European Journal of Nuclear Medicine and Molecular Imaging最新文献

Purpose

Enhancing therapeutic effectiveness is crucial for translating anticancer nanomedicines from laboratory to clinical settings. In this study, we have developed radioactive rhenium oxide nanoparticles encapsulated in human serum albumin ([¹⁸⁸Re]ReO_x-HSA NPs) for concurrent radiotherapy (RT) and photothermal therapy (PTT), aiming to optimize treatment outcomes.

Methods

[¹⁸⁸Re]ReO_x-HSA NPs were synthesized by a controlled reduction of ¹⁸⁸ReO₄⁻ in HSA medium and extensively characterized. The anticancer effect of [¹⁸⁸Re]ReO_x-HSA NPs was demonstrated in vitro in murine melanoma (B16F10) cell line. In vivo SPECT/CT imaging, autoradiography and biodistribution studies were performed after intratumoral injection of [¹⁸⁸Re]ReO_x-HSA NPs in melanoma tumor-bearing C57BL/6 mice. The potential of [¹⁸⁸Re]ReO_x-HSA NPs for combined RT and PTT treatment was also demonstrated in the aforesaid mice model.

Results

[¹⁸⁸Re]ReO_x-HSA NPs (size 4–6 nm) were synthesized with high colloidal and radiochemical stability. Upon laser (808 nm) exposure on B16F10 cells incubated with [¹⁸⁸Re]ReO_x-HSA NPs, only < 20% of cells were alive demonstrating high therapeutic efficacy under in vitro settings. Uniform dose distribution and retention of the radiolabeled NPs in the tumor volume were observed via SPECT/CT imaging and autoradiography studies. Tumor growth in mice model was significantly arrested with ~ 1.85 MBq dose of [¹⁸⁸Re]ReO_x-HSA NPs and simultaneous laser irradiation, demonstrating synergistic benefit of RT and PTT.

Conclusions

These results demonstrate that intrinsically radiolabeled [¹⁸⁸Re]ReO_x-HSA NPs having unique features such as high photothermal effects and favorable nuclear decay characteristics for combined RT/PTT, hold great promise for clinical translation.

Graphical Abstract

Purpose

This study aimed to identify if a subset of men can safely avoid or delay prostate biopsy based on negative results of prostate-specific membrane antigen positron emission tomography (PSMA-PET).

Materials and Methods

Among 341 consecutive cases in a prospective biopsy cohort (NCT05073653), 111 treatment-naïve men with negative PSMA-PET (PRIMARY-score 1/2) were included. All participants underwent PSMA-PET and histopathological examinations. Clinically significant prostate cancer (csPCa) was defined as Grade Group ≥ 2. Multivariate logistic regression was employed to identify predictors of non-csPCa. Receiver operating characteristic (ROC) analysis was performed to detect non-csPCa on prostate pathology. PSMA-postive patients were additionally reviewed to assess the imaging and pathological outcomes.

Results

Younger age was identified as an independent predictor (P = 0.006) for the absence of csPCa. ROC analysis of csPCa revealed the largest areas under the curve of 0.77 (0.67–0.87) and 0.78 (0.68–0.88) for individual age in the entire PSMA-negative cohort and the MRI subset, respectively (both P < 0.001). The negative predictive value (NPV) of PSMA-PET for csPCa detection improved with a decreasing age, from 88% in all, to 98% in men aged under 65 yrs (98% vs. 88%, P = 0.021), and to 100% in men aged under 60 yrs (100% vs. 88%, P = 0.040). The NPV of PSMA-PET improved from 88 to 94% when combined with negative MRI, and to 100% in men with negative MRI and aged under 65 yrs. The prevalence was 57% for csPCa and 65% for PCa of any grade.

Conclusion

We preliminarily propose that omission or postponement of prostate biopsy should be considered for men under the age of 65 yrs with negative PSMA-PET scored as PRIMARY 1 or 2. Conversely, prostate biopsy might be considered in biopsy-naïve men aged 65 yrs or older with strong clinical suspicion of PCa, despite negative PSMA-PET. Further prospective and external evaluation is needed to prove the robustness of this novel strategy.

Purpose

Basal Cell Carcinoma (BCC), the most common subtype of non-melanoma skin cancers (NMSC), is prevalent worldwide and poses significant challenges due to their increasing incidence and complex treatment considerations. Existing clinical approaches, such as Mohs micrographic surgery, are time-consuming and labour-intensive, requiring meticulous layer-by-layer excision and examination, which can significantly extend the duration of the procedure. Current optical imaging solutions also lack the necessary spatial resolution, penetration depth, and contrast for effective clinical use.

Methods

Here, we introduce photoacoustic imaging, also known as optoacoustic imaging, based Multispectral Optoacoustic Tomography (MSOT) as a promising solution for non-invasive, high-resolution imaging in dermatology, which also measures hemodynamic changes. MSOT offers high isotropic resolution (80 μm), increased tissue penetration, and contrast-enhanced 3D spatial imaging map. For the first time, we integrated an automated level set image segmentation methodology on optoacoustic images to further enhance the precision in delineating tumor boundaries. Through this proof-of-concept study in 30 subjects, we demonstrate that this segmentation allows for precise measurement of tumor width, depth, and volume, aiding in preoperative tumor mapping and surgical planning.

Results

The MSOT measurements, validated against histology, achieved a correlation coefficient of 0.84 and 0.81 for width and depth respectively, ensuring reliable tumor metrics with a low margin of error.

Conclusion

Clinicians can use these tumor metrics to optimize treatment efficacy, while preserving healthy tissue and cosmetic outcomes. This advancement has the potential to revolutionize diagnostics and treatment, significantly improving the patient outcomes in managing NMSC.

Purpose

As dual-phase amyloid-PET can evaluate amyloid (A) and neurodegeneration (N) with a single tracer injection, dual-phase tau-PET might be able to provide both tau (T) and N. Our study aims to assess the association of early-phase tau-PET scans and ¹⁸F-fluorodeoxyglucose (FDG) PET and their comparability in discriminating Alzheimer’s disease (AD) patients and differentiating neurodegenerative patterns.

Methods

58 subjects evaluated at the Geneva Memory Center underwent dual-phase ¹⁸F-Flortaucipir-PET with early-phase acquisition (eTAU) and ¹⁸F-FDG-PET within 1 year. A subsample of 36 participants also underwent dual-phase amyloid-PET (eAMY). Standardized uptake value ratios (SUVRs) were calculated to assess the correlation of eTAU and their respective ¹⁸F-FDG-PET and eAMY scans. Hypometabolism and hypoperfusion maps and their spatial overlap were also evaluated at the individual level visually and semiquantitatively. Receiver operating characteristic analyses were performed to compare the discriminative power of eTAU, FDG, and eAMY SUVR between A-/T- and A+/T + participants.

Results

Strong positive correlations were found between eTAU and FDG SUVRs (r = 0.84, p < 0.001) and eTAU and eAMY SUVRs (r > 0.87, p < 0.001). Clusters of significant hypoperfusion with good correspondence to hypometabolism topographies were found at the individual level, independently of the underlying neurodegenerative patterns. Both eTAU and FDG SUVRs significantly distinguished A+/T + from A-/T- individuals (AUC_eTAU=0.604, AUC_FDG=0.748) with FDG performing better than eTAU (p = 0.04). eAMY and eTAU SUVR showed comparable discriminative power.

Conclusion

Early-phase ¹⁸F-Flortaucipir-PET can provide perfusion information closely related to brain regional glucose metabolism and perfusion measured by early-phase amyloid-PET, even if less accurate than FDG-PET as a biomarker for neurodegeneration.

Purpose

This retrospective analysis evaluates baseline ¹⁸F-flotufolastat positron emission tomography (PET) parameters as prognostic parameters for treatment response and outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment with [¹⁷⁷Lu]Lu-PSMA-I&T.

Methods

A total of 188 mCRPC patients with baseline ¹⁸F-flotufolastat PET scans were included. Tumor lesions were semiautomatically delineated, with imaging parameters including volume-based and standardized uptake value (SUV)-based metrics. Outcome measures included prostate-specific antigen (PSA) response, PSA-progression-free survival (PSA-PFS), and overall survival (OS). Univariate and multivariate regression analyses assessed the impact of baseline imaging and pretherapeutic clinical parameters on outcome. Event time distributions were estimated with the Kaplan-Meier method, and groups were compared with log-rank tests.

Results

Significant prognostic parameters for PSA response and PSA-PFS included log-transformed whole-body SUVmax (odds ratio (OR), 3.26, 95% confidence interval (CI), 2.01–5.55 and hazard ratio (HR), 0.51, 95% CI, 0.4–0.66; both p < 0.001) and prior chemotherapy (OR 0.3, 95% CI, 0.12–0.72 and HR 1.64, 95% CI, 1.07–2.58; p = 0.008 and p = 0.028, respectively). For OS, significant prognosticators were the following log-transformed parameters: number of lesions (HR 1.38, 95% CI, 1.24–1.53; p < 0.001), TTV (HR 1.27, 95% CI, 1.18–1.37; p < 0.001), and ITLV (HR 1.24, 95% CI, 1.16–1.33; p < 0.001), with log-transformed TTV (HR 1.15, 95% CI, 1.04–1.27; p = 0.008) remaining significant in multivariate analysis.

Conclusion

At baseline, SUV-based ¹⁸F-flotufolastat PET metrics (e.g., whole-body SUVmax) serve as significant positive prognosticators for short-term outcomes (PSA response and PSA-PFS). In contrast, volume-based metrics (e.g., TTV) are significant negative prognosticators for long-term outcome (OS), in mCRPC patients treated with [¹⁷⁷Lu]Lu-PSMA-I&T.

Purpose

The potential of Large Language Models (LLMs) in enhancing a variety of natural language tasks in clinical fields includes medical imaging reporting. This pilot study examines the efficacy of a retrieval-augmented generation (RAG) LLM system considering zero-shot learning capability of LLMs, integrated with a comprehensive database of PET reading reports, in improving reference to prior reports and decision making.

Methods

We developed a custom LLM framework with retrieval capabilities, leveraging a database of over 10 years of PET imaging reports from a single center. The system uses vector space embedding to facilitate similarity-based retrieval. Queries prompt the system to generate context-based answers and identify similar cases or differential diagnoses. From routine clinical PET readings, experienced nuclear medicine physicians evaluated the performance of system in terms of the relevance of queried similar cases and the appropriateness score of suggested potential diagnoses.

Results

The system efficiently organized embedded vectors from PET reports, showing that imaging reports were accurately clustered within the embedded vector space according to the diagnosis or PET study type. Based on this system, a proof-of-concept chatbot was developed and showed the framework’s potential in referencing reports of previous similar cases and identifying exemplary cases for various purposes. From routine clinical PET readings, 84.1% of the cases retrieved relevant similar cases, as agreed upon by all three readers. Using the RAG system, the appropriateness score of the suggested potential diagnoses was significantly better than that of the LLM without RAG. Additionally, it demonstrated the capability to offer differential diagnoses, leveraging the vast database to enhance the completeness and precision of generated reports.

Conclusion

The integration of RAG LLM with a large database of PET imaging reports suggests the potential to support clinical practice of nuclear medicine imaging reading by various tasks of AI including finding similar cases and deriving potential diagnoses from them. This study underscores the potential of advanced AI tools in transforming medical imaging reporting practices.

Purpose

Cancer-associated fibroblasts (CAFs) are the primary stromal component of the tumor microenvironment in hepatocellular carcinoma (HCC), affecting tumor progression and post-resection recurrence. Fibroblast activation protein (FAP) is a key biomarker of CAFs. However, there is limited evidence on using FAP as a target in near-infrared (NIR) fluorescence imaging for HCC. Thus, this study aims to develop a novel NIR fluorescent imaging strategy targeting FAP⁺ CAFs in HCC.

Methods

The ICG-FAP-TATA probe was synthesized by conjugating a novel cyclization anti-FAP peptide with an indocyanine green derivative (ICG-NH₂) as fluorophore, capable for NIR window I (NIR-I, 700–900 nm) and II (NIR-II, 1000–1700 nm) imaging. Its efficacy in lesion localization and other potential applications was evaluated.

Results

In vivo imaging of subcutaneous HCC models revealed that ICG-FAP-TATA specifically targeted FAP⁺ CAFs in the stroma and detected differences in CAFs loading within lesions. The fluorescence intensity/tumor-to-background ratio (TBR) positively correlated with FAP expression (R² > 0.8, p < 0.05). Ex vivo incubation of tumor tissues with ICG-FAP-TATA provided stable fluorescence imaging of tumors in subcutaneous and orthotopic HCC models, including different cell line co-culture systems (LM3-luc, MHCC97H-luc, HepG2-luc + LX2), and various liver backgrounds (healthy/fibrotic) (n = 5 per group). TBR of the tumor mice models was higher for NIR-II than NIR-I imaging (3.89 ± 1.27 vs. 2.64 ± 0.64, p < 0.05). Moreover, NIR-I/II imaging of fresh tissues from seven patients with HCC undergoing surgery incubated with ICG-FAP-TATA visually provided the spatial distribution heterogeneity of CAFs. The targeted fluorescence was relatively enriched more in the blood flow direction and at the tumor edge, both of which were associated with tumor metastasis (all p < 0.05).

Conclusion

This study presents a rapid and effective method for detecting HCC lesions, locating FAP⁺ CAFs, and visualizing high-risk areas for tumor metastasis at the macroscopic level. It offers a new promising approach with translational potential for imaging HCC.