EJNMMI Research最新文献

Background: The number of [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG)-PET/CT scans performed has significantly increased in the last decade in line with the increasing trend of oncological malignancies. Such images, which signal high glucose-uptake areas are key in defining the extent of the disease, staging and response to therapy. Processing and evaluation of ([¹⁸F]FDG)-PET/CT scans, however, require manual annotation by well-trained specialists and above all time. In time and resource-constrained settings meeting the increasing demand for PET/CT scans has become challenging. The main goal of our study was to test the relationship between the volumes predicted by the deep learning algorithm and the manually segmented ones. The secondary objective goal was to measure the extent at which the predictive accuracy is associated with normal background uptake.

Results: The study sample included 1334 [¹⁸F]FDG-PET/CT scans from subjects with histologically confirmed diagnoses of lung cancer, lymphoma, and melanoma. 933 (70%) [¹⁸F]FDG-PET/CT scans were used as the training dataset and 267 (20%) scans were used as an internal validation dataset. A subsample of 134 (10%) [¹⁸F]FDG-PET/CT scans not used for training was used as the test dataset. The segmentation model was implemented with the nnU-Net convolutional network available in the MONAI framework. Model performance was measured with the Dice score. Correlation between manual and predicted segmentation was assessed using linear correlation. Totalsegmentator tool was used to identify lesions location and assess the tumor-to-background ratio (TBR) for quantitative analysis. Network achieved Dice scores of 0.918 (validation) and 0.879 (test), showing strong agreement with manual segmentations. The model achieved an F1 score of 0.91 on the test set. High correlation (R=0.82, p<0.0001) was observed between predicted and ground truth volumes. Segmentation accuracy improved with higher TBRs, as lesions with TBR>2 had significantly better Dice scores than those with lower contrast (TBR ≤ 1-2 or≤1).

Conclusions: These results are consistent with previous reports on PET-based segmentation, further validating nnU-Net as a reliable approach for detecting hypermetabolic lesions and assessing global disease burden in FDG-PET imaging. Moreover, the significant relationship between TBR and segmentation accuracy suggests the possibility of further improvements by integrating metabolic profile into the predictive model.

Background: Myocardial flow reserve (MFR), derived from dynamic single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), offers quantitative insight into coronary physiology and may overcome limitations of conventional semi-quantitative SPECT. We aimed to systematically review and meta-analyse the diagnostic accuracy and prognostic value of SPECT-derived MFR in comparison with invasive coronary angiography (ICA), PET-MPI, and long-term patient outcomes.

Results: A comprehensive literature search was done in scientific databases for studies comparing SPECT-derived MFR in patients with known or suspected coronary artery disease to ICA, PET-MPI, or ≥ 12-month follow-up for major adverse cardiac events. A meta-analysis was conducted using random-effects models for studies comparing SPECT-MFR with PET-MPI, and reporting diagnostic performance metrics including sensitivity and specificity. Thirty-two studies were included (n = 19 for ICA; n = 8 for PET-MPI; 1 for both ICA and PET-MPI and n = 4 for follow-up). Thirty studies showed a significant correlation between SPECT-derived MFR and reference standards with excellent area under the curve values (AUC > 0.7) reported. Six PET-MPI comparator studies (with a total number of participants, n = 180) were included in the meta-analysis, yielding a pooled sensitivity of 78.5% (95% CI: 71.7-84.1%) and specificity of 89.3% (95% CI: 70.4-96.7%) (diagnostic odds ratio = 15.7 (95% CI: 6.270-39.269)). MFR consistently predicted major adverse cardiac events in prognostic studies, independent of obstructive coronary status.

Conclusions: Quantitative MFR derived from dynamic SPECT-MPI correlates well with established diagnostic reference tests and independently predicts adverse outcomes. While PET remains the reference standard, SPECT-MPI offers a viable and more accessible alternative. Standardised protocols and large-scale prospective validation are needed to optimise its clinical implementation.

Prospero registration: CRD42024507703.

Background: Neuromelanin is mostly located in dopaminergic neurons in the substantia nigra (SN) pars compacta, and can be detected by magnetic resonance imaging (MRI). It is a promising imaging-base biomarker for neurological diseases. We previously developed a melanin-specific probe N-(2-(diethylamino)-ethyl)-¹⁸F-5-fluoropicolinamide (¹⁸F-P3BZA), which was initially developed for the imaging of melanoma. ¹⁸F-P3BZA exhibited high levels of binding to the melanin in vitro and in vivo with high retention and favorable pharmacokinetics. In this study we further investigated whether ¹⁸F-P3BZA could be used to quantitatively detect neuromelanin in the SN in healthy rhesus macaques.

Results: ¹⁸F-P3BZA exhibited desired hydrophobicity with estimated log K ow 5.08 and log D7.4 1.68. ¹⁸F-P3BZA readily crossed the blood-brain barrier with brain transport coefficients (Kin) of 40 ± 8 µL g-1s-1. ¹⁸F-P3BZA accumulated specifically in neuromelanotic PC12 cells, melanin-rich melanoma cells, and melanoma xenografts. ¹⁸F-P3BZA binding was significantly higher in B16F10 cells vs. amelanotic SKOV3 cells (6.17 ± 0.53%IA vs. 0.24 ± 0.05%IA) and in pigmented PC12 cells vs. non-pigmented PC12 cells(7.09 ± 0.15%IA and 0.29 ± 0.05%IA).In the biodistribution study, ¹⁸F-P3BZA had higher accumulation in B16F10 tumors (6.31 ± 0.99%IA/g) than in SKOV3 tumors (0.25 ± 0.09%IA/g). Meanwhile, ¹⁸F-P3BZA uptake in B16F10 tumors could be blocked by excess cold ¹⁹F-P3BZA (0.81 ± 0.02%IA/g, 88% inhibition, p < 0.05). PET/MRI ¹⁸F-P3BZA provided clear visualization of neuromelanin-rich SN at 30-60 min after injection in healthy macaques. The SN to cerebella ratios were 2.7 and 2.4 times higher at 30 and 60 min after injection. In vitro autoradiography studies ¹⁸F-P3BZA exhibited high levels of binding to the SN of healthy human and almost no binding to the SN of Parkinson's disease patient.

Conclusion: ¹⁸F-P3BZA PET/MRI clearly images neuromelanin in the SN, and may assist in the early diagnosis of neurological diseases associated with abnormal neuromelanin expression.

Background: Peptide receptor radionuclide therapy (PRRT) employing [¹⁷⁷Lu]Lu-[DOTA-Tyr³]octreotate has been established as treatment for patients with metastatic neuroendocrine tumors (NETs) that overexpress the somatostatin receptor (SSTR). While PRRT improves survival and quality of life, curative responses remain rare. One way to enhance PRRT efficacy is to combine it with radiosensitizing agents such as heat shock protein 90 (HSP90) inhibitors. HSP90 is a highly conserved molecular chaperone essential for the maturation and stabilization of over a hundred proteins, including proteins involved in the DNA damage response and oncogenic signaling. HSP90-inhibition has been shown to potentiate PRRT, however the mechanism behind this radiosensitizing effect remains unknown. This study aimed to elucidate mechanisms involved in the radiosensitizing effect of HSP90 inhibition.

Results: The radiosensitizing effect of HSP90 inhibitor ganetespib in the context of PRRT and external beam radiotherapy (EBRT) was tested using viability assays for NET cell models GOT1 and BON1-SSTR2. Ganetespib significantly enhanced radiation-induced cytotoxicity in both models. To explore underlying mechanisms, we assessed DNA double-strand break (DSB) repair by quantifying 53BP1 foci numbers, and functionally evaluated DSB repair pathways by RAD51 foci quantification and end-joining assay. Although HSP90 inhibition reduced RAD51 foci numbers, its effect on non-homologous end joining and overall DSB persistence was limited. Finally, potential DSB repair-independent mechanisms of radiosensitization were assessed for GOT1 cells using RNA sequencing. Transcriptomic analysis revealed enrichment of pathways related to loss of HSP90 function, such as protein folding and response to heat stress, following combination treatment. This was consistent with effects observed after HSP90 inhibitor monotherapy.

Conclusions: Given the lack of significant effects on direct DNA repair or transcriptomic responses, our findings suggest that HSP90 inhibition radiosensitizes NET cells by inducing a pleiotropic effect on multiple stress-related pathways at the protein level, rather than solely through disruption of DNA damage response mechanisms. This effect is likely driven by loss of HSP90 function and subsequent cumulated unfolded protein and proteotoxic stress.

Background: Oxytocin is a neuropeptide with therapeutic potential for several neuropsychiatric and pain-related disorders. Intranasal delivery is proposed to enable access to the central nervous system via the trigeminal nerve and olfactory nerves, thereby bypassing the blood-brain barrier. However, direct evidence of biodistribution following intranasal administration in humans is limited. This study evaluated the feasibility of imaging oxytocin uptake using a novel PET tracer, [¹³N]oxytocin, in healthy volunteers.

Results: Six participants received intranasal [¹³N]oxytocin and underwent whole-body or head PET/MRI scans. High tracer uptake was observed in the nasal cavity within the first 5 min, followed by a decline and systemic absorption. Tracer uptake in the trigeminal ganglia and brain varied between individuals, with no clear dose-dependency. One participant with rhinitis showed altered uptake and clearance patterns. Time-activity curves indicated tracer presence in brain regions 25-45 min post-administration, but image co-registration was challenged by high nasal activity and spillover effects. Radiation dosimetry analysis identified the nasal cavity as the critical organ, limiting allowable doses. Despite detectable presence in some brain regions, [¹³N]oxytocin uptake was low and variable.

Conclusions: Intranasal [¹³N]oxytocin administration results in rapid and substantial nasal cavity uptake and detectable, but variable, tracer distribution to trigeminal and brain regions. While this technique offers insight into intranasal peptide delivery, limitations related to variable absorption, short half-life, and image co-registration must be addressed. Accordingly, [¹³N]oxytocin is not presently well suited for central nervous system receptor imaging via intranasal administration. Peripheral receptor imaging after intravenous administration may still be feasible, and further optimisation of tracer chemistry, administration protocols, and imaging strategies is warranted.

Trial registration: ClinicalTrials.gov identifier: NCT06955650 (registered May 5, 2025).

Background: Prostate cancer (PCa) remains one of the most commonly diagnosed malignancies and a leading cause of cancer-related morbidity and mortality among men worldwide. Despite considerable progress in diagnostic and therapeutic modalities, conventional approaches often fall short in capturing disease heterogeneity and managing advanced or treatment-resistant cases. Over the past years, molecular imaging and targeted radionuclide therapy within a theranostic framework have emerged as powerful tools to potentially overcome these limitations. In this context, copper radioisotopes-particularly copper-61 (T_1/2 = 3.33 h; 61% β⁺), copper-64 (T_1/2 = 12.7 h; 17% β⁺, 39% β^-), and copper-67 (T_1/2 = 2.58 d; 100% β^-)-have garnered considerable attention due to their favorable half-lives, straightforward coordination chemistry, and optimal physical decay properties for both imaging and therapy.

Main body: This review comprehensively examines the progress and prospects of copper-based radiopharmaceuticals for PCa theranostics, with particular emphasis on agents targeting prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR), the two most extensively studied and clinically relevant molecular targets in this setting. Alternative markers are also discussed as promising avenues to tackle disease heterogeneity and expand the clinical applicability of these conjugates. By consolidating preclinical and clinical evidence, we aim to identify current challenges and opportunities in the development of copper-based radiopharmaceuticals, and contribute to a paradigm shift toward the widespread clinical adoption of these novel radiopharmaceutical platforms for improved patient care.

Conclusion: Copper-based radiopharmaceuticals represent a promising class of agents with the potential to refine PCa management. As research advances, these compounds are poised to enhance diagnostic precision and therapeutic efficacy, paving the way for more personalized strategies and favorable clinical outcomes.

Background: Accurate diagnosis and staging are essential for optimal treatment planning of prostate cancer. By combining functional and anatomical imaging, PSMA-PET/mpMRI offers a potential to improve lesion detection and enhance staging accuracy. This study aimed to evaluate the diagnostic performance of lesion detection and local staging of prostate cancer using combined PSMA-PET/mpMRI compared to standalone mpMRI or PSMA-PET.

Results: Fifty-five patients with intermediate- to high-risk prostate cancer scheduled for robot-assisted laparoscopic radical prostatectomy were included. All patients underwent [⁶⁸Ga]PSMA-PET/mpMRI prior to surgery. Whole-mount histopathology and surgical report served as reference standard. Two radiologists independently evaluated mpMRI, while two nuclear medicine physicians assessed PSMA-PET. For the PSMA-PET/mpMRI analysis, a consensus evaluation was performed by a new set of readers in two teams, each comprising one radiologist and one nuclear medicine physician. Lesion localization was reported based on the PI-RADS v2.1 sector map and compared to histopathology. Among 130 histopathologically confirmed lesions, mean detection rates were 38% (49.5/130) for PSMA-PET/mpMRI, 32% (41/130) for mpMRI and 32% (41/130) for PSMA-PET. For clinically significant prostate cancer (csPC) (≥0.5 ml, ≥ISUP 2; 42 lesions), mean detection rates were 85% (35.5/42) for PSMA-PET/mpMRI, 75% (31.5/42) for mpMRI and 70% (29.5/42) for PSMA-PET. The mean false discovery rates were 8% (PSMA-PET/mpMRI), 15% (mpMRI) and 12% (PSMA-PET). The likelihood of extraprostatic extension (EPE) and seminal vesicle invasion (SVI) were scored using a 5-point Likert scale, where scores of 1-3 were classified as negative and scores of 4-5 were considered positive. Sensitivity for EPE was 32% for PSMA-PET/mpMRI, 37% for mpMRI and 7% for PSMA-PET, with a specificity of 100%, 96% and 98%, respectively. For SVI, sensitivity was 50% for PSMA-PET/mpMRI and 38% for mpMRI and PSMA-PET, with a specificity of 100%, 95% and 97% respectively.

Conclusions: PSMA-PET/mpMRI provided higher and a more consistent performance in localized prostate cancer detection and staging without increasing false-positive findings.

Background: The hypoxic status of cancer tumour is disparate within tumour microenvironment and is considered as the main cause of treatment resistance. Chondrosarcoma, a type of bone cancer, combines heterogonous tumour microenvironment and resistance to therapies. We aimed to image tumour microenvironment response to hypoxia activated prodrug therapy with Evofosfamide (TH-302) on a rat chondrosarcoma model thanks to an original multimodal imaging strategy. Bimodal imaging strategy consisted of nuclear imaging and MRI on TH-302 treated and control animals. To monitor TH-302 effects on tumour growth and structure, we measured T2 and ADC by MRI and we used ¹⁸F-FDG to explore tumour metabolism. ¹⁸F-FMISO and APT to Guanidyl ratio CEST MRI evaluated hypoxic status. Proteoglycans in the extracellular matrix were explored in vivo by a radiotracer targeting proteoglycans (^99mTc-NTP 15 - 5) and GAG CEST MRI. Immunohistochemistry, biochemical assays and RNA sequencing were performed to confirm in vivo observations.

Results: TH-302 demonstrated a strong efficacy on tumour structure with a reduction of its volume of 75% at the end of the protocol, a modification of the tumour microstructures and a decreased of both cellularity and cell proliferation. The drug also modified the tumour metabolisms as shown by ¹⁸F-FDG PET and GLUT-1 staining for the energetic one, CEST-MRI and pimonidazole for the hypoxic status and ^99mTc-NTP 15 - 5 SPECT and sGAG assay for proteoglycans. Genomic analysis shown changes in gene expression related to therapy.

Conclusions: TH-302 shows an in vivo anti-tumour activity in chondrosarcoma. Our multimodal imaging approach allows monitoring complex exchanges between tumour cells and their neighboring under therapy.