Inflammation is a major contributor to human mortality, accounting for over 50% of deaths worldwide. Therefore, there is an urgent need for early and accurate diagnostic methods. PET imaging targeting leukocyte common antigen CD45 presents a promising approach for detecting inflammation and monitoring therapeutic responses.
Trophoblast cell surface antigen 2 (TROP2) represents an ideal target in cancer diagnosis and therapy, particularly in antibody-drug conjugate (ADC) treatments. Several TROP2-targeted ADCs have been used for the treatment of end-stage metastatic cancers, demonstrating promising therapeutic efficacy. Research has shown that the efficacy of TROP2-ADCs is closely correlated with TROP2 expression levels, highlighting the potential of TROP2 expression as a key factor for patient stratification and selection, which could significantly predict the therapy response and therefore enhance treatment outcomes. Currently, immunohistochemistry (IHC) is the gold standard for detecting TROP2 expression, although it has certain limitations. Non-invasive molecular imaging techniques offer the potential to overcome these limitations, providing valuable guidance for subsequent treatment strategies. The development of immuno-Positron Emission Tomography (immunoPET) technologies, including radiolabeled monoclonal antibodies, nanobodies, peptides and small molecules, have made the non-invasive measurement of TROP2 expression feasible. TROP2-targeted molecular imaging represents a promising frontier for precision oncology, despite existing challenges in clinical translation. This review systematically summarizes the research progress in TROP2-targeted molecular imaging for tumor diagnosis and therapy, while discussing innovative approaches to overcome current technical limitations and accelerate clinical implementation.
Background: Head and neck cancer (HNC) patients frequently develop post-radiation maxillary sinusitis. This study investigated how different radiation therapy (RT) modalities, photon, proton, and mixed photon/proton RT, affect maxillary sinus inflammation, using 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT).
Methods: Seventy-seven HNC patients treated with RT (30 with photon, 20 with proton, and 27 with mixed photon/proton RT) underwent FDG-PET/CT imaging before and 3 months after treatment. Demographic information, tumor location, chemotherapy details, radiation dose (cGy), and post-radiation sinusitis ratings (scale 0-2) were collected. The mean standardized uptake value (SUVmean) of the maxillary sinus was measured by a radiologist with two years of experience using manually delineated regions of interest. Parametric paired t-tests were used to compare pre- and post-treatment SUVmeans for each RT modality. Pre-minus-post-treatment changes in SUVmean (ΔSUVmean) between RT modalities were compared using independent t-tests. Correlation between radiation dose and ΔSUVmean and correlation between ΔSUVmean and clinical sinusitis scores were assessed using Pearson correlation analysis.
Results: Photon RT was associated with a statistically significant increase in maxillary sinus SUVmean post-treatment (+14.32%, P = 0.0324), while proton RT and mixed photon/proton RT did not result in significant changes (-3.39%, P = 0.6549 and -5.33%, P = 0.4541, respectively). A significant difference was found between photon and mixed photon/proton RT (P = 0.0444), whereas the difference between photon and proton RT approached significance (P = 0.0790). Clinical inflammation ratings were highest for photon therapy (average 0.97), followed by mixed therapy (0.78), then proton therapy (0.65), though these differences were not statistically significant.
Conclusion: Our findings demonstrate that photon RT leads to significant increases in maxillary sinus SUVmean as measured by FDG-PET/CT, while proton and mixed photon/proton RT do not show statistically significant changes. These preliminary results suggest that proton-based radiation modalities may be associated with reduced maxillary sinus inflammatory activity compared to photon RT alone, though larger studies with longer follow-up are needed to establish clinical significance and patient outcomes.
Trop2 is overexpressed in various tumors and serves as a key biomarker. Targeted immunoPET ligands, mainly developed from Trop2 monoclonal antibodies and nanobodies, provide the landscape of heterogeneous expression of Trop2 in tumors, which has great potential in improving accuracy of cancer diagnosis and staging, as well as decision-making in therapy.
Purpose: The Trop2-targeting antibody-drug conjugate (ADC), sacituzumab govitecan (TrodelvyTM), demonstrates significant therapeutic efficacy in targeting Trop2-expressing tumors. In this study, we utilized immunoPET imaging to assess Trop2 expression in bladder cancer models using [89Zr]Zr-DFO-Trodelvy.
Materials and methods: Trop2 expression levels in bladder cancer cell lines were measured using flow cytometry and immunofluorescence staining. Radiolabeling of DFO-Trodelvy with 89Zr was carried out in Na2CO3 buffer at pH 7 (37°C, 1.5 h). ImmunoPET imaging with [89Zr]Zr-DFO-Trodelvy was performed at multiple time points to evaluate in vivo targeting. Additionally, tumor tissues from tumor-bearing mice were analyzed by immunofluorescence.
Results: The radiochemical yield of [89Zr]Zr-DFO-Trodelvy was >90%, with radiochemical purity exceeding 99%. Trop2 expression was high in HT1376 cells and low in T24 cells. ImmunoPET imaging demonstrated effective visualization of tumors in HT1376 models as early as 6 h post-injection, with tumor uptake reaching peak at 48 h (16.33 ± 0.90 %ID/g), followed by a gradual decline. In contrast, T24 tumors showed significantly lower uptake (6.20 ± 0.99 %ID/g, P = 0.0005). Co-injection with 2 mg of unlabeled Trodelvy significantly reduced tumor uptake in HT1376 models (4.50 ± 0.51 %ID/g, P = 0.0004), confirming target specificity. At 48 h, a high tumor-to-background ratio was observed, indicating selective accumulation in tumor tissue.
Conclusions: [89Zr]Zr-DFO-Trodelvy enables precise immunoPET imaging of bladder cancer models with high Trop2 expression, demonstrating specific and sustained tumor accumulation. These findings highlight the potential of this imaging approach for the noninvasive assessment of Trop2 expression.
Gallium-68 labeled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI-04) can be visualized just 15 min post-injection. However, the appearance of imaging at 15 and 60 min remains unclear. This study aimed to explore the relationship between quantitative values in [68Ga]Ga-FAPI-04 PET, specifically at 15 and 60 minutes post-injection, in patients with various tumor. We enrolled 30 patients with cancer who underwent [68Ga]Ga-FAPI-04 PET/CT scan between January 2021 and February 2025 at our institute. Image acquisition was performed using a PET/CT scanner at 15 min and 60 min after [68Ga]Ga-FAPI-04 injection. The maximum, mean and peak standardized uptake value (SUVmax, SUVmean and SUVpeak), tumor-to-liver ratio (TLR), and uptake tumor volume (UTV) were measured in the region of interest of the target lesion, liver SUVmean (SUVliver) was also measured. Correlation coefficients of the between-image variables were evaluated by Spearman's rank correlation test. Agreement between the variables was evaluated by Bland-Altman plots with 95% limits of agreement. The SUVmax, SUVmean, SUVpeak and UTV in tumors of all examinations were decreased from 15 min to 60 min. The SUVmax, SUVmean, SUVpeak, TLR, and UTV at 15 min and 60 min were highly correlated (rs = 0.945, 0.949, 0.959, 0.943, and 0.958; P < 0.001). The 95% limits of agreement ranged from -27.8 to 29.1 with a mean of 0.7 and -24.1 to 29.5 with a mean of 2.7 for SUVmax and SUVmean, respectively. Other PET metrics demonstrated that all limits are above ± 30% between 15 min and 60 min. We observed a high correlation between the quantitative values at 15 min and 60 min. Meanwhile, 15 min and 60 min [68Ga]Ga-FAPI-04 PET SUVmax and SUVmean have clinically acceptable reproducibility, and 15 min scan is feasible for all patients, but SUVpeak, TLR and UTV should not be used interchangeably.
Phosphodiesterase 4B (PDE4B) is an enzyme that hydrolyzes cyclic adenosine monophosphate (cAMP), a critical signaling molecule involved in various cellular processes. Dysregulated PDE4B activity has been implicated in psychiatric diseases like depression and schizophrenia. In this report, a PDE4B-targeted PET tracer, [18F]PF-06445974, was synthesized using an automated synthesis module. [18F]PF-06445974 demonstrated high brain specificity, robust uptake, and excellent stability. In vivo metabolic studies confirmed that its radioactive metabolites did not cross the blood-brain barrier, and no abnormal bone uptake was observed in PET imaging. Furthermore, PET studies and quantitative autoradiography revealed significantly increased expression of PDE4B in the hippocampus and cortex of depression model rats compared to normal controls. The findings highlight the potential of in vivo PDE4B PET imaging as a valuable tool for monitoring PDE4B changes in depression, providing insights into its pathophysiological processes and paving the way for clinical translational research in this domain.
Objective: The heterogeneity of gastric cancer (GC) poses significant challenges for the detection capabilities of monomeric fibroblast activation protein inhibitor (FAPI) tracers, particularly in cases with low FAP expression. To address this limitation, a dual-target heterodimeric radiotracer, 18F-FAPI-42-RGD, was designed to target both FAP and integrin αvβ3. This study aimed to evaluate the efficacy of 18F-FAPI-42-RGD in GC models and compare its performance with the mono-specific radiotracer, 18F-FAPI-42.
Methods: 18F-FAPI-42-RGD was synthesized, and its radiochemical properties and stability were assessed. Micro-PET imaging and biodistribution studies were conducted in BALB/C nude mice bearing MKN-45, N87-18.2, NUGC4 tumors, and GC patient-derived xenografts (PDX). The results were compared with those obtained from 18F-FAPI-42.
Results: 18F-FAPI-42-RGD demonstrated excellent stability in saline and fetal bovine serum (FBS) for at least 2 hours. Compared to 18F-FAPI-42, 18F-FAPI-42-RGD exhibited significantly enhanced tumor uptake in MKN-45, N87-18.2, NUGC4, and GC-PDX tumors at all time points. Biodistribution studies revealed that 18F-FAPI-42-RGD had markedly higher tumor uptake in GC models compared to 18F-FAPI-42, particularly in the MKN-45, N87-18.2, and GC-PDX tumor models. The uptake of 18F-FAPI-42-RGD in these tumors was significantly greater than that of 18F-FAPI-42 (4.97 ± 1.36 vs. 2.18 ± 1.26, 7.02 ± 0.97 vs. 2.34 ± 0.11, and 4.49 ± 1.29 vs. 1.09 ± 0.46 %ID/g in MKN-45, N87-18.2, and GC-PDX, respectively, at 4 h post-injection).
Conclusion: The dual-targeting PET tracer 18F-FAPI-42-RGD demonstrated significantly enhanced tumor uptake in GC models, along with a clearer background compared to 18F-FAPI-42. This indicates its superior diagnostic performance, suggesting its potential for clinical translation in the imaging and diagnosis of GC.
To evaluate the safety and VEGFR-3 imaging effects of [68Ga]Ga-NOTA-(TMVP1)2 in ovarian cancer patients. 13 patients with ovarian cancer were recruited and underwent radionuclide imaging with [68Ga]Ga-NOTA-(TMVP1)2. The safety of [68Ga]Ga-NOTA-(TMVP1)2 was assessed in vivo (including vital signs, biochemical indices, ECG, allergic reactions, etc.) and its imaging effect on VEGFR-3 was explored. A total of 1 patient with primary ovarian cancer and 12 patients with recurrent ovarian cancer, with an age range of 41-54 years, were included in the study. 13 ovarian cancer patients had a total of 49 18F-FDG-positive lesions, 63.3% of which were positive for [68Ga]Ga-NOTA-(TMVP1)2. The higher expression of VEGFR-3 in [68Ga]Ga-NOTA-(TMVP1)2-positive ovarian cancer lesions was found by immunohistochemical staining, which was positively correlated. Meanwhile, [68Ga]Ga-NOTA-(TMVP1)2 is a safe radiotracer as no significant side effects have been found in the human. In conclusion, [68Ga]Ga-NOTA-(TMVP1)2 enables precise molecular imaging of VEGFR-3 in ovarian cancer patients with a favourable safety profile, providing a new tool for the in vivo assessment of VEGFR-3 in ovarian cancer.
Radiopharmaceuticals targeting fibroblast activation protein (FAP) have rapidly emerged as innovative agents for cancer imaging and therapy. By selectively binding to cancer-associated fibroblasts (CAFs), radiolabeled FAP inhibitors (FAPIs) enable high-contrast PET/CT imaging across diverse tumor types. This article highlights recent advances in FAPI PET/CT imaging, with particular focus on the influence of multivalency effect in radiotracer development.
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