European Journal of Nuclear Medicine and Molecular Imaging最新文献

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: The identification of tau accumulation within living brains holds significant potential in facilitating accurate diagnosis of progressive supranuclear palsy (PSP). While visual assessment is frequently employed, standardized methods for tau positron emission tomography (PET) specifically in PSP are absent. We aimed to develop a visual reading algorithm dedicated to the evaluation of [¹⁸F]Florzolotau PET in PSP.

Methods: 148 PSP and 30 healthy volunteers were divided into a development set (for the establishment of the reading rules; n = 89) and a testing set (for the validation of the reading rules; n = 89). For differential diagnosis, 55 α-synucleinopathies were additionally included into the testing set. The visual reading method was established by an experienced assessor (Reader 0) and was then validated by Reader 0 and two additional readers on regional and overall binary manners. A positive binding in both midbrain and globus pallidus/putamen regions was characterized as a PSP-like pattern, whereas any other pattern was classified as non-PSP-like.

Results: Reader 1 (94.4%) and Reader 2 (93.8%) showed excellent agreement for the overall binary determination against Reader 0. The regional binary determinations of midbrain and globus pallidus/putamen showed excellent agreement among readers (kappa > 0.80). The overall binary evaluation demonstrated reproducibility of 86.1%, 94.4% and 77.8% for three readers. The visual reading algorithm showed high agreement with regional standardized uptake value ratios and clinical diagnoses.

Conclusion: Through the application of the suggested visual reading algorithm, [¹⁸F]Florzorotau PET imaging demonstrated a robust performance for the imaging diagnosis of PSP.

Objective: This study aimed to investigate [¹⁸F]fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG PET) mapping for cerebral glucose metabolism in drug-sensitive and drug-resistant pediatric epilepsy patients.

Methods: This retrospective study enrolled 40 patients and 25 controls. Patients were categorized into drug-sensitive epilepsy (n = 22) and drug-resistant epilepsy (n = 18) according to the seizure frequency at follow-up. All patients underwent two [¹⁸F]FDG PET scans separated by a minimum of one year. Absolute asymmetry index (|AI|) was calculated for assessing metabolic differences and changes in epileptic foci. Statistical Parametric Mapping (SPM) was utilized to reveal voxel-wise metabolic characteristics and alterations throughout the brain. Network analysis based on graph theory was used to investigate network-level differences between the two patient groups.

Results: The drug-sensitive group showed a lower |AI| at both baseline (P = 0.038) and follow-up (P = 0.003) PET scans than the drug-resistant group. |AI| decreased in the drug-sensitive group and increased in the drug-resistant group across scans, but these trends were not statistically significant (P = 0.240 and P = 0.450, respectively). Both groups exhibited hypometabolism at baseline. The drug-sensitive group showed less hypometabolic brain regions than the drug-resistant group. The drug-sensitive maintained stable level of hypometabolism between the two scans, whereas the drug-resistant group showed an increasing hypometabolism. Network analysis demonstrated that the drug-sensitive group had a higher global efficiency, average degree, and clustering, along with a shorter characteristic path length compared to the drug-resistant group.

Conclusions: For the first time, this study revealed in vivo cerebral glucose metabolic pattern of nonsurgical pediatric epilepsy patients treated by antiepileptic drugs. Especially, drug-resistant epilepsy patients represented significantly extensive and progressive hypometabolism with inefficient brain network connectivity compared with drug-sensitive epilepsy. [¹⁸F]FDG PET imaging may be a potential visual approach for theranostics of epilepsy patients.

Purpose: This study aimed to evaluate the association between pretreatment [18F]FDG PET/CT-derived biomarkers and outcomes in metastatic breast cancer (mBC) patients treated with antibody-drug conjugates (ADCs) Sacituzumab Govitecan (SG) and Trastuzumab Deruxtecan (T-DXd).

Methods: A retrospective bicentric analysis was conducted on triple-negative mBC (mTNBC) patients treated with SG and HER2-low mBC patients treated with T-DXd, who underwent [18F]FDG PET/CT scans before therapy. Key biomarkers, including maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV) and maximum tumor dissemination (Dmax), were measured. Their prognostic value for progression-free survival (PFS) and overall survival (OS) was assessed using Cox models and Kaplan-Meier curves.

Results: 128 patients were included: 71 mTNBC treated with SG and 57 HR-positive and -negative HER2-low mBC treated with T-DXd. Median follow-up was 12.9 months. In the SG cohort, median PFS and OS were 4.8 and 8.9 months, respectively. High Dmax (HR 2.1, 95% CI 1.1-4.3) and high TMTV (HR 2.9, 95% CI 1.2-6.6) were independently associated with shorter OS. In the T-DXd cohort, median PFS and OS were 5.8 and 9.0 months, respectively. High Dmax (HR 2.1, 95% CI 1.2-3.9) and high TMTV (HR 2.4, 95% CI 1.0-6.5) independently correlated with shorter PFS and shorter OS, respectively.

Conclusion: Pretreatment [18F]FDG PET/CT-derived biomarkers, namely TMTV and Dmax, have significant prognostic value in patients with mTNBC and HER2-low mBC treated with SG and T-DXd. These biomarkers improve prognostic prediction and may optimize treatment strategies, warranting their clinical use, but larger studies are needed to validate these findings.

The introduction of dual-energy X-ray absorptiometry (DXA) technology in the 1980s revolutionized the diagnosis, management and monitoring of osteoporosis, providing a clinical tool which is now available worldwide. However, DXA measurements are influenced by many technical factors, including the quality control procedures for the instrument, positioning of the patient, and approach to analysis. Reporting of DXA results may be confounded by factors such as selection of reference ranges for T-scores and Z-scores, as well as inadequate knowledge of current standards for interpretation. These points are addressed at length in many international guidelines but are not always easily assimilated by practising clinicians and technicians. Our aim in this report is to identify key elements pertaining to the use of DXA in clinical practice, considering both technical and clinical aspects. Here, we discuss technical aspects of DXA procedures, approaches to interpretation and integration into clinical practice, and the use of non-bone mineral density measurements, such as a vertebral fracture assessment, in clinical risk assessment.