European Journal of Nuclear Medicine and Molecular Imaging最新文献

Purpose: Respiratory motion (RM) significantly impacts image quality in thoracoabdominal PET/CT imaging. This study introduces a unified data-driven respiratory motion correction (uRMC) method, utilizing deep learning neural networks, to solve all the major issues caused by RM, i.e., PET resolution loss, attenuation correction artifacts, and PET-CT misalignment.

Methods: In a retrospective study, 737 patients underwent [¹⁸F]FDG PET/CT scans using the uMI Panorama PET/CT scanner. Ninety-nine patients, who also had respiration monitoring device (VSM), formed the validation set. The remaining data of the 638 patients were used to train neural networks used in the uRMC. The uRMC primarily consists of three key components: (1) data-driven respiratory signal extraction, (2) attenuation map generation, and (3) PET-CT alignment. SUV metrics were calculated within 906 lesions for three approaches, i.e., data-driven uRMC (proposed), VSM-based uRMC, and OSEM without motion correction (NMC). RM magnitude of major organs were estimated.

Results: uRMC enhanced diagnostic capabilities by revealing previously undetected lesions, sharpening lesion contours, increasing SUV values, and improving PET-CT alignment. Compared to NMC, uRMC showed increases of 10% and 17% in SUV_max and SUV_mean across 906 lesions. Sub-group analysis showed significant SUV increases in small and medium-sized lesions with uRMC. Minor differences were found between VSM-based and data-driven uRMC methods, with the SUV_max was found statistically marginal significant or insignificant between the two methods. The study observed varied motion amplitudes in major organs, typically ranging from 10 to 20 mm.

Conclusion: A data-driven solution for respiratory motion in PET/CT has been developed, validated and evaluated. To the best of our knowledge, this is the first unified solution that compensates for the motion blur within PET, the attenuation mismatch artifacts caused by PET-CT misalignment, and the misalignment between PET and CT.

Purpose: Accurate diagnosis and staging of prostate cancer are crucial to improving patient care. Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography with computed tomography (PET/CT) imaging has demonstrated superiority for initial staging and restaging in patients with prostate cancer. Referring physicians and PET/CT readers must agree on a consistent communication method and application of information derived from this imaging modality. While several guidelines have been published, a single PSMA PET/CT reporting template has yet to be widely adopted. Based on the consensus from community and academic physicians, we developed a standardized PSMA PET/CT reporting template for radiologists and nuclear medicine physicians to report and relay key imaging findings to referring physicians. The aim was to improve the quality, clarity, and utility of imaging results reporting to facilitate patient management decisions.

Methods: Based on community and expert consensus, we developed a standardized PSMA PET/CT reporting template to deliver key imaging findings to referring clinicians.

Results: Core category components proposed include a summary of any prior treatment history; presence, location, and degree of PSMA radiopharmaceutical uptake in primary and/or metastatic tumor(s), lesions with no uptake, and incidentally found lesions with positive uptake on PET/CT.

Conclusions: This article provides recommendations on best practices for standardized reporting of PSMA PET/CT imaging. The generated reporting template is a proposed supplement designed to educate and improve data communication between imaging experts and referring physicians.

Purpose: Somatostatin Receptor 2 (SSTR2)-targeted radiopharmaceutical [⁶⁸Ga]Ga-DOTATATE has potential advantages in the diagnosis of nasopharyngeal carcinoma (NPC). This study introduces a novel long-lasting SSTR2 analogue, LNC1010, based on DOTATATE, a truncated Evans blue-binding moiety, and a polyethylene-glycol linker. We hypothesised that peptide receptor radionuclide therapy (PRRT) is more effective with [¹⁷⁷Lu]Lu-LNC1010 than with [¹⁷⁷Lu]Lu-DOTATATE in treating metastatic NPC.

Methods: We assessed binding characteristics of LNC1010 in vitro using C666-1 NPC cells and in-vivo pharmacokinetics of [⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-LNC1010 in C666-1 NPC xenografts via PET and SPECT imaging, biodistribution studies, and PRRT, and compared them with [⁶⁸Ga]Ga/[¹⁷⁷Lu] Lu-labelled DOTATATE. Furthermore, a proof-of-concept approach for imaging and therapy was conducted in a patient with metastatic NPC.

Results: LNC1010 exhibited strong uptake and specific affinity for SSTR2 in C666-1 NPC cells. PET and SPECT imaging demonstrated higher uptake and longer tumour retention of [⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-LNC1010 than [⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-DOTATATE in C666-1 NPC xenografts, indicating its suitability for PRRT applications in NPCs. Biodistribution studies confirmed the higher uptake and prolonged retention of [¹⁷⁷Lu]Lu-LNC1010 than [¹⁷⁷Lu]Lu-DOTATATE. In preclinical PRRT studies, [¹⁷⁷Lu]Lu-LNC1010 showed greater inhibition of tumour growth in C666-1 NPC xenografts than [¹⁷⁷Lu]Lu-DOTATATE. In a subsequent pilot clinical study, PRRT with [¹⁷⁷Lu]Lu-LNC1010 achieved favourable therapeutic and negligible side effects in a patient with metastatic NPC.

Conclusion: [¹⁷⁷Lu]Lu-LNC1010 demonstrated increased tumour uptake and prolonged retention in SSTR2-positive NPCs, with superior anti-tumour efficacy to that of [¹⁷⁷Lu]Lu-DOTATATE in preclinical studies. These findings suggest that PRRT with [¹⁷⁷Lu]Lu-LNC1010 is a promising treatment for advanced NPC, extending the clinical scope of PRRT beyond neuroendocrine tumours.

Introduction: Accurate diagnosis of liver fibrosis is crucial for preventing cirrhosis and liver tumors. Liver fibrosis is driven by activated hepatic stellate cells (HSCs) with elevated CD44 expression. We developed hyaluronic acid (HA)-coated gadolinium-based nanoprobes to specifically target CD44 for diagnosing liver fibrosis using T1-weighted magnetic resonance imaging (MRI).

Materials and methods: NaGdF₄ nanoparticles (NPs) were synthesized via thermal decomposition and modified with polyethylene glycol (PEG) to obtain non-targeting NaGdF₄@PEG NPs. These were subsequently coated with HA to target HSCs, resulting in liver fibrosis-targeting NaGdF₄@PEG@HA nanoprobes. Characterization includedd transmission electron microscopy and X-ray diffraction. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8). Internalization of NaGdF₄@PEG@HA nanoprobes by mouse HSCs JS1 cells via ligand-receptor interaction was observed using flow cytometry and confocal laser scanning microscopy (CLSM). Liver fibrosis was induced in C57BL/6 mice using a methionine-choline deficient (MCD) diet. MRI performance and nanoprobe distribution in fibrotic and normal livers were analyzed using a GE Discovery 3.0T MR 750 scanner.

Results: NaGdF₄@PEG@HA nanoprobes exhibited homogeneous morphology, low toxicity, and a high T1 relaxation rate (7.645 mM⁻¹s⁻¹). CLSM and flow cytometry demonstrated effective phagocytosis of NaGdF₄@PEG@HA nanoprobes by JS1 cells compared to NaGdF₄@PEG. MRI scans revealed higher T1 signals in fibrotic livers compared to normal livers after injection of NaGdF₄@PEG@HA. NaGdF₄@PEG@HA demonstrated higher targeting ability in fibrotic mice.

Conclusions: NaGdF₄@PEG@HA nanoprobes effectively target HSCs with high T1 relaxation rate, facilitating efficient MRI diagnosis of liver fibrosis.

Purpose: While immunotherapy has revolutionized the oncology field, variations in therapy responsiveness limit the broad applicability of these therapies. Diagnostic imaging of immune cell, and specifically CD8⁺ T cell, dynamics could allow early patient stratification and result in improved therapy efficacy and safety. In this study, we report the development of a nanobody-based immunotracer for non-invasive SPECT and PET imaging of human CD8⁺ T-cell dynamics.

Methods: Nanobodies targeting human CD8β were generated by llama immunizations and subsequent biopanning. The lead anti-human CD8β nanobody was characterized on binding, specificity, stability and toxicity. The lead nanobody was labeled with technetium-99m, gallium-68 and copper-64 for non-invasive imaging of human T-cell lymphomas and CD8⁺ T cells in human CD8 transgenic mice and non-human primates by SPECT/CT or PET/CT. Repeated imaging of CD8⁺ T cells in MC38 tumor-bearing mice allowed visualization of CD8⁺ T-cell dynamics.

Results: The nanobody-based immunotracer showed high affinity and specific binding to human CD8 without unwanted immune activation. CD8⁺ T cells were non-invasively visualized by SPECT and PET imaging in naïve and tumor-bearing mice and in naïve non-human primates with high sensitivity. The nanobody-based immunotracer showed enhanced specificity for CD8⁺ T cells and/or faster in vivo pharmacokinetics compared to previous human CD8-targeting immunotracers, allowing us to follow human CD8⁺ T-cell dynamics already at early timepoints.

Conclusion: This study describes the development of a more specific human CD8⁺ T-cell-targeting immunotracer, allowing follow-up of immunotherapy responses by non-invasive imaging of human CD8⁺ T-cell dynamics.

Purpose: TMPRSS2:ERG gene fusion negatively regulates PSMA expression in prostate adenocarcinoma (PCa) cell lines. Therefore, immunohistochemical (IHC) ERG expression, a surrogate for an underlying ERG rearrangement, and PSMA expression patterns in radical prostatectomy (RPE) specimens of primary PCa, including corresponding PSMA-PET scans were investigated.

Methods: Two cohorts of RPE samples (total n=148): In cohort #1 (n=62 patients) with available RPE and preoperative [⁶⁸Ga]Ga-PSMA-11 PET, WHO/ISUP grade groups, IHC-ERG (positive vs. negative) and IHC-PSMA expression (% PSMA-negative tumour area, PSMA_%neg) were correlated with the corresponding SUV_max. In the second cohort #2 (n=86 patients) including RPE only, same histopathological parameters were evaluated.

Results: Cohort #1: PCa with IHC-ERG expression (35.5%) showed significantly lower IHC-PSMA expression and lower SUV_max values on the corresponding PET scans. Eight of 9 PCa with negative PSMA-PET scans had IHC-ERG positivity, and confirmed TMPRSS2::ERG rearrangement. In IHC-PSMA positive PCa, IHC-ERG positivity was significantly associated with lower SUV_max values. In cohort #2, findings of higher IHC-PSMA_%neg and IHC-ERG expression was confirmed with only 0-10% PSMA_%neg tumour areas in IHC-ERG-negative PCa.

Conclusion: IHC-ERG expression is significantly associated with more heterogeneous and lower IHC-PSMA tissue expression in two independent RPE cohorts. There is a strong association of ERG positivity in RPE tissue with lower [⁶⁸Ga]Ga-PSMA-11 uptake on corresponding PET scans. Results may serve as a base for future biomarker development to enable tumour-tailored, individualized imaging approaches.

Background: The nucleus basalis of Meynert (NBM) is known to play a crucial role in the development and pathogenesis of Alzheimer's Disease (AD), particularly the cholinergic system within the NBM. However, the relationship between synaptic loss in the NBM and the clinical profile of AD remains unclear.

Methods: In our study, we included 44 Aβ-negative normal controls (CN) and 76 Aβ-positive participants with cognitive impairment (CI). All participants underwent structural and diffusion magnetic resonance imaging (MRI), as well as positron emission tomography (PET) imaging to measure synaptic vesicle glycoprotein 2 A (SV2A) levels (Trial registration: NCT05623124. Registered 21 November 2022). The SV2A standardized uptake value ratios (SUVR) distribution in the NBM of CN participants was used as the reference norm. We investigated the association between NBM synaptic density and clinical performance, traditional AD biomarkers, and white matter tracts that passed the NBM.

Results: Participants with cognitive impairment (CI) who had NBM synaptic density below 1.5 standard deviations (SD) or 0.5 SD of the norm exhibited worse cognitive performance compared to cognitively normal (CN) individuals. Crucially, the extent of deviation in synaptic density from the norm was directly proportional to the severity of cognitive impairment and neurodegeneration biomarkers. Furthermore, among patients with cognitive impairment, synaptic loss in the NBM was associated with potential impairment in the density and organization of neurites within the white matter tracts connected to the NBM. Finally, neurite density index in the medial tracts may play a mediating role in the relationship between NBM synaptic density and MMSE scores.

Conclusion: The extent that synaptic density in NBM deviated from the norm suggested the extent of worse cognitive performance and severe neurodegeneration. Furthermore, cognitive impairment associated with synaptic loss in the NBM may be mediated by its pathological impact on NBM white matter tracts.

Purpose

Prostate-specific membrane antigen positron emission tomography (PSMA-PET) guided targeted biopsy has shown potential for detecting more prostate cancer (PCa) cases. However, relying exclusively on imaging may risk missing lesions, an issue that could be addressed by incorporating radiation-guided technology. Accordingly, we aimed to develop a novel PSMA radiotracer with a long half-life, [⁶⁴Cu]Cu-DOTA-PSMA-3Q, and evaluate its targeting accuracy. Additionally, this research explored the practicability of real-time lesion verification during surgical interventions.

Methods

In this study, we synthesized the radiotracer [⁶⁴Cu]Cu-DOTA-PSMA-3Q and verified its PSMA specificity and safety. We prospectively enrolled 18 patients with suspected PCa for PET/CT imaging to assess the efficacy of PCa detection; 10 patients underwent targeted biopsy combined with standard template biopsy at an interval of 24 h after injection. The radioactivity of the biopsy tissue was quantified in counts per minute (CPM) using a gamma spectrometer intraoperatively.

Results

The efficacy and specificity of [⁶⁴Cu]Cu-DOTA-PSMA-3Q were confirmed through preclinical cell and animal studies. In clinical settings, PET/CT imaging performed 2 h after injection visualized all of the PSMA-positive lesions both within and outside the prostate. The assessment of human organ radiation exposure indicated that the kidneys received the highest absorbed dose, followed by the bladder wall, salivary glands, and liver. In 10 patients, a total of 132 biopsy cores were extracted, with 53 cores histologically confirmed as PCa. The median CPM for PCa tissues was significantly greater at 134,148 CPM compared to 18,39 CPM for normal prostate tissues (P < 0.001). Receiver operating characteristic (ROC) curve analysis yielded an AUC of 0.8837, suggesting high diagnostic accuracy. The optimal diagnostic cut-off was established at 66 CPM, achieving a sensitivity of 77.36%.

Conclusions

Radiation-guided technology using [⁶⁴Cu]Cu-DOTA-PSMA-3Q improves the reliability of PSMA-PET image-guided biopsy, enables instant confirmation of sample lesions during surgical procedures, and holds potential for achieving optimized puncture outcomes.

Trial registration

Chinese Clinical Trial Registry ChiCTR2300072655, Registered 20 June 2023.

Purpose

This study examined the impact of venlafaxine and bupropion on the detection of nigrostriatal degeneration by dopamine transporter (DAT)-SPECT.

Methods

43 patients (70.7 ± 8.6y, 44% female) with [¹²³I]FP-CIT-SPECT under venlafaxine (n = 26, 37.5-225 mg/d), bupropion (n = 16, 150 or 300 mg/d) or both (n = 1) were included retrospectively. The striatal specific [¹²³I]FP-CIT binding ratio (SBR), its left–right asymmetry and the putamen-to-caudate ratio were transformed to z-scores and submitted to a cluster analysis for data-driven categorization.

Results

Two clusters were identified. The first cluster (37% cases) showed a Parkinson’s disease (PD)-like pattern: median striatal SBR/asymmetry/putamen-to-caudate z-score -4.5/4.9/-3.8. The second cluster (63%) showed symmetric reduction with normal intra-striatal gradient: median striatal SBR/asymmetry/putamen-to-caudate z-score -2.7/0.4/0.2. Patients with follow-up clinical reference diagnoses of neurodegenerative (n = 8) and non-neurodegenerative (n = 16) parkinsonism fell exclusively into the former or the latter cluster, respectively (p < 0.001).

Conclusion

Venlafaxine and bupropion cause uniform reduction of the striatal [¹²³I]FP-CIT SBR that can be distinguished from PD-like reductions.