European Journal of Nuclear Medicine and Molecular Imaging最新文献

Purpose

Aim of this study was to analyze the safety of prostate-specific membrane antigen radioligand therapy (PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC) with preexisting moderate to severe thrombocytopenia (CTCAE ≥ 2).

Materials and methods

Seventeen mCRPC patients with preexisting thrombocytopenia (platelet count < 75 × 10⁹/L) were included in this study. Patients received a median of 3 cycles of [¹⁷⁷Lu]Lu-PSMA-617 (range 1–6). The course of platelet cell count was closely monitored within and after the PSMA-RLT and analyzed statistically and according to CTCAE.

Results

No significant difference in platelet counts was observed between baseline and follow-up after each PSMA-RLT cycle: first cycle (54.18 ± 16.07 at baseline vs. 59.65 ± 39.16 at follow up [in × 10⁹/L], p= 0.834), second cycle (58.56 ± 16.43 vs. 107.1 ± 56.44, p = 0.203), and third cycle (60.38 ± 16.57 vs. 132.1 ± 80.43, p = 0.148), respectively. Similarly, baseline and end of treatment values, irrespective of the number of administered cycles, did not reveal a significant difference (54.18 ± 16.07 vs. 72.06 ± 71.9, p = 0.741). After the end of therapy, irrespective of the number of administered cycles, 29.4% of patients remained stable in terms of CTCAE scoring, 41.2% changed to a higher score and 29.4% improved to a lower score. We observed no critical bleeding events due to thrombocytopenia.

Conclusion

Despite the common consideration of marked preexisting thrombocytopenia as a contraindication for RLT, this study indicates feasibility of PSMA-RLT in patients with preexisting thrombocytopenia of grade ≥ 2, as in our preliminary experience, there was no RLT-induced significant deterioration of platelet cell count. Thus, patients with thrombocytopenia should not be categorically excluded from receiving PSMA-RLT.

Purpose

The objective of this study is to generate reliable K_i parametric images from a shortened [¹⁸F]FDG total-body PET for clinical applications using a self-supervised neural network algorithm.

Methods

We proposed a self-supervised neural network algorithm with Patlak graphical analysis (SN-Patlak) to generate K_i images from shortened dynamic [¹⁸F]FDG PET without 60-min full-dynamic PET-based training. The algorithm deeply integrates neural network architecture with a Patlak method, employing the fitting error of the Patlak plot as the neural network’s loss function. As the 0–60 min blood time activity curve (TAC) required by the standard Patlak plot is unobtainable from shortened dynamic PET scans, a population-based “normalized time” (integral-to-instantaneous blood concentration ratio) was used for the linear fitting of Patlak plot of t* to 60 min, and the modified Patlak plot equation was then incorporated into the neural network. K_i images were generated by minimizing the difference between the input layer (measured tissue-to-blood concentration ratios) and the output layer (predicted tissue-to-blood concentration ratios). The effects of t* (20 to 50 min post injection) on the K_i images generated from the SN-Patlak and standard Patlak was evaluated using the normalized mean square error (NMSE), and Pearson’s correlation coefficient (Pearson’s r).

Results

The K_i images generated by the SN-Patlak are robust to the dynamic PET scan duration, and the K_i images generated by the SN-Patlak from just a 10-minute (50–60 min post-injection) dynamic [¹⁸F]FDG total-body PET scan are comparable to those generated by the standard Patlak method from 40-min (20–60 min post injection) with NMSE = 0.15 ± 0.03 and Pearson’s r = 0.93 ± 0.01.

Conclusions

The SN-Patlak parametric imaging algorithm is robust and reliable for quantification of 10-min dynamic [¹⁸F]FDG total-body PET.

Purpose: [¹⁸F]SynVesT-1 is a novel radiopharmaceutical for assessing synaptic density in vivo. This study aims to investigate the potential of [¹⁸F]SynVesT-1 positron emission tomography (PET) in evaluating neurological recovery in the rat model of ischemic stroke, and to compare its performance with [¹⁸F]FDG PET.

Methods: Sprague-Dawley rats were subjected to photothrombotic cerebral infarction, and safinamide was administered intraperitoneally from day 3 to day 14 post-stroke to alleviate neurological deficits. Cylinder test and forelimb placing test were performed to assess the neurological function. MRI, [¹⁸F]SynVesT-1 PET/CT and [¹⁸F]FDG PET/CT imaging were used to evaluate infarct volume, synaptic density, and cerebral glucose metabolism pre- and post-treatment. [¹⁸F]SynVesT-1 and [¹⁸F]FDG PET images were compared using Statistical Parametric Mapping (SPM) and region of interest (ROI)-based analysis. Post-mortem histological analysis was performed to validate PET images.

Results: Safinamide treatment improved behavioral outcomes in stroke-damaged rats. Both [¹⁸F]SynVesT-1 and [¹⁸F]FDG PET detected stroke-induced injury, with the injured region being significantly larger in [¹⁸F]FDG PET than in [¹⁸F]SynVesT-1 PET. Compared with the saline group, radiotracer uptake in the injured area significantly increased in [¹⁸F]SynVesT-1 PET after safinamide treatment, whereas no notable change was observed in [¹⁸F]FDG PET. Additionally, [¹⁸F]SynVesT-1 PET imaging showed a better correlation with neurological function recovery than [¹⁸F]FDG PET. Post-mortem analysis revealed increased neuronal numbers, synaptic density, and synaptic neuroplasticity, as well as decreased glia activation in the stroke-injured area after treatment.

Conclusion: [¹⁸F]SynVesT-1 PET effectively quantified spatiotemporal dynamics of synaptic density in the rat model of stroke, and showed different capabilities in detecting stroke injury and neurological recovery compared with [¹⁸F]FDG PET. The utilization of [¹⁸F]SynVesT-1 PET holds promise as a potential non-invasive biomarker for evaluating ischemic stroke in conjunction with [¹⁸F]FDG PET.

Purpose: Positron emission tomography (PET) imaging of mutant huntingtin (mHTT) aggregates is a potential tool to monitor disease progression as well as the efficacy of candidate therapeutic interventions for Huntington's disease (HD). To date, the focus has been mainly on the investigation of ¹¹C radioligands; however, favourable ¹⁸F radiotracers will facilitate future clinical translation. This work aimed at characterising the novel [¹⁸F]CHDI-650 PET radiotracer using a combination of in vivo and in vitro approaches in a mouse model of HD.

Methods: After characterising [¹⁸F]CHDI-650 using in vitro autoradiography, we assessed in vivo plasma and brain radiotracer stability as well as kinetics through dynamic PET imaging in the heterozygous (HET) zQ175DN mouse model of HD and wild-type (WT) littermates at 9 months of age. Additionally, we performed a head-to-head comparison study at 3 months with the previously published [¹¹C]CHDI-180R radioligand.

Results: Plasma and brain radiometabolite profiles indicated a suitable metabolic profile for in vivo imaging of [¹⁸F]CHDI-650. Both in vitro autoradiography and in vivo [¹⁸F]CHDI-650 PET imaging at 9 months of age demonstrated a significant genotype effect (p < 0.0001) despite the poor test-retest reliability. [¹⁸F]CHDI-650 PET imaging at 3 months of age displayed higher differentiation between genotypes when compared to [¹¹C]CHDI-180R.

Conclusion: Overall, [¹⁸F]CHDI-650 allows for discrimination between HET and WT zQ175DN mice at 9 and 3 months of age. [¹⁸F]CHDI-650 represents the first suitable ¹⁸F radioligand to image mHTT aggregates in mice and its clinical evaluation is underway.

Purpose: Bone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality.

Methods: This prospective cohort study included 94 ATTRwt amyloidosis patients and 26 amyloid-negative heart failure controls who underwent whole-body [^99mTc]Tc-hydroxydiphosphonate scintigraphy. Site-to-background ratios were calculated for heart, elbows, subcutaneous tissue, shoulders and wrists on anterior planar bone scintigraphy images using rib and whole-body radiotracer uptake as background. Fat tissue aspirates were stained with Congo red to grade amyloid load. Site-to-rib ratios were compared between ATTRwt amyloidosis patients and controls, and associations of site-to-background ratio with Congo red score and all-cause mortality were studied.

Results: ATTRwt amyloidosis patients had higher soft tissue-to-rib, heart-to-rib and heart-to-whole body ratios compared with controls. The intensity of soft tissue uptake was positively associated with amyloid load in fat tissue in ATTRwt amyloidosis patients. Estimated glomerular filtration rate, N-terminal brain natriuretic propeptide, high-sensitivity cardiac troponin T (hs-cTnT), and the prognostic Mayo and NAC staging system were associated with all-cause mortality in univariable models. Soft tissue/rib ratio, hs-cTnT and the prognostic staging systems were the only two variables that were independently associated withall-cause mortality.

Conclusion: Soft tissue radiotracer uptake on bone scintigraphy in ATTRwt amyloidosis patients is positively associated with amyloid load in abdominal fat tissue and is independently associated with mortality.

Introduction: Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors. It predominantly affects younger women and is associated with a poor prognosis. This systematic review aims to evaluate the current role of positron emission tomography (PET) in the management of TNBC patients and to identify future research directions.

Methods: We systematically searched the PubMed, Scopus, and Web of Science databases up to February 2024. A team of five researchers conducted data extraction and analysis. The quality of the selected studies was assessed using a specific evaluation form.

Results: Twenty-eight studies involving 2870 TNBC patients were included in the review. Key clinical applications of PET in TNBC included predicting pathological complete response (pCR) in patients undergoing neoadjuvant chemotherapy (NAC), assessing the prognostic value of baseline PET, and initial disease staging. Two studies utilized PSMA-ligand agents, while the majority used [¹⁸F]FDG-based PET. Significant associations were found between baseline [18F]FDG uptake and molecular biomarkers such as PDL-1, androgen receptor, and Ki67. Baseline [¹⁸F]FDG PET led to the upstaging of patients from stage IIB to stage IV, influencing treatment decisions and survival outcomes. In the NAC setting, serial PET scans measuring changes in [¹⁸F]FDG uptake, indicated by maximum standardized uptake value (SUVmax), predicted pCR with varying cut-off values correlated with different response rates. Semiquantitative parameters such as metabolic tumor volume (MTV) and PET lung index were prognostic for metastatic disease.

Conclusions: In TNBC patients, [¹⁸F]FDG PET is essential for initial disease staging in both localized and metastatic settings. It is also useful for assessing treatment response to NAC. The ability of PET to correlate metabolic activity with molecular markers and predict treatment outcomes highlights its potential in TNBC management. Further prospective studies are needed to refine these clinical indications and establish its definitive role.

Introduction: The unique expression pattern of fibroblast activation protein (FAP) in stromal and tumor cells, particularly in sarcomas, and its absence in normal tissues, have positioned it as a promising theragnostic approach for the detection and treatment of various cancer types. The objective of this prospective study is to assess the feasibility, safety, biodistribution, and therapeutic efficacy of [¹⁷⁷Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma.

Patients and methods: Eight patients with advanced metastatic sarcoma, who were unresectable or had experienced disease recurrence following conventional treatments, underwent PTRT (peptide-targeted radionuclide therapy) using [¹⁷⁷Lu]Lu-FAPI-2286. Prior to the treatment, confirmation of tumor uptake was obtained through [⁶⁸Ga]Ga-FAPI-2286 PET/CT.

Results: After four cycles of PTRT with [¹⁷⁷Lu]Lu-FAPI-2286 (6660-7400 MBq), with a 6-8-week interval between each cycle, no grade 3 or 4 side effects were observed in the patients, and the treatment was well tolerated by all participants. The results demonstrated a 52.37% reduction in the average volume of the primary tumor, accompanied by a significant decrease in SUV_max and TBR of the metastatic lesions (29.67% and 43.66% respectively), especially in cases of lung metastasis. Furthermore, besides the improvement in physical capacity, there was a noticeable reduction in pain, an increase in overall survival, and enhanced satisfaction with the treatment reported by the patients.

Conclusion: [¹⁷⁷Lu]Lu-FAPI-2286 PTRT, utilized for diverse cancer types, exhibited favorable tolerability in sarcoma patients, with minimal side effects, long-lasting retention of the radiopeptide within the tumor, and promising therapeutic effects. Preliminary findings of this prospective study need to be confirmed through further clinical trials.

Purpose: [¹⁸F]SynVesT-1, a positron emission tomography (PET) radiotracer for the synaptic vesicle glycoprotein 2A (SV2A), demonstrates kinetics similar to [¹¹C]UCB-J, with high brain uptake, fast kinetics fitting well with the one-tissue compartment (1TC) model, and excellent test-retest reproducibility. Challenges arise due to the similarity between k₂ and [Formula: see text] (efflux rate of the reference region), when applying the simplified reference tissue model (SRTM) and related methods in [¹¹C]UCB-J studies to accurately estimate [Formula: see text]. This study evaluated the suitability of these methods to estimate [¹⁸F]SynVesT-1 binding using centrum semiovale (CS) or cerebellum (CER) as reference regions.

Method: Seven healthy participants underwent 120-min PET scans on the HRRT scanner with [¹⁸F]SynVesT-1. Six participants underwent test and retest scans. Arterial blood sampling and metabolite analysis provided input functions for the 1TC model, serving as the gold standard for kinetic parameters values. SRTM, coupled SRTM (SRTMC) and SRTM2 estimated were applied to estimate [Formula: see text](ref: CS) and DVR_CER(ref: CER) values. For SRTM2, the population average of [Formula: see text] was determined from the 1TC model applied to the reference region. Test-retest variability and minimum scan time were also calculated.

Results: The 1TC k₂ (1/min) values for CS and CER were 0.031 ± 0.004 and 0.021 ± 0.002, respectively. Although SRTMC [Formula: see text] was much higher than 1TC [Formula: see text], SRTMC underestimated BP_ND(ref: CS) and DVR_CER by an average of 3% and 1% across regions, respectively, due to similar bias in k₂ and [Formula: see text] estimation. SRTM underestimated BP_ND(ref: CS) by an average of 3%, but with the CER as reference region, SRTM estimation was unstable and DVR_CER underestimation varied by region (mean 10%). Using population average [Formula: see text] values, SRTM2 BP_ND and DVR_CER showed the best agreement with 1TC estimates.

Conclusion: Our findings support the use of population [Formula: see text] value in SRTM2 with [¹⁸F]SynVesT-1 for the estimation of [Formula: see text] or DVR_CER, regardless of the choice of reference region.