American journal of nuclear medicine and molecular imaging最新文献

Meningiomas are the most common primary intracranial tumors, with treatment involving resection and radiation therapy. However, therapeutic options are limited for recurrent or progressive disease, particularly in higher World Health Organization (WHO) grade tumors. Somatostatin receptor (SSTR) expression in meningiomas has opened new therapeutic opportunities as the differential SSTR2 overexpression permits molecular targeting using radiolabeled somatostatin analogs. PRRT offers promising therapeutic efficacy in select meningioma patients, with clinical responses strongly correlated to WHO tumor grade and SSTR expression levels. Combining SSTR PET imaging, to evaluate receptor density, with radiomic analysis can reveal tumor heterogeneity patterns and quantitative imaging features that can guide clinical decision-making and monitor treatment response. Integrating machine learning and artificial intelligence (AI) into clinical workflows offer novel approaches to apply quantitative SUV parameters, image texture features, and histopathologic data in order to identify patients with WHO grade II and III meningiomas at greater risk of tumor recurrence. Given the heterogeneity in imaging and treatment protocols across institutions and the limited number of PRRT-treated meningioma cohorts, future research should prioritize prospective, multicenter studies that integrate histologic and molecular imaging data to refine patient selection strategies and establish PRRT's role within personalized, precision cancer treatment paradigms.

Terbium-161 (¹⁶¹Tb) is emerging as a promising theranostic radionuclide for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) in metastatic castration-resistant prostate cancer (mCRPC). Compared with lutetium-177 (¹⁷⁷Lu), ¹⁶¹Tb emits additional high-linear energy transfer Auger and internal conversion electrons, enabling superior tumor cell kill in micrometastatic disease. Early clinical studies demonstrate favorable safety, dosimetry, and efficacy profiles for ¹⁶¹Tb-labeled PSMA ligands. Ongoing trials and production advancements are critical to fully realizing the therapeutic potential of ¹⁶¹Tb-based RLT.

The purpose of this study is to evaluate the PSMA PET imaging parameters in association with outcomes among patients with oligorecurrent prostate cancer. This retrospective single-center study included 101 patients (median age 71; interquartile range 65-75) with biochemically recurrent prostate cancer who underwent PSMA PET between May 2021 and May 2022, revealing 5 or fewer sites of metastases (oligometastatic disease). Multiple variables including maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean), and molecular tumor volume (MTV) were measured and analyzed on a per-patient basis, along with total MTV and molecular tumor burden (MTB). Multivariable Cox proportional-hazards regression models were used to identify factors associated with progression-free survival (PFS). PSMA PET revealed a total of 216 lesions across all patients, of which 134 (62.0%) involved the lymph nodes and 56 (25.9%) involved the bone. A total of 61 (60.4%) patients received combined metastasis-directed and hormone therapy, and 40 (39.6%) received hormone therapy only. The median subsequent follow-up from PSMA PET detection of oligorecurrent disease was 18.2 months (IQR 10.3-25.0). MTV on PSMA PET was associated with worse PFS (hazard ratio: 1.05, 95% CI 1.00-1.11; P = 0.04). Molecular tumor volume on PSMA PET is associated with worse clinical outcomes in patients with oligorecurrent prostate cancer.

Poly(ADP-Ribose) Polymerase 1 (PARP1) is a key DNA repair enzyme and therapeutic target in cancer, with overexpression observed in several cancers, including basal cell carcinoma (BCC). Conventional diagnostic methods for BCC lack specificity and are invasive, highlighting the need for noninvasive alternatives. PARP-targeted molecular imaging, particularly with fluorescence probes, has shown strong potential for tumor detection and real-time visualization. PARPi-FL, a fluorescent derivative of Olaparib, enables rapid, specific, and high-contrast imaging of BCC in preclinical and ex vivo human studies. Optimized application protocols confirm its safety and translational promise for noninvasive diagnosis and image-guided surgery.

T-cell activation within the tumor microenvironment is a key determinant of response to immunotherapy, yet current biomarkers fail to capture its spatial and temporal dynamics. Traditional assays such as PD-L1 immunohistochemistry, tumor mutational analysis, and circulating cytokine profiling offer static or systemic snapshots that inadequately reflect localized immune engagement. Positron emission tomography (PET) provides a unique opportunity to visualize these processes in vivo. Among emerging tracers, CXCL9-targeted imaging stands out as a promising approach to quantify IFNγ-driven T-cell activation and recruitment. Jacobson et al. report the development of [¹⁸F]F-h2A12, a high-affinity nanobody PET tracer specific for CXCL9. Preclinical studies demonstrate robust uptake in CXCL9-expressing tumors, close correlation with intratumoral immune activation, and clear distinction from blood-based biomarkers. Compared with existing immune PET tracers that target cytotoxic enzymes, soluble cytokines, or surface activation markers, CXCL9 imaging offers an advantageous balance of specificity, localization, and functional relevance. By visualizing the chemokine gradients that govern T-cell trafficking, CXCL9 PET could serve as an early, noninvasive biomarker of immunotherapy response and a powerful tool for guiding adaptive treatment strategies.

The metabotropic glutamate receptor 3 (mGluR3) is a G-protein-coupled receptor (GPCR) involved in modulating glutamatergic neurotransmission and maintaining neural homeostasis. By inhibiting adenylyl cyclase activity, mGluR3 negatively modulates the activity of adenylyl cyclase via Gi/o protein coupling, reducing cyclic AMP (cAMP) levels and modulating downstream signaling pathways. Dysfunction of mGluR3 is associated with a range of neurological and psychiatric disorders, including depression, autism, cognitive impairment, bipolar affective disorder, schizophrenia, and neurodegenerative diseases. Despite its therapeutic relevance, no selective mGluR3 positron emission tomography (PET) radioligand is currently available to image this target in vivo. In this study, we report the radiosynthesis and preclinical evaluation of [¹⁸F]VU6010572 - a novel PET tracer based on a therapeutical drug candidate. VU6010572 exhibits potent binding affinity (IC₅₀ = 39.9 nM) and exceptional selectivity (>100-fold over other mGluR subtypes). Radiolabeling with fluorine-18 yielded [¹⁸F]VU6010572 with high radiochemical yield (48%, decay-corrected) and molar activity (59 GBq/µmol). While in vitro autoradiography demonstrated heterogeneous brain distribution, dynamic PET imaging in rodents revealed reasonable brain uptake in vivo yet modest binding specificity and rapid brain washout. While these findings support the potential of [¹⁸F]VU6010572 as a lead structure, further medicinal chemistry optimization is warranted to enhance the metabolic and pharmacokinetic properties.

DLL3 is overexpressed on the cell surface of NENs, such as SCLC and NEPC, but notably restricted to cytoplasm with low expression levels in normal adult human tissues. Several radioligands have been developed by targeting DLL3 for immunoPET or radioimmunotherapy use. These ligands hold great promise for mapping the heterogeneous DLL3 expression in neuroendocrine tumors and guiding the DLL3-directed therapeutic strategies.

Purpose: To refine the optimal PRIMARY score thresholds across different PSA ranges, enhancing diagnostic accuracy for clinically significant prostate cancer (csPCa).

Methods: The study retrospectively analyzed 373 patients who underwent PSMA PET/CT scans for suspected csPCa between June 2021 and December 2023. The diagnostic efficacy of PRIMARY score was independently assessed using 68Ga-PSMA PET/CT. Receiver-operating characteristic curve analysis was used to estimate the diagnostic performance. The diagnostic efficacy of the PRIMARY score with different thresholds in different PSA ranges was also calculated and compared.

Results: The PRIMARY score maintains high diagnostic accuracy either in group of PSA ≤ 20 ng/mL or PSA > 20 ng/mL, with an AUC exceeding 0.8 at appropriate thresholds. Notably, in patients with PSA > 20 ng/mL, a PRIMARY score threshold of 4 demonstrated enhanced diagnostic accuracy compared to a threshold of 3, significantly improving specificity from 70.6% to 91.2% while maintaining high sensitivity (from 99.2% to 98.4%). Consequently, 91.2% (31/34) patients could avoid unnecessary biopsies, at the expense of missing 1.6% (2/125) of csPCa cases.

Conclusion: Across different PSA ranges, the PRIMARY score based on ⁶⁸Ga-PSMA PET/CT imaging is useful in the diagnosis of csPCa. A threshold of 3 for PSA ≤ 20 ng/mL and a threshold of 4 for 20 ng/mL < PSA ≤ 50 ng/mL respectively demonstrated favorable diagnostic performance.

O-GlcNAcase (OGA) is a key enzyme involved in regulating the dynamic cycling of O-GlcNAc modifications on intracellular proteins. OGA has emerged as a promising therapeutic target for neurodegenerative diseases, including Alzheimer's disease. In this report, we present the radiosynthesis and preclinical assessment of a novel carbon-11 labeled positron emission tomography (PET) radioligand [¹¹C]1 (codenamed OGA-2504) targeting OGA. The aminopyrimidine-based compound 1 and its corresponding desmethyl precursor were synthesized efficiently with good chemical yields. Radiosynthesis of [¹¹C]1 was accomplished via ¹¹C-methylation, yielding an 8% decay-corrected radiochemical yield with high purity (>98%) and high molar activity (92.5 GBq/µmol). [¹¹C]1 exhibited moderate lipophilicity (LogD = 2.11) and excellent in vivo stability in serum. However, preliminary PET imaging revealed low brain uptake and slow clearance of [¹¹C]1 in mice, suggesting a need for further structural optimization to enhance brain penetration.