European Journal of Nuclear Medicine and Molecular Imaging最新文献

Objectives

This study aimed to evaluate the predictive value of [¹⁸F]AlF-NOTA-FAPI-04 PET/CT for pathological response to neoadjuvant chemotherapy (NCT) and prognosis in patients with locally advanced pancreatic ductal adenocarcinoma (LAPDAC).

Methods

This study included 34 patients with histopathologically and radiologically confirmed LAPDAC who received [¹⁸F]AlF-NOTA-FAPI-04 PET/CT scans before NCT. After 4–6 cycles of NCT, these patients underwent radical resection. Pathological response to NCT was assessed by pathological tumor regression grades (TRG) based on the Evans system. PET/CT parameters were evaluated for their association with TRG, recurrence-free survival (RFS) and overall survival (OS) after NCT, including the maximum standardized uptake value (SUV_max), FAPI-avid tumor volume (FTV), total lesion FAP expression (TLF) of primary tumor, total FAPI-avid pancreatic volume (FPV) and total pancreatic FAP expression (TPF) of total pancreas.

Results

Of 34 patients with LAPDAC, 14 patients had a pathologic good response (PGR, Evans III-IV), and 20 patients had a pathologic poor response (PPR, Evans I-II). Both the primary tumor SUV_max, FTV and TLF, and total pancreas FPV and TPF in the PGR groups were significantly lower than those in the PPR groups. Furthermore, SUV_max and TLF were higher in poorly differentiated LAPDAC than in well-moderately differentiated neoplasms. The FTV, TLF, FPV and TPF were closely associated with RFS and OS. On multivariate analysis, patients with FTV > 54.21 and TLF > 290.21 had a worse RFS and OS, respectively (HR = 3.24, P = 0.014 and HR = 3.35, P = 0.019) and OS (HR = 7.35, P = 0.002 and HR = 7.09, P = 0.004) in LAPDAC after NCT.

Conclusions

The parameters of [¹⁸F]AlF-NOTA-FAPI-04 PET/CT had the excellent performance for predicting pathologic TRG after NCT in LAPDAC. FTV and TLF were independent postoperative prognostic factors for RFS and OS for LAPDAC.

Purpose

Prostate-specific membrane-antigen positron emission tomography (PSMA PET) is a promising candidate for non-invasive characterization of prostate cancer (PCa). This study evaluated whether PET with tracers [⁶⁸Ga]Ga-PSMA-11 or [¹⁸F]PSMA-1007 is capable to depict intratumour heterogeneity of histological PSMA expression.

Methods

Thirty-five patients with biopsy-proven primary PCa without evidence of metastatic disease nor prior interventions were prospectively enrolled. All patients underwent PSMA PET combined with computer tomography (CT) with either [⁶⁸Ga]Ga-PSMA-11 (cohort I, 20 patients) or [¹⁸F]PSMA-1007 (cohort II, 15 patients) followed by radical prostatectomy. Specimens were scanned by ex-vivo CT and histologically prepared. On digitized whole-mount prostate sections, PCa areas with different morphologies were manually defined and H-Score of immunohistochemical PSMA expression was calculated with assistance by artificial intelligence (AI). PCa areas with similar H-Score were unified in segmentation on ex-vivo CT. After co-registration on PSMA PET-CT, Spearman’s coefficients of PSMA expression to mean and maximum standardized uptake value (SUV_mean and SUV_max) were calculated. Furthermore, the agreement of the co-registered tumour areas to gross tumour volume (GTV) in PSMA PET was analysed.

Results

Thirty-two patients were included in the final analysis. For histological PCa areas, immunohistochemical PSMA expression correlated significantly to SUV_mean and SUV_max (p < 0.001, p = 0.001). An approximate linear correlation between H-Score and SUV_mean / SUV_max was found for tumour areas larger than 400 μm² in histology (p < 0.001). Tumour areas with strong PSMA expression showed a significantly larger overlap to GTV in PSMA PET after co-registration than tumour areas with very low PSMA expression (p < 0.01). No significant differences were found between the two tracer cohorts (p = 0.72).

Conclusion

PSMA PET with both [⁶⁸Ga]Ga-PSMA-11 or [¹⁸F]PSMA-1007 is able to detect changes in histological PSMA expression within PCa lesions allowing biologically targeted radiotherapy.

Purpose

Estrogen receptor (ER) expression and heterogeneity affect endocrine therapy efficacy. ¹⁸F-fluoroestradiol (¹⁸F-FES) PET/CT is an effective non-invasive method to analyze systemic ER expression. This study aimed to examine the predictive/prognostic value of ¹⁸F-FES PET/CT for patients treated with endocrine therapy plus cyclin-dependent kinase 4/6 (CDK4/6) inhibitors.

Methods

Patients were identified from a prospective cohort for post-marketing surveillance of ¹⁸F-FES enrolled between April 2021 and April 2023 at Asan Medical Center. In this retrospective analysis, patients with ER-positive, HER2-negative recurrent/metastatic breast cancer who underwent CDK4/6 inhibitor-based endocrine therapy and pre-treatment ¹⁸F-FES PET/CT were included.

Results

A total of 127 women were included. The endocrine therapy used was aromatase inhibitors in 96 patients (76%) and fulvestrant in 31 patients (24%). There were 25 (20%) and 102 (80%) patients in the “with FES-negative” (3 completely negative, 22 mixed) and “FES-positive” groups, respectively. ¹⁸F-FES status correlated with progression-free survival (PFS) following endocrine therapy with CDK4/6 inhibitors and overall survival (OS) (“with FES-negative” group: hazard ratio for PFS, 3.9, p < 0.001; for OS, 3.7, p = 0.008). Reduced benefit from endocrine treatment in the “with FES-negative” group was consistent across subgroups including menopausal status, endocrine sensitivity, and treatment regimen.

Conclusion

ER expression determined by ¹⁸F-FES PET/CT predicted the efficacy of CDK4/6 inhibitor-based endocrine therapy and was prognostic for survival in recurrent/metastatic ER-positive, HER2-negative breast cancer.

As the smallest antibody fragment with specific binding affinity, nanobody-based nuclear medicine has demonstrated significant potential to revolutionize the field of precision medicine, supported by burgeoning preclinical investigations and accumulating clinical evidence. However, the visualization of nanobodies has also exposed their suboptimal biodistribution patterns, which has spurred collaborative efforts to refine their pharmacokinetic and pharmacodynamic profiles for improved therapeutic efficacy. In this review, we present clinical results that exemplify the benefits of nanobody-based molecular imaging in cancer diagnosis. Moreover, we emphasize the indispensable role of molecular imaging as a tool for evaluating and optimizing nanobodies, thereby expanding their therapeutic potential in cancer treatment in the foreseeable future.

Objective

Tafamidis has shown potential in slowing disease progression in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to evaluate serial changes on [^99mTc]Tc-pyrophosphate (PYP) scintigraphy during tafamidis treatment for hereditary ATTR-CM.

Methods

We retrospectively analyzed a prospectively collected cohort of Ala97Ser (A97S) hereditary ATTR-CM patients treated with tafamidis (61 mg/day) and a control group comprising A97S hereditary ATTR-CM patients who had not received disease-modifying medications. The tafamidis group was further divided into two cohorts: cohort A received [^99mTc]Tc-PYP SPECT/CT scans at baseline, 1 year, and 2 years; cohort B at baseline, 2 years, and 3 years. Visual score, planar heart to contralateral lung (H/CL) ratio, and volumetric heart to lung (H/L) ratio were measured.

Results

Nineteen patients were enrolled in the tafamidis group and nine in the control group. After 2 years of follow-up, a significant decrease in volumetric H/L ratio (3.86 ± 0.91 to 3.01 ± 0.19, p < 0.001) was noted in the tafamidis group, while there was no significant change in the control group. When evaluated over time, a significant decrease in volumetric H/L ratio was observed during the first year of tafamidis treatment (3.75 ± 0.37 to 2.82 ± 0.15, p = 0.004), followed by stable [^99mTc]Tc-PYP uptake in the subsequent two years (2.82 ± 0.15 to 2.83 ± 0.18, p = 0.934 and 3.20 ± 0.14 to 3.09 ± 0.16, p = 0.404, respectively).

Conclusion

A significant reduction in [^99mTc]Tc-PYP uptake was observed in hereditary ATTR-CM patients after tafamidis treatment, particularly within the first year. While the effect appeared to be sustained, stable [^99mTc]Tc-PYP uptake without further significant reductions was observed in the subsequent years.

Purpose

Lutetium-177 Prostate-specific membrane antigen (Lu-PSMA) radioligand therapy is EMA-approved for metastatic castration resistant prostate cancer (mCRPC) after androgen receptor pathway inhibition (ARPI) and taxan-based chemotherapy. However, its effect in taxan-naïve patients is under current investigation.

Methods

We relied on the FRAMCAP database to elaborate Lu-PSMA therapy outcomes of progression-free (PFS) and overall (OS) in taxan-naïve mCRPC patients after previous ARPI treatment. Comparison was made against current standard of care with ARPI or docetaxel, irrespective of the previous used staging modality.

Results

Of 269 patients, 11% received Lu-PSMA in first/second-line mCRPC vs. 57% ARPI vs. 33% docetaxel. Mostly no significant baseline differences between Lu-PSMA and ARPI patients were observed, while Lu-PSMA patients were significantly older, received less systematic treatments and ECOG1-2 proportions were higher, relative to docetaxel patients. In PFS (13.3 vs. 8.2 months, hazard ratio [HR]: 0.70, p = 0.16) and OS analyses (68.9 vs. 39.1 months, HR: 0.64, p = 0.2), Lu-PSMA was numerically more favorable than ARPI. In additional multivariable Cox regression models, Lu-PSMA was significant better regarding PFS and OS, relative to ARPI (both p < 0.05). Compared to docetaxel, also significant better PFS (13.3 vs. 8.1 months, HR: 0.46) and OS (68.9 vs. 27.3 months, HR: 0.34, both p < 0.01) was observed for Lu-PSMA treatment. The OS advantage was also observed after multivariable adjustment (p < 0.01).

Conclusion

This retrospective single-center study including a substantial proportion of patients with treatment preference for Lu-PSMA suggests that Lu-PSMA therapy provides significantly more favorable PFS and OS outcomes in taxan-naïve mCRPC patients after previous ARPI treatment, relative to ARPI or docetaxel treatment and may be considered as an early mCRPC treatment option.

Purpose

PSMA-PET is a reference standard examination for patients with prostate cancer, but even using recently introduced digital PET detectors image acquisition with standard field-of-view scanners is still in the range of 20 min. This may cause limited access to examination slots because of the growing demand for PSMA-PET. Ultra-fast PSMA-PET may enhance throughput but comes at the cost of poor image quality. The aim of this manuscript is to evaluate the accuracy of AI-enhanced ultra-fast PSMA-PET for staging of patients with prostate cancer.

Methods

A total number of 357 whole-body [⁶⁸Ga]Ga-PSMA-11 PET datasets were included. Patients underwent two digital PET scans, one at standard and one at ultra-fast speed (table speed: 0.6–1.2 mm/s vs. 50 mm/s). A modified pix2pixHD generative adversarial network to enhance the ultra-fast images was trained with 286 datasets and evaluated with the remaining 71 datasets. The staging accuracy of ultra-fast PSMA-PET and AI-enhanced ultra-fast PET was compared with the reference standard PET separately for miTNM regions proposed by PROMISE V2.0.

Results

The AI-network significantly improved the visual image quality and detection rate in most miTNM regions compared with the non-enhanced image data (T: 69.6% vs. 43.5%, p < 0.05; N: 46.3% vs. 27.8%, p < 0.01; M1a 64.4% vs. 47.5%, p < 0.01; M1b: 85.7% vs. 72.1%, p < 0.01). However, improvement was not significant for the M1c category (42.9 vs. 28.6%, p > 0.05). Missed lesions had a smaller SUVmax and lesion size compared with detected lesions (exemplary for N: 9.5 vs. 26.5 SUVmax; 4 vs. 10 mm). SUVmax values of lesions were significantly different in all miTNM regions between the ultra-fast and reference standard PET, but only in the T-region between the AI-enhanced and reference standard PET.

Conclusion

The AI-based image enhancement improved image quality and region detection rates by a mean of 17.9%. As the sensitivity of synthetic PET for small and low-uptake lesions was limited, a potential clinical use case could be disease monitoring in patients with high tumor volume and PSMA uptake undergoing PSMA radioligand therapy. The improvement in detection rate of distant metastases was not significant. This indicates that more training data is needed to ensure robust results also for lesions that have lower appearance frequency. Future studies on accelerated PSMA-PET seem warranted.

Purpose

Since fibroblast activation protein (FAP), one predominant biomarker of cancer associated fibroblasts (CAFs), is highly expressed in the tumor stroma of various epidermal-derived cancers, targeting FAP for tumor diagnosis and treatment has shown substantial potentials in both preclinical and clinical studies. However, in preclinical settings, tumor-bearing mice exhibit relatively low absolute FAP expression levels, leading to challenges in acquiring high-quality PET images using radiolabeled FAP ligands (FAPIs) with low molar activity, because of which a saturation effect in imaging is prone to happen. Moreover, how exactly the molar dose of FAPI administered to a mouse influences the targeted PET imaging and radiotherapy remains unclear now. Therefore, this study aims to investigate the impacts of the molar dose of the administered FAPI on FAP-targeted PET imaging and radiotherapy in mouse syngeneic tumor models.

Methods

[⁶⁸Ga]Ga-FAPI-04 with various molar doses of FAPI-04 was administered to wild-type 4T1 tumor-bearing mice, followed by static PET imaging. Sigmoidal curves were generated to analyze the correlation between the standard uptake value (SUV) and the administered molar doses of FAPI-04. Similarly, [¹⁷⁷Lu]Lu-DOTAGA.(SA.FAPi)₂ with a consistent dose of radioactivity but containing different moles of DOTAGA.(SA.FAPi)₂ were injected into 4T1 tumor-bearing mice to assess the therapeutic effect. [⁶⁸Ga]Ga-FAPI-04 was also applied to different tumor models for PET/CT imaging.

Results

A gradient blocking effect was observed with increasing FAPI molar dose in [⁶⁸Ga]Ga-FAPI-04 PET imaging and [¹⁷⁷Lu]Lu-DOTAGA.(SA.FAPi)₂ treatment, with various imaging and therapeutic outcomes. [⁶⁸Ga]Ga-FAPI-04 PET exhibit potentials to characterize murine derived FAP expression with low molar dose of administered FAPI-04 using various tumor models.

Conclusion

The molar dose of FAPI in [⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-FAPI had a substantial impact on FAP-targeted imaging and therapy in mouse syngeneic tumor models. To acquire enhanced reliability and reproducibility in preclinical situation, it is critical to carefully consider the molar dose of the radiotracer when applying radiolabeled FAP ligands to FAP-targeted imaging and radiotherapy.