American journal of nuclear medicine and molecular imaging最新文献

Osteoporosis is a highly prevalent skeletal disease involving a pathophysiology of altered bone turnover. Positron emission tomography (PET)/computed tomography (CT) imaging with ¹⁸F-sodium fluoride (NaF) can visualize metabolic alterations in bone that precede clinical manifestations or structural alterations and thus may serve a role in the early detection and monitoring of osteoporosis. We present two non-oncological case reports demonstrating different metabolic changes in early and advanced disease stages as assessed by ¹⁸F-NaF PET/CT that cannot be appreciated by conventional structural imaging alone, supporting a potential clinical application of ¹⁸F-NaF PET/CT for early detection and monitoring of osteoporosis in the lumbar spine.

The U.S. Food and Drug Administration (FDA) has proposed a regulatory shift in the early-phase development of positron emission tomography (PET) radiopharmaceuticals, specifically regarding the requirement for animal-based dosimetry in first-in-human (FIH) studies. This editorial discusses the implications of the FDA's recent Advisory Committee briefing, which supports the omission of preclinical dosimetry under defined conditions for radiopharmaceuticals labeled with ¹⁸F, ¹¹C, ⁶⁸Ga, ⁶⁴Cu, ⁸²Rb, and ¹³N. The proposed policy reflects a shift toward a more streamlined, evidence-based approach to FIH studies while maintaining stringent standards for patient safety.

This symposium provided an extensive overview of emerging positron emission tomography (PET) tracers and targets for Alzheimer's disease (AD) and related dementias (ADRD), highlighting novel approaches for imaging neuroinflammation, neurotransmitter systems, mitochondrial dysfunction, and proteinopathies. Key developments included the harmonization of PET data across cohorts, new tau and alpha-synuclein tracers, and critical advancements in understanding neurodegenerative disease heterogeneity through integrated imaging, genetic, and pathological studies.

Radiolabeled folate derivatives have been extensively investigated for positron emission tomography (PET) imaging of ovarian cancer due to the frequent overexpression of folate receptor α (FRα). However, clinical translation has been hindered, at least in part, by suboptimal tumor uptake of FRα-targeted radiotracers. In this study, we developed and characterized a ⁶⁸Ga-labeled heterodimeric radiotracer, ⁶⁸Ga-folate-KR, designed to concurrently target FRα and human epidermal growth factor receptor 2 (HER2), another receptor commonly overexpressed in ovarian cancer. Transcriptomics analysis confirmed the co-upregulation of FOLR1 and HER2 in ovarian cancer tissues relative to normal ovarian tissue, supporting the rationale for dual-receptor targeting. In vitro binding assays demonstrated specific binding of ⁶⁸Ga-folate-KR to both receptors. PET imaging and biodistribution studies in SKOV3 tumor-bearing mice revealed significantly enhanced tumor uptake and improved tumor-to-nontumor contrast compared to the monomeric radiotracers ⁶⁸Ga-folate and ⁶⁸Ga-KR. Competitive blocking experiments further confirmed the in vivo dual-receptor targeting capability of ⁶⁸Ga-folate-KR. Collectively, our results highlight that ⁶⁸Ga-folate-KR enables more sensitive PET detection of ovarian cancer xenografts. With further optimization, dual-receptor-targeted radiotracers hold promise for clinical translation in both lesion detection and therapy response monitoring in ovarian cancer.

O-(2-[¹⁸F]Fluoroethyl)- _L -tyrosine ([¹⁸F]FET) is a promising amino acid PET tracer for assessment of malignant brain tumors. Herein, we report optimized production of [¹⁸F]FET for clinical use on two commercial radiochemistry systems: Sofie ELIXYS and GE FASTlab 2. While the Sofie ELIXYS procedure requires high performance liquid chromatography (HPLC) purification, the GE FASTlab 2 method uses solid-phase extraction (SPE) purification. In both cases, [¹⁸F]FET met release specifications for clinical investigation laid out in the United States Pharmacopeia (USP) and/or European Pharmacopeia (Ph. Eur.). The radiochemical yield of [¹⁸F]FET was 35-55% and 30-55% decay corrected to start of synthesis (SOS) for Sofie ELIXYS and GE FASTlab 2, respectively. The overall synthesis time was 75-85 and 70-80 min from SOS for Sofie ELIXYS and GE FASTlab 2, respectively. The radiochemical purity was > 99%, and the molar activity (A_m) was 340-464 GBq/µmol at end of synthesis (EOS).

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 (Trodelvy^TM), 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.