OBJECTIVE: Regional lymph node (LN) volume decreases after neoadjuvant therapy, requiring a tracer for more accurate detection. Nano-carbon tracer is a third-generation tracer with several advantages, but its use for LN detection after neoadjuvant chemoradiotherapy for middle and low rectal cancer remains unclear. Therefore, this study investigated the effects and safety of anoscope-guided subrectal injections of nano-carbon suspension in this patient population.
METHODS: This study retrospectively reviewed the medical records of 45 patients with middle and low rectal cancer admitted to our institution from March 2019 to March 2022. All patients received preoperative neoadjuvant chemotherapy and radiotherapy and were divided into nano-carbon injection (n = 23; anoscope-guided injections of nano-carbon suspension in the rectal submucosa 2 cm above the dentate line 24 h preoperatively) and control (n = 22; directly underwent surgery) groups. The LN detection and complication rates were compared between the groups.
RESULTS: The total and mean numbers of LNs and small LNs and the number of patients with > 12 LNs were significantly higher in the nano-carbon injection group than in the control group. The total number of positive LNs and LN metastasis did not differ between the groups, nor did the anastomotic leakage, bleeding, stenosis, and abscess occurrence rates.
CONCLUSIONS: Anoscope-guided nano-carbon lymphatic tracing increased the LN detection rate, caused less trauma, and resulted in fewer postoperative complications than the direct surgical procedure. Thus, it is an effective, safe, and practical method that may improve dissections and the postoperative pathological staging accuracy.

Nitric oxide (NO) plays a pivotal role as a biological signaling molecule, presenting challenges in its specific detection and differentiation from other reactive nitrogen and oxygen species within living organisms. Herein, a 18F-labeled (fluorine-18, t1/2 = 109.7 min) small-molecule tracer dimethyl 4-(4-(4-[18F]fluorobutoxy)benzyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate ([18F]BDHP) is developed based on the dihydropyridine scaffold for positron emission tomography (PET) imaging of NO in vivo. [18F]BDHP exhibits a highly sensitive and efficient C-C cleavage reaction specifically triggered by NO under physiological conditions, leading to the production of a 18F-labeled radical that is readily retained within the cells. High uptakes of [18F]BDHP are found within and around NO-generating cells, such as macrophages treated with lipopolysaccharide or benzo(a)pyrene. MicroPET/CT imaging of arthritic animal model mice reveals distinct tracer accumulation in the arthritic legs, showcasing a higher distribution of NO compared with the control legs. In summary, a specific radical-generating dihydropyridine tracer with a unique radical retention strategy has been established for the marking of NO in real-time in vivo.

Compounds 8a-j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for high-affinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [18F]FTT, [18F]8a, [18F]8d, and [18F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [18F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [18F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [18F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [18F]BIBD-300 was greater than that of [18F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [18F]FTT, which mainly relies on hepatobiliary clearance, [18F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [18F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [18F]FTT, [18F]BIBD-300, and [18F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [18F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [18F]FTT and [18F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [18F]FTT and [18F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [18F]BIBD-300 is a new option for an excellent PARP-1 tracer.

By modifying the structures of targeted A2AR antagonists and tracers, novel compounds 3, 7a, 9, 12c, and BIBD-399 were designed and synthesized. In vitro inhibition experiments demonstrated that 3, 12c, and BIBD-399 have high affinity for A2AR. [18F]3 and [18F]BIBD-399 were successfully synthesized. In terms of biological distribution, the brain uptake of [18F]MNI-444 exhibits greater than that of [18F]3 and [18F]BIBD-399. PET imaging shows that [18F]3 is off-target in the brain, while [18F]BIBD-399 and [18F]MNI-444 can be specifically imaged in regions with high A2AR expression. Differently, [18F]BIBD-399 could quickly reach equilibrium in the targeted region within 10 min after administration, while [18F]MNI-444 shows a slowly increasing trend within 2 h of administration. [18F]BIBD-399 is mainly metabolized by the liver and kidney, and there is no obvious defluorination in vivo. Additional in vitro autoradiography showed that the striatal signals of [18F]BIBD-399 and [18F]MNI-444 were inhibited by the A2AR antagonist SCH442416 but not by the A1R antagonist DPCPX, demonstrating the high A2AR binding specificity of [18F]BIBD-399. Molecular docking further confirms the high affinity of MNI-444 and BIBD-399 for A2AR. Further tMCAo imaging showed that [18F]BIBD-399 can sensitively distinguish between infarcted and noninfarcted sides, a capability not observed with [18F]MNI-444. Given its pharmacokinetic properties and the ability to identify lesion regions, [18F]BIBD-399 has potential advantages in monitoring A2AR changes, meriting further clinical investigation.

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts in more than 90% of epithelial tumors. Several radiotracers targeting FAPs have been used in clinical settings in recent years. However, the number of 18F-labeled FAP tracers is still limited. Herein, we aimed to develop 18F-labeled FAP tracers with optimized pharmacokinetics. Labeling precursors (NOTA-DD-FAPI and NOTA-PD-FAPI) were synthesized and labeled with fluorine-18. The precursors NOTA-DD-FAPI (IC50 = 0.21 ± 0.06 nM) and NOTA -PD-FAPI (IC50 = 0.13 ± 0.07 nM) showed a higher affinity for FAP compared to NOTA-FAPI-42 (IC50 = 0.66 ± 0.19 nM). Novel 18F-labeled FAP tracers showed a specific uptake, high internalized fraction, and low cellular efflux in vitro. Compared to the clinically used tracer [18F]AlF-FAPI-42, both the novel 18F-labeled FAP tracers, and especially the [18F]AlF-PD-FAPI tracer with a higher tumor-to-background ratio demonstrated rapid renal excretion and higher tumor uptake during preclinical evaluation, resulting in images with higher contrast. Thus, [18F]AlF-PD-FAPI shows promise for use as a FAP-targeting tracer for clinical translation.

Tracing water sources of streamflow in a mixed land-use catchment is critical for predicting pollutant emissions from various human activities to streams but remains a major challenge. A rain event based field monitoring study was conducted in the Jieliu catchment located in the hilly area of central Sichuan Province, southwest China. The ratio of the maximum fluorescence intensities (Fmax) of the two humic-like dissolved organic matter (DOM) components at excitation/emission wavelengths of 255 (315)/415 nm (component 1; C1) and 260 (375)/480 nm (component 2; C2) was proposed as a tracer for quantifying streamflow water sources. Satisfactory performance of using the Fmax(C1)/Fmax(C2) ratio in hydrograph separation of streamflow at the outlet of a forest sub-catchment was verified by through comparison with the hydrograph separation results based on δ18O data. The Fmax(C1)/Fmax(C2) ratio was then applied to estimate the contributions of rainwater and pre-event water sources under different land use types to the streamflow in an agro-forest sub-catchment and the entire catchment. The hydrograph separation results using the Fmax(C1)/Fmax(C2) ratio can be used to support the optimization of water resource management and the quantification of pollutant loadings from major water sources to streams at the catchment scale.

Purpose: To explore the clinical application value of indocyanine green (ICG)-rituximab in sentinel lymph node biopsy. Methods: This study included 156 patients with primary breast cancer: 50 patients were enrolled in dose-climbing test, and 106 patients were enrolled in verification test. This was to compare the consistency of ICG-rituximab and combined method in the detected lymph nodes. Results: According to the verification test, the imaging rate of ICG-rituximab was 97.3%. Compared with the combined method, the concordance rate of fluorescence method was 0.991 (28 + 78/107; p < 0.001). Conclusion: For ICG-rituximab as a fluorescent targeting tracer, the optimal imaging dose of ICG 93.75 μg/rituximab 375 μg can significantly reduce the imaging of secondary lymph nodes. Compared with the combined method, it has a higher concordance rate.

Glutamine metabolism-related tracers have the potential to visualize numerous tumors because glutamine is the second largest source of energy for tumors. (2S,4S)-4-[18F]FEBGln was designed by introducing [18F]fluoroethoxy benzyl on carbon-4 of glutamine. The aim of this study was to investigate the pharmacokinetic properties and tumor positron emission tomography (PET) imaging characteristics of (2S,4S)-4-[18F]FEBGln in detail. The biodistribution results of nude mice bearing MCF-7 tumor showed that (2S,4S)-4-[18F]FEBGln had high initial tumor uptake, and a fast clearance rate, resulting in a high tumor-to-muscle ratio at 30 min postinjection. There was no obvious defluorination in vivo. The micro-PET-CT imaging results of (2S,4S)-4-[18F]FEBGln orthotopic MCF-7 tumor-bearing nude mice were consistent with the biological distribution results. Compared with (2S,4R)-4-[18F]FGln, (2S,4S)-4-[18F]FEBGln showed poor tumor retention, but its clearance in normal tissues was also fast, so it had better PET image contrast than the former. Unlike poor retention in MCF-7-bearing nude mice, (2S,4S)-4-[18F]FEBGln has good retention in NCI-h1975 and 22Rv1 tumor models. Since (2S,4S)-4-[18F]FEBGln has low uptake in normal lungs and high uptake in the bladder, it is expected to be used in the accurate diagnosis of lung cancer but cannot accurately determine prostate cancer. Consistent with the advantages of radiolabeled amino acids in the application of brain tumors, (2S,4S)-4-[18F]FEBGln accurately diagnoses U87MG glioma with higher contrast than [18F]FET and [18F]FDG, and there is a correlation between (2S,4S)-4-[18F]FEBGln uptake and tumor growth cycle. Further kinetic model analysis showed that (2S,4S)-4-[18F]FEBGln was similar to (2S,4R)-4-[18F]FGln, conforming to the one-compartment model and the Logan graphical model, and was expected to assess the size of the glutamine pool of the tumor. Therefore, (2S,4S)-4-[18F]FEBGln is expected to provide a strong imaging basis for the diagnosis, formulation of personalized plans, and efficacy evaluation of glioma, lung cancer, and breast cancer.

UNASSIGNED: Many breast cancer patients have avoided axillary lymph node dissection after sentinel lymph node biopsy (SLNB). During the SLNB operation, the color of lymphatic vessels is sometimes poor and so finding them is difficult. This study observed the tracing effects of three tracer combinations and also reported our experience in simplifying the SLNB program.
UNASSIGNED: In total, 123 breast cancer patients whose TNM stage was cT1-2N0M0 were retrospectively studied. According to the tracer used, the patients were divided into the carbon nanoparticle (CNP) group (38 cases), CNP combined with methylene blue (CNP + MB) group (41 cases), and indocyanine green combined with MB (ICG + MB) group (44 cases). All 123 breast cancer cases were also classified into the non-tracking group (53 cases) and tracking group (70 cases) according to the SLNB operation process. The non-tracking group looked for the stained sentinel lymph nodes directly, while the tracking group looked for the stained lymph nodes along the lymphatic vessels.
UNASSIGNED: The SLN identification rates in the CNP, CNP + MB, and ICG + MB groups were 97.4%, 97.6%, and 95.5% respectively (P > 0.05). The average number of SLNs detected was 4.92 ± 2.06, 5.12 ± 2.18, and 4.57 ± 1.90, respectively (P > 0.05). The ideal display rates of lymphatic vessels in the three groups were 86.8%, 87.8%, and 93.2%, respectively (P > 0.05). The SLN identification rates in the non-tracking and tracking groups were 96.2% and 97.1%, respectively (P > 0.05). The average number of SLNs detected were 5.73 ± 1.76 and 5.70 ± 1.93, respectively (P > 0.05), and the average operation time was 16.47 ± 5.78 and 27.53 ± 7.75 min, respectively (P < 0.05).
UNASSIGNED: This is the first study to observe the application effect of CNP combined with MB and ICG combined with MB tracers in SLNB of breast cancer patients. No significant difference was observed among the patients in SLN identification and lymphatic vessel display. Omitting the step of searching for lymphatic vessels in SLNB surgery does not reduce the surgical effect, but the reduced operating steps can reduce the surgical time and theoretically reduce postoperative complications.

UNASSIGNED: Exploratory study of the effect and clinical value of carbon nanoparticle suspension injection (CNSI) as a tracer for inguinal sentinel lymph nodes in penile cancer.
UNASSIGNED: We selected 29 patients with penile cancer in our department from January 2019 to October 2022. According to whether the CNSI tracer was injected during the pathological biopsy of the inguinal lymph nodes, the enrolled patients were assigned to the control group, the group in which CNSI was injected 12 h before the surgery (12HBS group) and the group in which CNSI was injected 0.5 h before the surgery (0.5HBS group). Evaluating the effectiveness of CNSI as a lymphatic tracer involves analyzing the following: its safety, the statistical analysis of the detection rate (DR) of different groups, the number of lymph nodes sent for each case (NOLNSFEC), the difference of positive rate of lymphatic metastasis (PROLM), and operation time (OT).
UNASSIGNED: The lymph nodes in the 12HBS group and 0.5HBS group had an obvious black staining appearance, and no adverse reactions or surgical complications were found. Most of the black-stained areas caused by CNSI injection were removed with penile excision, which did not affect the postoperative appearance. This did not affect the pathological analysis. The DR of lymph nodes in the 12HBS group was higher (p < 0.05) than that in the control group. More lymph nodes were removed for examination (p < 0.05), which improved the efficiency of surgery. Compared with the 12HBS group, the number of lymph nodes removed in the 0.5HBS group decreased (p < 0.05). The OT was shortened (p < 0.05), but there was no significant difference in the DR and PROLM.
UNASSIGNED: CNSI was applied to the naked-eye tracing of inguinal sentinel lymph nodes in penile cancer, which is safe and efficient. Injection of CNSI 0.5 h before surgery can help identify the \"foremost position\" of sentinel lymph nodes and reduce surgical trauma.