European Journal of Nuclear Medicine and Molecular Imaging最新文献

Purpose: To assess if PSMA PET quantitative parameters are associated with pathologic ISUP grade group (GG) and upgrading/downgrading.

Methods: PCa patients undergoing radical prostatectomy with or without pelvic lymph node dissection staged with preoperative PSMA PET at seven referral centres worldwide were evaluated. PSMA PET parameters which included SUV_max, PSMA_volume, and total PSMA accumulation (PSMA_total) were collected. Multivariable logistic regression evaluated the association between PSMA PET quantified parameters and surgical ISUP GG. Decision-tree analysis was performed to identify discriminative thresholds for all three parameters related to the five ISUP GGs The ROC-derived AUC was used to determine whether the inclusion of PSMA quantified parameters improved the ability of multivariable models to predict ISUP GG ≥ 4.

Results: A total of 605 patients were included. Overall, 2%, 37%, 37%, 10% and 13% patients had pathologic ISUP GG1, 2, 3, 4, and 5, respectively. At multivariable analyses, all three parameters SUV_max, PSMA_volume and PSMA_total were associated with GG ≥ 4 at surgical pathology after accounting for PSA and clinical T stage based on DRE, hospital and radioligand (all p < 0.05). Addition of all three parameters significantly improved the discrimination of clinical models in predicting GG ≥ 4 from 68% (95%CI 63 - 74) to 74% (95%CI 69 - 79) for SUV_max, 72% (95%CI 67 - 76) for PSMA_volume, 74% (70 - 79) for PSMA_total and 75% (95%CI 71 - 80) when all parameters were included (all p < 0.05). Decision-tree analysis resulted in thresholds that discriminate between GG (SUV_max 0-6.5, 6.5-15, 15-28, > 28, PSMA_vol 0-2, 2-9, 9-20 and > 20 and PSMA_total 0-12, 12-98 and > 98). PSMA_volume was significantly associated with GG upgrading (OR 1.03 95%CI 1.01 - 1.05). In patients with biopsy GG1-3, PSMA_volume ≥ 2 was significantly associated with higher odds for upgrading to ISUP GG ≥ 4, compared to PSMA_volume < 2 (OR 6.36, 95%CI 1.47 - 27.6).

Conclusion: Quantitative PSMA PET parameters are associated with surgical ISUP GG and upgrading. We propose clinically relevant thresholds of these parameters which can improve in PCa risk stratification in daily clinical practice.

Purpose: NB12 is a bispecific antibody that consists of two anti-programmed cell death-ligand 1 (PD-L1) nanobodies and two anti-programmed cell death-ligand 2 (PD-L2) nanobodies. The aim of this study was to design a novel tracer, [¹²⁴I]I-NB12, targeting PD-L1/2 and perform preclinical evaluations to dynamically monitor PD-L1/2 expression for determining cancer patient responsiveness to ICI therapy.

Methods: NB12 was labelled with the radionuclide ¹²⁴I at room temperature (RT). An in vitro binding assay was performed to assess the affinity of [¹²⁴I]I-NB12 for PD-L1 and PD-L2. Cellular uptake, pharmacokinetic, and biodistribution experiments were performed to evaluate the biological properties. Micro-PET/CT imaging with [¹²⁴I]I-NB12 was conducted at different time points. Immunohistochemical and haematoxylin and eosin (HE) staining experiments were carried out using tumour tissues. Routine blood, biochemical indices and major organ pathology were used to evaluate the biosafety of the tracers.

Results: The radiochemical yield of [¹²⁴I]I-NB12 was 84.62 ± 3.90%, and the radiochemical purity (RCP) was greater than 99%. [¹²⁴I]I-NB12 had a high affinity for the PD-L1 (Kd = 19.82 nM) and PD-L2 (Kd = 2.93 nM). Cellular uptake experiments confirmed that the uptake of [¹²⁴I]I-NB12 by A549-PDL1/2 cells was greater than that by A549 cells. The half-lives of the distribution phase and elimination phase were 0.26 h and 4.08 h, respectively. Micro-PET/CT showed significant [¹²⁴I]I-NB12 uptake in the tumour region of A549-PDL1/2 tumour-bearing mice compared with A549 tumour-bearing mice 24 h postinjection. Immunohistochemical and HE staining experiments confirmed that tumour-bearing mice was successfully constructed.

Conclusion: We constructed a bispecific antibody that targets PD-L1 and PD-L2, namely, [¹²⁴I]I-NB12. Biological evaluation revealed its specificity and affinity for PD-L1/2, and micro-PET/CT confirmed the feasibility of visualizing tumour PD-L1/2 in vivo. Using [¹²⁴I]I-NB12 may be a promising strategy for identifying cancer patients that can potentially benefit from ICI therapy.

Background: The purpose of this study was to evaluate the safety and outcome of rechallenge [¹⁷⁷Lu]Lu-PSMA-I&T in newly progressed mCRPC patients after response to initial [¹⁷⁷Lu]Lu-PSMA radioligand therapy (PRLT).

Methods: We retrospectively included 18 patients who underwent rechallenge with [¹⁷⁷Lu]Lu-PSMA-I&T. All patients presented with (i) newly progressed disease after response to initial PRLT; (ii) a [⁶⁸Ga]Ga-PSMA-11 PET/CT confirming the presence of PSMA-positive metastases; iii) ECOG performance status 0-1. Adverse events were graded according to CTCAE v5.0. Response was assessed by PSA and classified according to PCWG3 recommendations. For patients who underwent restaging with [⁶⁸Ga]Ga-PSMA-11 PET/CT, imaging response was categorised according to adapted PERCIST v1.0. In patients with discordant [⁶⁸Ga]Ga-PSMA-11 PET/CT and PSA, other available imaging modalities were evaluated to confirm disease status. Overall survival (OS) was calculated from the first cycle of initial PRLT and rechallenge PRLT, respectively, until last patient contact or death.

Results: Patients were initially treated with a median of 5 cycles (range 4-7) and were rechallenged after a median of 9 months (range 3-13). Each patient received a median of 4 (range 2-7) rechallenge cycles (median cumulative activity 26.1 GBq). None of the patients experienced life-threatening G4 adverse events during either treatment period. Grade 3 adverse events included one case of anaemia, one case of thrombocytopenia, and one case of renal failure. In 8/18 patients long-term toxicities were evaluated. Serious toxicities (≥ Grade 3) occurred in 3/8 patients (n = 1 G4 thrombocytopenia, n = 1 G4 renal failure and n = 1 pancytopenia and G4 renal failure). Best PSA50%-response was observed in 44% of patients and PSA-disease control was confirmed in 56% of patients at the last cycle. Of the 12/18 patients restaged by imaging, 6/12 (50%) patients had disease control (partial response/stable disease), 1/12 had a mixed response, and 5/12 had progression. After a median follow-up time of 25 months (range 14-44), 10 patients had died, 7 were still alive, and one patient was lost at follow-up. The median OS was 29 months (95%CI, 14.3-43.7 months) for the initial treatment and 11 months (95%CI, 8.1-13.8 months) for the first rechallenge course.

Conclusion: More than half of patients benefit from rechallenge PRLT. Our analysis suggests that rechallenge may prolong survival in selected patients, with an acceptable safety profile.

Purpose: In this systematic review and individual patient data (IPD) meta-analysis, we analysed the diagnostic performance of [¹⁸F]FDG PET/CT in detecting primary tumours in patients with CUP and evaluated whether the location of the predominant metastatic site influences the diagnostic performance.

Methods: A systematic literature search from January 2005 to February 2024 was performed to identify articles describing the diagnostic performance of [¹⁸F]FDG PET/CT for primary tumour detection in CUP. Individual patient data retrieved from original articles or obtained from corresponding authors were grouped by the predominant metastatic site. The diagnostic performance of [¹⁸F]FDG PET/CT in detecting the underlying primary tumour was compared between predominant metastatic sites.

Results: A total of 1865 patients from 32 studies were included. The largest subgroup included patients with predominant bone metastases (n = 622), followed by liver (n = 369), lymph node (n = 358), brain (n = 316), peritoneal (n = 70), lung (n = 67), and soft tissue (n = 23) metastases, leaving a small group of other/undefined metastases (n = 40). [¹⁸F]FDG PET/CT resulted in pooled detection rates to identify the primary tumour of 0.74 (for patients with predominant brain metastases), 0.54 (liver-predominant), 0.49 (bone-predominant), 0.46 (lung-predominant), 0.38 (peritoneal-predominant), 0.37 (lymph node-predominant), and 0.35 (soft-tissue-predominant).

Conclusion: This individual patient data meta-analysis suggests that the ability of [¹⁸F]FDG PET/CT to identify the primary tumour in CUP depends on the distribution of metastatic sites. This finding emphasises the need for more tailored diagnostic approaches in different patient populations. In addition, alternative diagnostic tools, such as new PET tracers or whole-body (PET/)MRI, should be investigated.

Purpose: Lewy body dementia (LBD) is a neurodegenerative disease with high heterogeneity and complex pathogenesis. Our study aimed to use disease progression modeling to uncover spatial-temporal dynamic evolution of LBD in vivo, and to explore differential profiles of clinical features, glucose metabolism, and dopaminergic function among different evolution-related subtypes.

Methods: A total of 123 participants (31 healthy controls and 92 LBD patients) who underwent ¹⁸F-FDG PET scans were retrospectively enrolled. ¹⁸F-FDG PET-based Subtype and Stage Inference (SuStaIn) model was established to illustrate spatial-temporal evolutionary patterns and categorize relevant subtypes. Then subtypes and stages were further related to clinical features, glucose metabolism, and dopaminergic function of LBD patients.

Results: This ¹⁸F-FDG PET imaging-based approach illustrated two distinct patterns of neurodegenerative evolution originating from the neocortex and basal ganglia in LBD and defined them as subtype 1 and subtype 2, respectively. There were obvious differences between subtypes. Compared with subtype 1, subtype 2 exhibited a greater proportion of male patients (P = 0.045) and positive symptoms such as visual hallucinations (P = 0.033) and fluctuating cognitions (P = 0.033). Cognitive impairment, metabolic abnormalities, dopaminergic dysfunction and progression were all more severe in subtype 2 (all P < 0.05). In addition, a strong association was observed between SuStaIn subtypes and two clinical phenotypes (Parkinson's disease dementia and dementia with Lewy bodies) (P = 0.005).

Conclusions: Our findings based on ¹⁸F-FDG PET and data-driven model illustrated spatial-temporal dynamic evolution of LBD and categorized novel subtypes with different evolutionary patterns, clinical and imaging features in vivo. The evolution-related subtypes are associated with LBD clinical phenotypes, which supports the perspective of existence of distinct entities in LBD spectrum.

Purpose: Pulmonary fibrosis is an irreversible scar-forming condition for which there is a lack of non-invasive and specific methods for monitoring its progression and therapy efficacy. However, the disease is known to be accompanied by collagen accumulation. Here, we developed a novel positron emission tomography (PET) probe targeting type I collagen to evaluate its utility for the non-invasive assessment of pulmonary fibrosis.

Methods: We designed a ¹⁸F-labeled PET probe ([¹⁸F]AlF-CBP) to target type I collagen and evaluated its binding affinity, specificity and stability in vitro. PET with [¹⁸F]AlF-CBP, CT, histopathology, immunofluorescence, and biochemical indice were performed to assess and quantify type I collagen levels and pulmonary fibrosis progression and treatment in murine models. Dynamic PET/CT studies of [¹⁸F]AlF-CBP were conducted to assess lung fibrosis in non-human primate models.

Results: [¹⁸F]AlF-CBP was successfully prepared, and in vitro and in vivo tests showed high stability (> 95%) and type I collagen specificity (IC₅₀ = 0.36 µM). The lungs of the fibrotic murine model showed more elevated probe uptake and retention compared to the control group, and there was a positive correlation between the radioactivity uptake signals and the degree of fibrosis (CT: R² = 0.89, P < 0.0001; hydroxyproline levels: R² = 0.89, P < 0.0001). PET signals also correlated well with mean lung density in non-human primate models of pulmonary fibrosis (R² = 0.84, P < 0.0001).

Conclusion: [¹⁸F]AlF-CBP PET imaging is a promising non-invasive method for specific monitoring of lung fibrosis progression and therapy efficacy.

Purpose: This prospective study aims to evaluate the value of [¹⁸F]AlF-NOTA-fibroblast activation protein inhibitor (FAPI)-04 positron emission tomography-computed tomography (PET/CT) in predicting molecular subtypes of breast cancer.

Methods: The study consecutively recruited patients suspected of having breast cancer from a single center who were prospectively enrolled from July 2023 to May 2024 and underwent [¹⁸F]AlF-NOTA-FAPI-04 PET/CT. This study compared the differences in tracer uptake among breast cancers with different adverse prognostic factors and molecular subtypes. The classification performance for each molecular subtype of breast cancer was assessed using a receiver operating characteristic (ROC) curve.

Results: Fifty-three participants (mean age, 51 ± 11 years; 52 females) were evaluated. Breast cancer lesions with adverse prognostic factors showed higher tracer uptake. The five different molecular subtypes exhibited varying levels of uptake. The luminal A and luminal B (HER2-negative) subtypes had relatively low uptake, while the luminal B (HER2-positive), HER2-positive, and triple-negative subtypes had relatively high uptake. ROC analysis identified the max standardized uptake value (SUV_max) as a significant classifier (AUC = 0.912, P = 0.0005) for the luminal A subtype, with 100% sensitivity and 83% specificity. For predicting the luminal B (HER2-negative) subtype, SUV_max had an AUC of 0.770 (P = 0.0015). SUV_max, with an AUC of 0.781 (P = 0.003), was used to identify the triple-negative subtype tumors, resulting in a sensitivity of 100% and specificity of 51%. Lastly, the ROC curve showed the cut-off 15.40 (AUC = 0.921, P < 0.0001) could classify luminal A & luminal B (HER2-negative), and luminal B (HER2-positive) & HER2-positive & triple-negative, yielding a sensitivity of 94% and specificity of 79%.

Conclusion: The uptake of [¹⁸F]AlF-NOTA-FAPI-04 is significantly correlated with the molecular subtypes of breast cancer, and [¹⁸F]AlF-NOTA-FAPI-04 PET/CT is a potential tool for noninvasive identification of luminal A subtypes and guidance of FAP-targeted therapies.