European Journal of Nuclear Medicine and Molecular Imaging最新文献

Objective

This study aims to conduct a bibliometric analysis to explore research trends, collaboration patterns, and emerging themes in the PET/MR field based on published literature from 2010 to 2024.

Methods

A detailed literature search was performed using the Web of Science Core Collection (WoSCC) database with keywords related to PET/MR. A total of 4,349 publications were retrieved and analyzed using various bibliometric tools, including VOSviewer and CiteSpace.

Results

The analysis revealed an initial increase in PET/MR publications, peaking at 495 in 2021, followed by a slight decline. The USA, Germany, and China were the most prolific countries, with the USA demonstrating strong collaborative networks. Key institutions included the Stanford University, Technical University of Munich and University of Duisburg-Essen. Prominent authors were primarily from Germany, with significant contributions from University Hospital Essen. Major journals in the field included the European Journal of Nuclear Medicine, Journal of Nuclear Medicine, and Physics in Medicine and Biology. Emerging research areas focused on oncology, neurological disorders, and cardiovascular diseases, with keywords such as “prostate cancer,” “Alzheimer’s disease,” and “breast cancer” showing high research activity. Recent trends also highlight the growing integration of AI, particularly deep learning, to improve imaging reconstruction and diagnostic accuracy.

Conclusion

The findings emphasize the need for continuous investment, strategic planning, and technological innovations to expand PET/MR’s clinical applications. Future research should focus on optimizing imaging techniques, fostering international collaborations, and integrating emerging technologies like artificial intelligence to enhance PET/MR’s diagnostic and therapeutic potential in precision medicine.

Purpose

A novel theranostic radiopharmaceutical targeting prostate-specific membrane antigen (PSMA), [⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu–NYM032, was developed and its diagnostic and therapeutic potential in the treatment of prostate cancer (PCa) was preliminarily evaluated.

Methods

The diagnostic efficacy of the PET tracer [⁶⁸Ga]Ga–NYM032 was first evaluated in PSMA-positive xenograft-bearing models (LNCaP models), followed by evaluation in 10 PCa patients using [⁶⁸Ga]Ga–PSMA617 a comparator. Finally, the therapeutic potential of [¹⁷⁷Lu]Lu–NYM032 was evaluated in LNCaP models.

Results

[⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu–NYM032 was well-tolerated, and no adverse events were observed in the preclinical and clinical studies. [⁶⁸Ga]Ga–NYM032 demonstrated PSMA specificity and high radioactive uptake in LNCaP tumors. [⁶⁸Ga]Ga–NYM032 uptake (SUV_max) did not differ from [⁶⁸Ga]Ga–PSMA617 uptake in the same in situ lesions at the same p.i. time point (median 9.40 vs. 6.85, P = 0.123, n = 8). Compared with [⁶⁸Ga]Ga–PSMA617 uptake, [⁶⁸Ga]Ga–NYM032 uptake was significantly higher in osseous metastases (median 5.10 vs. 3.88, P < 0.001, n = 48), and higher in lymph node metastases (median 7.81 vs. 5.46, n = 2). [¹⁷⁷Lu]Lu–NYM032 showed high aggregation in the lesions of LNCaP models and long retention times. [¹⁷⁷Lu]Lu–NYM032 could inhibit tumor progression in LNCaP models, and its therapeutic efficiency strengthened with increasing radio-dosage (18.5–74 MBq/mouse). The tumor volume in the high radio-dosage treatment group (74 MBq/mouse) was significantly smaller than that in the blank control group at 21 days p.i. (107.14 ± 13.68 mm³ vs. 1351.86 ± 249.98 mm³, P < 0.001, n = 7).

Conclusion

[⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-NYM032 has considerable potential as a novel and powerful theranostic radiopharmaceutical for PCa.

Trial registration

The clinical evaluation of this study was registered at Clinicaltrial.gov (NCT06389695) on 29 Apr, 2024.

Purpose

Prostate-specific membrane antigen (PSMA) radioligand therapy is a promising treatment for metastatic castration-resistant prostate cancer (mCRPC). Several beta or alpha particle-emitting radionuclide-conjugated small molecules have shown efficacy in late-stage mCRPC and one, [[177Lu]Lu]Lu-PSMA-617, is FDA approved. In addition to tumor upregulation, PSMA is also expressed in kidneys and salivary glands where specific uptake can cause dose-limiting xerostomia and potential for nephrotoxicity. The PSMA inhibitor 2-(phosphonomethyl)pentanedioic acid (2-PMPA) can prevent kidney uptake in mice, but also blocks tumor uptake, precluding its clinical utility. Preferential delivery of 2-PMPA to non-malignant tissues could improve the therapeutic window of PSMA radioligand therapy.

Methods

A tris(isopropoxycarbonyloxymethyl) (TrisPOC) prodrug of 2-PMPA, JHU-2545, was synthesized to enhance 2-PMPA delivery to non-malignant tissues. Mouse pharmacokinetic experiments were conducted to compare JHU-2545-mediated delivery of 2-PMPA to plasma, kidney, salivary glands, and C4-2 prostate tumor xenograft. Imaging studies were conducted in rats and mice to measure uptake of PSMA PET tracers in kidney, salivary glands, and prostate tumor xenografts with and without JHU-2545 pre-treatment.

Results

JHU-2545 resulted in approximately 3- and 53-fold greater exposure of 2-PMPA in rodent salivary glands (18.0 ± 0.97 h*nmol/g) and kidneys (359 ± 4.16 h*nmol/g) versus prostate tumor xenograft (6.79 ± 0.19 h*nmol/g). JHU-2545 also blocked rodent kidneys and salivary glands uptake of the PSMA PET tracers [68Ga]Ga-PSMA-11 and [18 F]F-DCFPyL by up to 85% with little effect on tumor.

Conclusions

JHU-2545 pre-treatment may enable greater cumulative administered doses of PSMA radioligand therapy, possibly improving safety and efficacy.

Purpose

The aim of this study was to validate simplified methods for quantifying [⁶⁸Ga]Ga-FAPI-46 uptake against full pharmacokinetic modeling.

Methods

Ten patients with pancreatobiliary cancer underwent a 90-min dynamic PET/CT scan using a long axial field of view system. Arterial blood samples were used to establish calibrated plasma-input function from both continuous arterial sampling and image-derived input function (IDIF). Lesional [⁶⁸Ga]Ga-FAPI-46 kinetics were described using conventional non-linear plasma-input tissue-compartment models. Logan plots using 30–90 min and 30–60 min post-injection (p.i), image-based target-to-whole blood ratio (TBR), mean standardized uptake values (SUVmean) normalized to body weight, lean body mass, and body surface area, at 20–30 min, 60–70 min and 80–90 min p.i were assessed.

Results

One patient was excluded due to discontinued scan acquisition and missing arterial sampling. Thirteen tumoral lesions and 11 non-tumoral lesions were included. A reversible 2-tissue-compartment model showed most preferrable fits for all types of [⁶⁸Ga]Ga-FAPI-46 positive lesions. The distribution volume (V_T) results obtained using arterial sampling plasma-input function and those using plasma-IDIF (V_{T_plasma_IDIF}) showed an excellent correlation (Spearman rank correlation coefficient (r_s) = 0.949). Logan V_T using both time intervals were highly correlated with V_{T_plasma_IDIF} (r_s ≥ 0.938). The correlation values with V_{T_plasma_IDIF} for image-based TBR and SUVmean parameters were higher at 80–90 min (r_s ≥ 0.839) and at 60–70 min (r_s ≥ 0.835) p.i than at 20–30 min p.i (r_s ≤ 0.774).

Conclusion

Image-based TBR and SUVmean at 60–70 min p.i are suitable for quantifying [⁶⁸Ga]Ga-FAPI-46 uptake.

Trial registration

EudraCT, EudraCT 2022-001867-29. Registered 02 November 2022.

Purpose

Long axial field-of-view (LAFOV) positron emission tomography/computed tomography (PET/CT) scanners enable high sensitivity and wide anatomical coverage. Therefore, they seem ideal to perform post-selective internal radiation therapy (SIRT) ⁹⁰Y scans, which are needed, to confirm that the dose is delivered to the tumors and that healthy organs are spared. However, it is unclear to what extent the use of LAFOV PET is feasible and which dosimetry approaches results in accurate measurements.

Methods

In this retrospective analysis, a total number of 32 patients was included (median age 71, IQR 14), which had hepatocellular carcinoma, cholangiocarcinoma, or liver metastases. All patients underwent SIRT, and the post-therapy scan was acquired on a single photon emission computed tomography/computed tomography (SPECT/CT) and a LAFOV Biograph Quadra PET/CT with a 20-minute acquisition time. Post-treatment dosimetry, regarding the tumor, whole-liver and lung (LMD) absorbed dose was done using an organ-wise (Simplicit90Y) and a voxel-wise approach (HERMIA Dosimetry) which used a semi-Monte Carlo algorithm. The lung shunt fraction (LSF) was also measured using the voxel-wise approach and compared to the planned.

Results

The planning, post-treatment SPECT and PET (SPECT_pre, SPECT_post, PET_post) median tumor doses based on the organ-wise dosimetry were 276.0 Gy (200.0–330.0 Gy), 232.0 Gy (158.5–303.5 Gy) and 267.5 Gy (182.5–370.8 Gy). In contrast, the median voxel-wise PET_post dose was significantly smaller than the planned SPECT_pre (152.5 Gy (94.8–223.8 Gy); p < 0.00001). Moreover, the median tumor absorbed dose at 90% (D90) of the tumor volume was significantly higher in SPECT_post compared with PET_post (123.5 Gy; 81.5–180.0 vs. 30.5 Gy; 11.3-106.3; p < 0.00001). The PET_post measured LSF was significantly lower compared to the planned SPECT_pre (0.89%; 0.4–1.3% vs. 2.3%; 1.5–3.6%; p < 0.0001). Similarly, the measured PET_post median LMD was considerably lower to the planned SPECT_pre (1.2 Gy; 0.6–2.3 vs. 2.5 Gy; 1.4–4.7; p < 0.0001).

Conclusion

LAFOV PET enabled the direct measurement of post therapy lung dose and tumor doses that correlated well with the planned treatment doses. However, current voxel-wise-based tumor dosimetry seems to be inaccurate for LAFOV PET. In addition, dose volume histogram-based metrics also significantly underestimate the delivered dose. Therefore, improved dosimetry tools are needed for reliable voxel-wise ⁹⁰Y dosimetry to leverage the sensitivity and spatial resolution of LAFOV PET scanners.

Purpose

Nanoparticles are highly efficient vectors for ferrying contrast agents across cell membranes, enabling ultra-sensitive in vivo tracking of single cells with positron emission tomography (PET). However, this approach must be fully characterized and understood before it can be reliably implemented for routine applications.

Methods

We developed a Langmuir adsorption model that accurately describes the process of labeling mesoporous silica nanoparticles (MSNP) with ⁶⁸Ga. We compared the binding efficiency of three different nanoparticle systems by fitting the model to experimental data. We then chose the MSNP with the highest affinity for ⁶⁸Ga to study uptake and efflux kinetics in cancer cells. After intracardiac injection of 50–100 cells in mice, PET imaging was performed to test the effectiveness of cellular radiolabeling.

Results

We found that highly porous mesoporous nanoparticles (d = 100 nm) with MCM-41 pore structures can achieve radiolabeling efficiency > 30 GBq/mg using ⁶⁸Ga, without the need for any chelator. These ⁶⁸Ga conjugated particles showed strong serum stability in vitro. In mice, the ⁶⁸Ga-MSNPs predominantly accumulated in the liver with a high signal-to-background ratio and no bladder signal, indicating excellent stability of the labeled nanoparticles in vivo. Additionally, these MSNPs were efficiently taken up by B16F10 and MDA-MB-231 cancer cells, as confirmed by confocal imaging, flow cytometry analysis, and gamma counting. Finally, cardiac injection of < 100 ⁶⁸Ga-MSNP-labeled cells allowed PET/CT tracking of these cells in various organs in mice.

Conclusion

We characterized the critical parameters of MSNP-mediated direct cellular radiolabeling to improve the use of these nanoparticles as cellular labels for highly sensitive preclinical PET imaging.

Purpose

Fluorine-18 prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (¹⁸F-PSMA-1007 PET/CT) has been shown to be superior to multiparametric magnetic resonance imaging (MRI) for the locoregional staging of intermediate-risk and high-risk prostate tumors. This study aims to evaluate whether it is also superior in estimating tumor parameters, such as three-dimensional spatial localization and volume.

Methods

134 participants underwent ¹⁸F-PSMA-1007 PET/CT and MRI prior to radical prostatectomy as part of the validating paired-cohort Next Generation Trial (NCT05141760). MRI, ¹⁸F-PSMA-1007 PET/CT, and final pathology were independently assessed by blinded radiologists, nuclear medicine physicians, and pathologists, respectively. Individual tumor nodules were measured in three dimensions and cognitively registered to 38 segment prostate diagrams as per PI-RADSv2.1. Correct spatial localization was compared using McNemar test and estimation of tumor volumes were compared using linear regression and partial F-test.

Results

286 tumor nodules were identified by final histopathology. ¹⁸F-PSMA-1007 PET/CT was superior to MRI for correct localization (186 [65.0%] vs 134 [46.9%], p < 0.001) and tumor volume estimation (R² = 0.545 vs 0.431, p < 0.001). Larger tumors and higher Gleason Grade Group (GGG) were associated with correct localization by ¹⁸F-PSMA-1007 PET/CT (OR = 2.05, p < 0.001 for tumor volume and OR = 4.92, p < 0.01 for ≥ GGG3) and MRI (OR = 1.81, p < 0.001 for tumor volume and OR = 11.67, p < 0.001 for ≥ GGG3).

Conclusion

¹⁸F-PSMA-1007 PET/CT outperforms MRI for determination of three-dimensional spatial localization and volume of prostate tumors. These findings support the use of ¹⁸F-PSMA-1007 PET/CT prior to definitive treatment of localized prostate cancers.