, which was earlier than that with 131I-Hyp. Moreover, 131I-rhein showed satisfactory heart-to-blood, heart-to-liver and heart-to-lung ratios for obtaining images of good diagnostic quality. 131I-rhein was a more promising “hot spot imaging” tracer for earlier visualization of necrotic myocardium than 131I-Hyp, which supported further development of radiopharmaceuticals based on rhein for SPECT/CT (123I and 99mTc) or PET/CT imaging (18F and 124I) of myocardial necrosis.

Currently, only a few 18 F-radiolabeling methods were conducted in aqueous media, with non-macroelement fluoride acceptors and stringent conditions required. Herein, we describe a one-step non-solvent-biased, room-temperature-driven 18 F-radiolabeling methodology based on organophosphine fluoride acceptors. The high water tolerance for this isotope-exchange-based 18 F-labeling method is attributed to the kinetic and thermodynamic preference of F/F over the OH/F substitution based on computational calculations and experimental validation. Compact [ 18/19 F]di- tert -butyl-organofluorophosphine and its derivatives used as 18 F-labeling synthons exhibit excellent stability in vivo. The synthons are further conjugated to several biomolecular ligands such as c(RGDyk) and human serum albumin. The one-step labeled biomolecular tracers demonstrate intrinsic target imaging ability and negligible defluorination in vivo. The current method thus offers a facile and efficient 18 F-radiolabeling pathway, enabling further widespread application of 18 F.

With further research into the molecular mechanisms and roles linking immune suppression and restraint of (pre)malignancies, immunotherapies have revolutionized clinical strategies in the treatment of cancer. However, nearly 70% of patients who received immune checkpoint therapeutics showed no response. Complementary and/or synergistic effects may occur when extracellular checkpoint antibody blockades combine with small molecules targeting intracellular signal pathways up/downstream of immune checkpoints or regulating the innate and adaptive immune response. After radiolabeling with radionuclides, small molecules can also be used for estimating treatment efficacy of immune checkpoint blockades. This review not only highlights some significant intracellular pathways and immune-related targets such as the kynurenine pathway, purinergic signaling, the kinase signaling axis, chemokines, etc., but also summarizes some attractive and potentially immunosuppression-related small molecule agents, which may be synergistic with extracellular immune checkpoint blockade. In addition, opportunities for small molecule-based theranostics in cancer immunology will be discussed.

ABSTRACT:Myocardial infarction (MI) leads to substantial morbidity and mortality around the world.Accurate assessment of myocardial viability is essential to assist therapies and improve patient outcomes. 131 I-hypericin dicarboxylic acid ( 131 I-HDA) was synthesized and evaluated as a potential diagnostic agent for earlier assessment of myocardium viability compared to its preceding counterpart 131 I-hypericin ( 131 I-Hyp) with strong hydrophobic property, long plasma half-life and high uptake in mononuclear phagocyte system (MPS). Herein, HDA was synthesized and characterized, and self-aggregation constant K α was analyzed by spectrophotometry. Plasma half-life was determined in healthy rats by γ-counting. 131 I-HDA and 131 I-Hyp were prepared with iodogen as oxidant. In vitro necrosis avidity of 131 I-HDA and 131 I-Hyp was evaluated in necrotic cells induced by hyperthermia. Biodistribution was determined in rat models of induced necrosis using γ-counting, autoradiography, and histopathology. Earlier imaging of necrotic myocardium to assess myocardial viability was performed in rat models of reperfused myocardium infarction using single photon emission computed tomography/computed tomography (SPECT/CT). As a result, the self-aggregation

In this study, radioiodinated 4-(p-iodophenyl)butyric acid ([ 131 I]IBA) was synthesized and evaluated as a portable albumin-binder for potential applications in single photon emission computed tomography imaging of blood pool, tumor, and lymph node with significantly improved pharmacokinetic properties. The [ 131 I]IBA was prepared under the catalyst of Cu 2 O/1,10-phenanthroline. After that, the albuminbinding capability of [ 131 I]IBA was tested in vitro, ex vivo, and in vivo, respectively. [ 131 I]IBA was obtained with very high radiolabeling yield (>99%) and good radiochemical purity (>98%) within 10 min. It binds to albumin effectively with high affinity (IC 50 = 46.5 μM) and has good stability. The results of biodistribution indicated that the [ 131 I]IBA was mainly accumulated in blood with good retention (10.51 ± 2.58% ID/g at 30 min p.i. and 4.63 ± 0.17%ID/g at 4 h p.i.). In the SPECT imaging of mice models with [ 131 I]IBA, blood pool, lymph node, and tumors could be imaged clearly with high target-to-background ratio. Overall, the radioiodinated albumin binder of [ 131 I]IBA with long blood half-life and excellent stability could be used to decorate diversified albumin-binding radioligands and developed as a versatile theranostic agent.

Although photoacoustic imaging (PAI) in the second near-infrared (NIR-II) region (1.0–1.7 μm) is admired for deeper penetration and higher contrast, few organic NIR-II absorbers are available as exogenous contrast agents in vivo. A1094 belongs to the very few ∼1.1 μm absorbing croconaine dyes that have superior extinction coefficient and tend to form irregular aggregation. In this study, shape-controlled A1094@DSPE-PEG2000 micelles with a J-aggregate core with remarkable 1.2–1.3 μm absorption are fabricated as biocompatible organic agents. Excellent capabilities in photothermal conversion, photostability, and PAI are found in in vitro studies. In vivo PAI of inguinal lymph nodes and in situ glioma pre- and post-resection, all demonstrate high lymph/tumor-targeting efficiency. An ∼4.54 mm deep brain lesion is imaged at 1200 nm with minimized background and increased contrast compared to 970 nm. Overall, we achieved significant bathochromic shift of organic absorbers and expanded their PAI application to the long-wavelength end of the NIR-IIa region.

The purpose of this study is to develop a specific CXCR4-targeting radioiodinated agent (I- or I-pentixather) for single-photon-emission-computed-tomography (SPECT) imaging of CXCR4 expression in myocardial-infarction-reperfusion (MI/R) rat models. After SPECT-CT imaging withI-pentixather at 4, 12, and 36 h and 3 and 7 days after MI/R, the models were validated by ex vivo autoradiography, TTC staining, and immunohistochemistry and in vivo echocardiography and classical Tc-MIBI perfusion imaging. The SPECT-CT images showed that the infarcted myocardium (IM) could be visualized with high quality as early as 4 h and reached the maximum at 3 days after MI/R and that CXCR4 upregulation was still visible at 7 days after MI/R. In the biodistribution study, high uptakes in the IM (0.99 ± 0.13, 1.52 ± 0.29, 1.75 ± 0.22, 1.94 ± 0.27, and 0.61 ± 0.14% ID/g at 4, 12, and 36 h and 3 and 7 days after MI/R, respectively) were observed that were much higher than that of normal myocardium. The highest uptake was reached at 3 days after MI/R, which agreed well with the SPECT results. In addition, the radioactivity uptakes of the IM in both the biodistribution and SPECT imaging could be blocked effectively by excess amounts of AMD3465, indicating the high specificity of radioiodinated pentixather to CXCR4. On the basis of its promising properties,I-pentixather may serve as a powerful CXCR4-expression diagnostic probe for evaluating lesions and monitoring therapy responses in patients with cardiovascular diseases.