In oncologic PET, the SUV and standardized uptake ratio (SUR) of a viable tumor generally increase during the postinjection period. In contrast, the net influx rate (Ki ), which is derived from dynamic PET data, should remain relatively constant. Uptake-time-corrected SUV (cSUV) and SUR (cSUR) have been proposed as uptake-time-independent, static alternatives to Ki Our primary aim was to quantify the intrascan repeatability of Ki , SUV, cSUV, SUR, and cSUR among malignant lesions on PET/CT. An exploratory aim was to assess the ability of cSUR to estimate Ki Methods: This prospective, single-center study enrolled adults undergoing standard-of-care oncologic PET/CT. SUV and Ki images were reconstructed from dynamic PET data obtained before (∼35-50 min after injection) and after (∼75-90 min after injection) standard-of-care imaging. Tumors were manually segmented. Quantitative metrics were extracted. cSUVs and cSURs were calculated for a 60-min postinjection reference uptake time. The magnitude of the intrascan test-retest percent change (test-retest |%Δ|) was calculated. Coefficients of determination (R 2) and intraclass correlation coefficients (ICC) were also computed. Differences between metrics were assessed via the Wilcoxon signed-rank test (α, 0.05). Results: This study enrolled 78 subjects; 41 subjects (mean age, 63.8 y; 24 men) with 116 lesions were analyzed. For both tracers, SUVmax and maximum SUR (SURmax) had large early-to-late increases (i.e., poor intrascan repeatability). Among [18F]FDG-avid lesions (n = 93), there were no differences in intrascan repeatability (median test-retest |%Δ|; ICC) between the maximum Ki (Ki ,max) (13%; 0.97) and either the maximum cSUV (cSUVmax) (12%, P = 0.90; 0.96) or the maximum cSUR (cSURmax) (13%, P = 0.67; 0.94). For DOTATATE-avid lesions (n = 23), there were no differences in intrascan repeatability between the Ki ,max (11%; 0.98) and either the cSUVmax (13%, P = 0.41; 0.98) or the cSURmax (11%, P = 0.08; 0.94). The SUVmax, cSUVmax, SURmax, and cSURmax were all strongly correlated with the Ki ,max for both [18F]FDG (R 2, 0.81-0.92) and DOTATATE (R 2, 0.88-0.96), but the cSURmax provided the best agreement with the Ki ,max across early-to-late time points for [18F]FDG (ICC, 0.69-0.75) and DOTATATE (ICC, 0.90-0.91). Conclusion: Ki ,max, cSUVmax, and cSURmax had low uptake time dependence compared with SUVmax and SURmax The Ki ,max can be predicted from cSURmax.

Liver cancer is a leading cause of cancer deaths worldwide. Surgical resection of superficial hepatic lesions is increasingly guided by the disrupted bile excretion of the fluorescent dye indocyanine green (ICG). To extend this approach to deeper lesions, a dedicated bimodal tracer that facilitates both fluorescence guidance and radioguidance was developed. Methods: A tracer comprising a methylated cyanine-5 (Cy5) fluorescent dye and a mercaptoacetyltriserine chelate (hHEPATO-Cy5) was synthesized and characterized. Cellular uptake and excretion were evaluated in hepatocyte cultures (2-dimensional culture and in vitro lesion model), using a fluorescent bile salt, MitoTracker dye, and methylated Cy5 as a control. After radiolabeling, the pharmacokinetics of 99mTc-hHEPATO-Cy5 were assessed in mice over 24 h (percentage injected dose and percentage injected dose per gram of tissue, SPECT/CT imaging and fluorescence imaging). The ability to provide real-time fluorescence guidance during robot-assisted hepatobiliary surgery was evaluated in a porcine model using ICG as a reference. Results: The unique molecular signature of hHEPATO-Cy5 promotes hepatobiliary excretion. In vitro studies on hepatocytes showed that where methylated Cy5 remained internalized, hHEPATO-Cy5 showed fast clearance (10 min) similar to that of fluorescent bile salt. In vivo use of 99mTc-hHEPATO-Cy5 in mice revealed liver accumulation and rapid biliary clearance. The effectiveness of bile clearance was best exemplified by the 2-orders-of-magnitude reduction in count rate for the gallbladder (P = 0.008) over time. During hepatobiliary surgery in a porcine model, hHEPATO-Cy5 enabled fluorescence-based lesion identification comparable to that of ICG. Conclusion: The bimodal 99mTc-hHEPATO-Cy5 provides an effective means to identify liver lesions. Uniquely, it helps overcome the shortcomings of fluorescence-only approaches by allowing for an extension to in-depth radioguidance.

The demand for PET tracers that target prostate-specific membrane antigen (PSMA) continues to increase. Meeting this demand with approved 68Ga- and 18F-labeled PSMA tracers is challenging outside of major urban centers. This is because the short physical half-life of these radionuclides makes it necessary to produce them near their sites of usage. To overcome this challenge, we propose cyclotron-produced 61Cu for labeling PSMA PET tracers. 61Cu can be produced on a large scale, and its 3.33-h half-life allows shipping over considerably longer distances than possible for 68Ga and 18F. Production of true theranostic twins using 61Cu and the β--emitter 67Cu is also feasible. Methods: PSMA-I&T (DOTAGA-(l-y)fk(sub-KuE)) and its derivative in which the DOTAGA chelator was replaced by NODAGA (NODAGA-(l-y)fk(sub-KuE)), herein reported as DOTAGA-PSMA-I&T and NODAGA-PSMA-I&T, respectively, were labeled with 61Cu and compared with [68Ga]Ga-DOTAGA-PSMA-I&T, [68Ga]Ga-NODAGA-PSMA-I&T, [68Ga]Ga-PSMA-11, and [18F]PSMA-1007. In vitro (lipophilicity, affinity, cellular uptake, and distribution) and in vivo (PET/CT, biodistribution, and stability) studies were performed in LNCaP cells and xenografts. Human dosimetry estimates were calculated for [61Cu]Cu-NODAGA-PSMA-I&T. First-in-human imaging with [61Cu]Cu-NODAGA-PSMA-I&T was performed in a patient with metastatic prostate cancer. Results: [61Cu]Cu-DOTAGA-PSMA-I&T and [61Cu]Cu-NODAGA-PSMA-I&T were synthesized with radiochemical purity of more than 97%, at an apparent molar activity of 24 MBq/nmol, without purification after labeling. In vitro, natural Cu (natCu)-DOTAGA-PSMA-I&T and natCu-NODAGA-PSMA-I&T showed high affinity for PSMA (inhibitory concentration of 50%, 11.2 ± 2.3 and 9.3 ± 1.8 nM, respectively), although lower than the reference natGa-PSMA-11 (inhibitory concentration of 50%, 2.4 ± 0.4 nM). Their cellular uptake and distribution were comparable to those of [68Ga]Ga-PSMA-11. In vivo, [61Cu]Cu-NODAGA-PSMA-I&T showed significantly lower uptake in nontargeted tissues than [61Cu]Cu-DOTAGA-PSMA-I&T and higher tumor uptake (14.0 ± 5.0 percentage injected activity per gram of tissue [%IA/g]) than [61Cu]Cu-DOTAGA-PSMA-I&T (6.06 ± 0.25 %IA/g, P = 0.0059), [68Ga]Ga-PSMA-11 (10.2 ± 1.5 %IA/g, P = 0.0972), and [18F]PSMA-1007 (9.70 ± 2.57 %IA/g, P = 0.080) at 1 h after injection. Tumor uptake was also higher for [61Cu]Cu-NODAGA-PSMA-I&T at 4 h after injection (10.7 ± 3.3 %IA/g) than for [61Cu]Cu-DOTAGA-PSMA-I&T (4.88 ± 0.63 %IA/g, P = 0.0014) and [18F]PSMA-1007 (6.28 ± 2.19 %IA/g, P = 0.0145). Tumor-to-nontumor ratios of [61Cu]Cu-NODAGA-PSMA-I&T were superior to those of [61Cu]Cu-DOTAGA-PSMA-I&T and comparable to those of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 at 1 h after injection and increased significantly between 1 and 4 h after injection in most cases. Human dosimetry estimates for [61Cu]Cu-NODAGA-PSMA-I&T were similar to the ones reported for 18F-PSMA ligands. First-in-human imaging demonstrated multifocal osseous and hepatic metastases. Conclusion: [61Cu]Cu-NODAGA-PSMA-I&T is a promising PSMA radiotracer that compares favorably with [68Ga]Ga-PSMA-11 and [18F]PSMA-1007, while allowing delayed imaging.

Objective.This study aims to address the issue of long scan durations required by traditional graphical analysis methods, such as the Logan plot and its variant, the reversible equilibrium (RE) Logan plot, for dynamic PET imaging of tracer kinetics.Approach.We propose a relative RE Logan model that builds on the principles of the Logan plot and its variant to significantly reduce scan time without compromising the accuracy of tracer kinetics analysis. The model is supported by theoretical evidence and experimental validations, including two computer simulations and one clinical data analysis.Main results.The proposed model demonstrates a significant linear relationship between the variablexand the slopeDVTof the RE Logan plot, and the variablex\' and the slopeDVT\'of the relative RE Logan plot. The Pearson correlation coefficients (r) of the linear fitting of thex\' to thexequal 0.9849 in the simulated data and 0.9912 in the clinical data. Similarly, thervalues for the linear fitting ofDVT\'toDVTequal 0.9989 and 0.9988 in the simulated data, and 0.9954 in the clinical data.Significance.These results demonstrate the model\'s capability to maintain strong linear relationships and produce parametric images comparable to the traditional RE Logan plot, but with the considerable advantage of shorter scan durations. This innovation holds significant potential for enhancing the efficiency and feasibility of PET imaging in clinical settings.

UNASSIGNED: Prostate-specific membrane antigen (PSMA) PET/CT has become an unparalleled modality in the diagnosis of primary and recurrent prostatic adenocarcinoma, often revealing sites of disease that were previously invisible on conventional imaging. In this 78-year-old man with suspected prostate cancer recurrence, PSMA PET/CT revealed focal radiotracer uptake in the brain, which would ordinarily raise suspicion for metastases, but was a false positive in the setting of a recent stroke. Increased PSMA uptake has been reported in subacute infarcts and primary and secondary brain tumors. Careful history and comparison with prior imaging are vital to avoid false-positive diagnosis in such patients.

UNASSIGNED: Collateral circulation is often secondary to a regional thrombosis. This phenomenon can lead to the detection of misleading bone lesions on imaging and is a well-known source of false-positives. Here, we present 2 different tracers PET/CT images, 18 F-FDG and 18 F-choline, with collateral circulation but without obvious thrombosis. Both cases displayed bone uptake, which mimicked metastasis. However, clinical follow-up ruled out metastasis and revealed false-positive bone lesions related to collateral circulation, even in the lack of acute or chronic underlying thrombotic processes.

Despite the widespread use of hydrophilic building blocks to incorporate 18F and improve tracer pharmacokinetics, achieving effective leaving group-mediated nucleophilic 18F-fluorination in water (excluding 18F/19F-exchange) remains a formidable challenge. Here, we present a water-compatible SN2 leaving group-mediated 18F-fluorination method employing preconjugated \"AquaF\" (phosphonamidic fluorides) building blocks. Among 19 compact tetracoordinated pentavalent P(V)-F candidates, the \"AquaF\" building blocks exhibit superior water solubility, sufficient capacity for 18F-fluorination in water, and excellent in vivo metabolic properties. Two nitropyridinol leaving groups, identified from a pool of leaving group candidates that further enhance the precursor water solubility, enable 18F-fluorination in water with a 10-2 M-1 s-1 level reaction rate constant (surpassing the 18F/19F-exchange) at room temperature. With the exergonic concerted SN2 18F-fluorination mechanism confirmed, this 18F-fluorination method achieves ∼90% radiochemical conversions and reaches a molar activity of 175 ± 40 GBq/μmol (using 12.2 GBq initial activity) in saline for 12 \"AquaF\"-modified proof-of-concept functional substrates and small-molecule 18F-tracers. [18F]AquaF-Flurpiridaz demonstrates significantly improved radiochemical yield and molar activity compared to 18F-Flurpiridaz, alongside enhanced cardiac uptake and heart/liver ratio in targeted myocardial perfusion imaging, providing a comprehensive illustration of \"AquaF\" building blocks-assisted water-compatible SN2 18F-fluorination of small-molecule radiotracers.

This review focusses on the significance of fluorescent, phosphorescent labelling and tracking of extracellular vesicles (EVs) for unravelling their biology, pathophysiology, and potential diagnostic and therapeutic uses. Various labeling strategies, such as lipid membrane, surface protein, luminal, nucleic acid, radionuclide, quantum dot labels, and metal complex-based stains, are evaluated for visualizing and characterizing EVs. Direct labelling with fluorescent lipophilic dyes is simple but generally lacks specificity, while surface protein labelling offers selectivity but may affect EV-cell interactions. Luminal and nucleic acid labelling strategies have their own advantages and challenges. Each labelling approach has strengths and weaknesses, which require a suitable probe and technique based on research goals, but new tetranuclear polypyridylruthenium(II) complexes as phosphorescent probes have strong phosphorescence, selective staining, and stability. Future research should prioritize the design of novel fluorescent probes and labelling platforms that can significantly enhance the efficiency, accuracy, and specificity of EV labeling, while preserving their composition and functionality. It is crucial to reduce false positive signals and explore the potential of multimodal imaging techniques to gain comprehensive insights into EVs.

OBJECTIVE: Information about developed positron emission tomography (PET) tracers and obtained clinical PET images is publicly available in a database. However, findings regarding the kinetic parameters of PET tracers are yet to be summarized. Therefore, in this study, we created an open-access database of central nervous system (CNS) kinetic parameters in the healthy human brain for existing PET tracers (DOCK-PET).
METHODS: Our database includes information on the kinetic parameters and compounds of existing CNS-PET tracers. The kinetic parameter dataset comprises the analysis methods, VT, BPND, K parameters, relevant literature, and study details. The list of PET tracers and kinetic parameter information was compiled through keyword-based searches of PubMed and the Molecular Imaging and Contrast Agent Database (MICAD). The kinetic parameters obtained, including VT, BPND, and K parameters, were reorganized based on the defined brain anatomical regions. All data were rigorously double-checked before being summarized in Microsoft Excel and JavaScript Object Notation (JSON) formats.
RESULTS: Of the 247 PET tracers identified through searches using the PubMed and MICAD websites, the kinetic parameters of 120 PET tracers were available. Among the 120 PET tracers, compound structures with chemical and physical properties were obtained from the PubChem website or the ChemDraw software. Furthermore, the affinity information of the 104 PET tracers was gathered from PubChem or extensive literature surveys of the 120 PET tracers.
CONCLUSIONS: We developed a comprehensive open-access database, DOCK-PET, that includes both kinetic parameters of healthy humans and compound information for existing CNS-PET tracers.

Radiopharmaceuticals play a critical role in nuclear medicine, providing novel tools for specifically delivering radioisotopes for the diagnosis and treatment of cancers. As the starting point for developing radiopharmaceuticals, cancer-specific biomarkers are important and receive worldwide attention. This field in China is currently experiencing a rapid expansion, with multiple radiotracers targeting novel targets being developed and translated into clinical studies. This review provides a brief overview of the exploration of novel imaging targets, preclinical evaluation of their targeting ligands, and translational research in China from 2020 to 2023, for detecting cancer, guiding targeted therapy, and visualizing the immune microenvironment. We believe that China will play an even more important role in the development of nuclear medicine in the world in the future.