ObjectiveTo investigate whether baseline 18F-FDG PET/CT immune-organ metabolic features are associated with immune-related adverse events (irAEs) in non-small cell lung cancer (NSCLC) patients receiving anti-PD-1 therapy.MethodsWe retrospectively analyzed 120 stage III–IV NSCLC patients who underwent 18F-FDG PET/CT within 4 weeks before anti-PD-1 therapy and received ≥2 treatment cycles. The endpoint was any-grade irAE (CTCAE v5.0). Candidate predictors included tumor burden; spleen, bone-marrow, and thyroid metabolism; spleen-to-liver ratio (SLR); and bone-marrow-to-liver ratio. Standardized variables entered multivariable logistic regression with bootstrap optimism correction (1,000 resamples) and sensitivity analyses.ResultsirAEs occurred in 66 patients (55.0%) after a median of 61.5 days; 18 (27.3%) had grade 3–4 events, mainly pneumonitis and hepatitis. Compared with non-irAE patients, irAE patients showed higher SLR, spleen SUVmax, bone-marrow indices, thyroid SUVmax, and neutrophil-to-lymphocyte ratio (NLR). In the final multivariable model, SLR (odds ratio [OR] 4.13 per 1-SD; 95% CI, 2.28–7.49; p < 0.001), thyroid SUVmax (OR 3.57; 95% CI, 1.96–6.49; p < 0.001), and NLR (OR 2.00; 95% CI, 1.24–3.24; p = 0.005) were independently associated with irAEs. Model AUC was 0.863 (optimism-corrected, 0.850), and persisted after excluding thyroiditis-first cases (AUC 0.874). Discrimination was lower when grade 3–4 events were used as the outcome (AUC 0.724), indicating that the model predicted any-grade irAEs more accurately than severe events.ConclusionBaseline splenic and thyroid FDG metabolism, combined with systemic inflammation, were independently associated with irAEs in anti-PD-1-treated NSCLC, providing candidate pretreatment risk-stratification markers pending external validation.

Postoperative staging and residual/metastatic lesion detection of papillary thyroid cancer (PTC) before radioiodine (RAI) ablation remains a critical clinical demand, especially for patients with intermediate to high-risk pathological features. Although 2-[18F] fluoro-2-deoxy-D-glucose ([18F] FDG) positron emission tomography/computed tomography (PET/CT) is widely applied in thyroid cancer imaging, its diagnostic sensitivity is suboptimal for small-volume, low-metabolic metastatic or residual lesions. Fibroblast activation protein (FAP), specifically overexpressed in tumor stromal cancer-associated fibroblasts (CAFs), has become a novel and reliable imaging target for oncological detection. This study aimed to head-to-head compare the diagnostic efficacy of [18F]AL-NOTA-FAPI-46 ([18F] FAPI-46) and [¹⁸F] FDG PET/CT in identifying postoperative residual and lymph node metastatic lesions in PTC patients prior to adjuvant ¹³¹I therapy. A total of 18 consecutive postoperative PTC patients scheduled for ¹³¹I ablation were prospectively enrolled. All patients underwent paired [18F] FAPI-46 and [18F] FDG PET/CT within a 1-week interval before treatment. A composite reference standard integrating histopathological results, standardized imaging follow-up (median follow-up duration: 8 months, range: 6–12 months) and continuous clinical serological monitoring was adopted to verify lesion properties. Two experienced nuclear medicine physicians independently and blindly interpreted all PET/CT images in random order, with consensus arbitration for discrepant results. Quantitative imaging parameters including SUVmax and SUVpeak were calculated for all target lesions. For lymph node metastatic lesion detection, [18F] FAPI-46 PET/CT exhibited significantly higher sensitivity (82.3

This case report describes an 81-year-old man with primary high-grade urothelial carcinoma of the prostate, which presented with a negative 18 F-PSMA PET/CT. Contrast-enhanced prostate MRI initially suggested a malignant lesion; however, 18 F-PSMA PET/CT revealed no significant tracer uptake. Postoperative immunohistochemical analysis demonstrated positivity for urothelial markers GATA3 and CK7, while prostate-specific markers PSA and AR were negative, confirming the diagnosis of primary high-grade urothelial carcinoma of the prostate. This case indicates that a negative PSMA PET/CT scan may serve as an important diagnostic clue in distinguishing non-adenocarcinomatous prostate malignancies.

IntroductionImmune checkpoint inhibitors (ICI) effectively treat advanced cutaneous squamous cell carcinoma (cSCC), yet some patients continue to have disease progression. Combining radiation therapy (RT) with ICI represents a potential therapeutic option, yet limited data exist regarding oncologic outcomes and safety profile.MethodsThis retrospective cohort study examined patients treated with concurrent ICI and RT between April 2019 and November 2022 and stratified by locally advanced or metastatic status. Outcomes included locoregional control (LRC), freedom from distant metastases (FFDM), progression-free survival (PFS), overall survival (OS), and toxicity. Statistical analysis was performed using Kaplan-Meier or Fine-Gray competing risk survival analyses.ResultsThirteen patients (median age 77 years) with locally advanced (53.8%) or metastatic (46.2%) cSCC on cemiplimab (84.6%) or pembrolizumab (15.4%) received concomitant RT using intensity-modulated radiotherapy (69.2%) or stereotactic body radiotherapy (30.8%). With median follow-up of 15.4 months, overall 1-year and 2-year outcomes were OS: 75.2% and 62.7%; PFS: 59.8% and 25.6%; FFDM: 83.8% and 62.4%; LRC 100% and 84.3%, respectively. Locally advanced patients had significantly greater LRC than metastatic patients (100% vs. 56.3%; p<0.001), but no significant difference in PFS, FFDM, or OS. Only one patient experienced grade 3 radiation dermatitis, with no grade 4+ toxicities.ConclusionRadioimmunotherapy demonstrated favorable oncologic outcomes with minimal toxicity. Addition of consolidative RT to ICI therapy may represent a safe and effective approach for this challenging patient population, warranting further prospective investigation.

Abstract Background Programmed cell death 1/programmed death ligand-1 (PD-L1)-based immune checkpoint blockade is an effective treatment approach for non-small-cell lung cancer (NSCLC). However, immunohistochemistry does not accurately or dynamically reflect PD-L1 expression owing to its spatiotemporal heterogeneity. Herein, we assessed the feasibility of using a 68Ga-labeled anti-PD-L1 nanobody, 68Ga-NODAGA-NM-01, for PET imaging of PD-L1. Methods Micro-PET/CT and biodistribution studies were performed on PD-L1-positive and -negative tumor-bearing mice. Additionally, a preliminary clinical study was performed on two patients with NSCLC. NM-01 was radiolabeled with 68Ga without further purification under mild conditions. Results 68Ga-NODAGA-NM-01 exhibited radiochemical purity (> 98%), high stability in vitro, and rapid blood clearance in vivo. Specific accumulation of 68Ga-NODAGA-NM-01 was observed in PD-L1-positive tumor-bearing mice, with a good tumor-to-background ratio 0.5h post-injection. Furthermore, 68Ga-NODAGA-NM-01 PET/CT imaging was found to be safe with no adverse events and distinct uptake in primary and metastatic lesions of the PD-L1-positive patient, with a higher maximal standardized uptake value than that in lesions of the PD-L1-negative patient 1h post-injection. Conclusions 68Ga-NODAGA-NM-01 can be prepared using a simple method under mild conditions and reflect PD-L1 expression in primary and metastatic lesions. However, our findings need to be confirmed in a large cohort. Trial registration NCT02978196. Registered February 15, 2018.

ABSTRACT Objective To compare the predictive value of the estimated dose of radiation to immune cells (EDRIC) with conventional dosimetric parameters for survival in elderly patients with stage III unresectable NSCLC after chemoimmunotherapy and radiotherapy. Methods We conducted a retrospective study of elderly patients (≥ 65 years) treated at two institutions. Patients were stratified by median EDRIC, mean lung dose (MLD), mean heart dose (MHD), and mean body dose (MBD). Survival was analyzed using Kaplan–Meier, Cox regression, and ROC curves. Results Baseline characteristics were well‐balanced across dosimetric parameter subgroups (all p > 0.05). The median progression‐free survival (PFS) and overall survival (OS) for the entire cohort were 23.9 months and 46.0 months, respectively. EDRIC ≥ 6.4 Gy was associated with worse PFS (p = 0.019) and OS (p = 0.011), while MLD, MHD, and MBD showed no prognostic significance (all p > 0.05). Multivariate analysis identified EDRIC ≥ 6.4 Gy as an independent predictor of worse PFS (HR = 1.852, p = 0.049) and OS (HR = 2.289, p = 0.048). Age ≥ 70 years was also independently associated with poorer OS (HR = 2.870, p = 0.011). ROC analysis demonstrated superior predictive performance of EDRIC over conventional parameters for 1‐, 2‐, and 3‐year PFS and OS, with particularly outstanding discrimination for 12‐month OS (AUC = 0.93). Conclusion EDRIC shows potential in predicting survival for elderly stage III unresectable NSCLC patients, with 6.4 Gy as a potential threshold for personalized radiotherapy optimization. These findings require prospective validation.

A deep progressive learning method for PET image reconstruction named deep progressive reconstruction (DPR) method was developed and presented in previous works. It has been shown in previous study that the DPR with one-third duration can maintain the image quality as OSEM with standard dose (3.7 MBq/kg). Subsequent studies have shown we can reduce the administered activity of 18F-FDG by up to 2/3 in a real-world deployment with DPR. The aim of this study is to assess the impact of the use of DPR on Deauville score (DS) and clinical interpretation of PET/CT in patients with lymphoma. A total of 87 lymphoma patients (age, 45.1 ± 14.9 years) who underwent 18F-FDG PET imaging for during or post-treatment follow-up from November 2020 to February 2024 were prospectively enrolled. The patients were randomly assigned to two groups, including the 1/3 standard dose group and the standard dose group. Forty-four patients were injected with 1/3 standard dose (1.23 MBq/kg) and scanned for 6 min per bed and were reconstructed: ordered-subsets expectation maximization (OSEM) with 6 min per bed (OSEM_6 min_1/3), OSEM_2 min_1/3 and DPR_2 min_1/3. Forty-three patients were scanned according to the standard protocol (3.7 MBq/kg) and were reconstructed: OSEM with 2 min per bed (OSEM_2 min_full), OSEM_40 s_full and DPR_40 s_full. Additionally, the conventional 5-point scale measurement analysis was performed and DS for lymphoma were determined in different groups. Wilcoxon signed-rank test was used to compare the mean values of liver SUVmax and mediastinal blood pool (MBP) SUVmax in each group. Likert scale and DS were evaluated using Wilcoxon signed rank test. The patients with OSEM_6 min_1/3 and DPR_2 min_1/3 showed good image quality with 5(5,5) and 5(4,5) of Likert scoring, as well as the patients with OSEM_2 min_full and DPR_40 s_full. No significant difference was found between the OSEM_6 min_1/3 and DPR_2 min_1/3 groups in terms of liver SUVmax and MBP SUVmax (P = 0.452 and 0.430), as well as the patients with OSEM_2 min_full and DPR_40 s_full (P = 0.105 and 0.638). No significant difference was found between the OSEM_6 min_1/3 and DPR_2 min_1/3 groups in terms of lesion SUVmax (P = 0.080). There was a significant differences in lesion SUVmax between OSEM-2 min_full with DPR-40 s_full (P = 0.027). The DS results were consistent (100

Background 99m Tc radiolabeled nanobody NM-02 ( 99m Tc-NM-02) is a novel single photon emission computed tomography (SPECT) probe with a high affinity and specificity for human epidermal growth factor receptor 2 (HER2). In this study, a clinical imaging trial was conducted to investigate the relationship between 99m Tc-NM-02 uptake and HER2 expression in patients with breast cancer. Methods Thirty patients with pathologically confirmed breast cancer were recruited and imaged with both 99m Tc-NM-02 SPECT/computed tomography (CT) and 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT. According to the treatment conditions before recruitment, patients were divided into two groups, the newly diagnosed group ( n = 24) and the treated group ( n = 6). The maximal standard uptake value (SUV max ) of 18 F-FDG and SUV max and mean SUV (SUV mean ) of 99m Tc-NM-02 in the lesions were determined to analyze the relationship with HER2 expression. Results No meaningful relationship was observed between 18 F-FDG uptake and HER2 expression in 30 patients with breast cancer. 99m Tc-NM-02 uptake was positively correlated with HER2 expression in the newly diagnosed group, but no correlation was observed in the treated group. 99m Tc-NM-02 uptake in HER2-positive lesions was lower in those with effective HER2-targeted therapy compared with the newly diagnosed group. 99m Tc-NM-02 SPECT/CT detected brain and bone metastases of breast cancer with a different imaging pattern from 18 F-FDG PET/CT. 99m Tc-NM-02 showed no non-specific uptake in inflamed tissues and revealed intra- and intertumoral HER2 heterogeneity by SPECT/CT imaging in 9 of the 30 patients with breast cancer. Conclusions 99m Tc-NM-02 SPECT/CT has the potential for visualizing whole-body HER2 overexpression in untreated patients, making it a promising method for HER2 assessment in patients with breast cancer. Trial registration NCT04674722, Date of registration: December 19, 2020.

ABSTRACT:A 27-year-old woman underwent 68 Ga-pentixafor PET/CT for primary aldosteronism localization and characterization. No functional adrenal nodules were detected by 68 Ga-pentixafor PET/CT, whereas a hypodense nodule with focal pentixafor uptake was incidentally discovered in the head of pancreas. Retrospective analysis of contrast-enhanced CT scan revealed a subtly enhancing nodule devoid of calcification in the pancreatic head. Pancreatic cancer cannot be excluded. 18 F-FDG PET/CT was suggested, and the scan showed an FDG-avid lesion in the same region. Needle biopsy was performed, and the pathological result is solid pseudopapillary tumor, a rare pancreatic tumor of low malignant potential.

Tumor immunotherapy represents a highly promising modality for the treatment of triple-negative breast cancer (TNBC). Nevertheless, its therapeutic efficacy has been profoundly impacted by challenges such as low drug uptake, hypoxia, and immunosuppression. To address these problems, the study develops a strategy combining sonodynamic therapy (SDT) and immunotherapy using biomimetic nanoparticles coated with hybrid membranes. The nanoparticles are loaded with semiconducting polymers (PFODBT), Atovaquone (ATO), and TMP195 to enhance biocompatibility, targeting ability, and drug uptake and retention at the tumor site. In in vitro experiments, the biomimetic nanoparticles alleviate hypoxia, induce immunogenic cell death (ICD), and prompt reprogramming of tumor-associated macrophages (TAMs) from M2 type to M1 type. In in vivo experiments, the synergistic effects of enhanced SDT-mediated ICD and TAMs repolarization significantly inhibit the proliferation of primary and distant tumor in the 4T1 subcutaneous tumor model, and effectively attenuated metastasis of lung and liver. Moreover, the in vivo immune responses are further activated by improving the maturation of dendritic cells, filtration of CD8+ T cells, and depletion of regulatory T cells. This study offers a novel strategy for TNBC therapy by converting the tumor microenvironment from the "cold" into "hot" tumor through multiple synergistic therapies.

SummaryMEK inhibitors have immunomodulatory activity and potential for synergistic activity when combined with PD-1 inhibitors. We evaluated selumetinib (inhibitor of MEK1/2) plus pembrolizumab (anti‒PD-1 antibody) in patients with advanced/metastatic solid tumors. In this phase 1b study, adults with previously treated advanced/metastatic solid tumors received pembrolizumab 200 mg intravenously every 3 weeks plus selumetinib on days 1‒14 per 3-week cycle (2 weeks on/1 week off); selumetinib dosing began at 50 mg orally twice daily with escalation in 25 mg increments for ≤ 35 cycles. Primary endpoints were dose-limiting toxicities (DLTs), adverse events (AEs), and treatment discontinuations due to AEs. Thirty-two patients were enrolled. Dose escalation was completed up to selumetinib 125 mg twice daily. The target DLT rate of 30% was not reached at any dose level. In the selumetinib 100 mg group, 2/11 patients (18.2%) experienced DLTs (n = 1 grade 3 diarrhea, n = 1 grade 3 fatigue). In the selumetinib 125 mg group, 3/14 (21.4%) experienced DLTs (n = 1 grade 2 retinal detachment, n = 1 grade 3 retinopathy, n = 1 grade 3 stomatitis). Dose-related changes in pharmacokinetic exposures were observed for selumetinib and N-desmethyl selumetinib up to 100 mg (saturation at 125 mg). Two patients achieved partial responses (1 each with selumetinib 75 mg and 125 mg) for an objective response rate of 6%. The study was stopped early because of insufficient efficacy. Although the target DLT rate was not reached at any dose level and no new safety signals were identified, selumetinib plus pembrolizumab had limited antitumor activity in this population. Trial registration: ClinicalTrials.gov, NCT03833427.

Purpose: This study evaluates the impact of Medicaid expansion under the Affordable Care Act (ACA) on melanoma staging at diagnosis, treatment utilization, and 3-year mortality outcomes. The objective is to determine whether Medicaid expansion led to earlier melanoma diagnosis and improved survival rates among non-elderly adults (ages 40-64) by analyzing data from the National Cancer Database (NCDB). Methods: A total of 12,667 patients, aged 40-64, diagnosed with melanoma from 2010 to 2020 were identified using the NCDB. Difference-in-difference (DID) analysis was performed to analyze tumor staging at presentation between Medicaid expansion states and non-Medicaid expansion states both prior to the expansion and after the expansion. Results: Of the total patients 2,307 were from the pre-expansion time period residing in Medicaid Expansion states (MES) and 1,804 in non-Medicaid expansion states. In the post-expansion time period there were 5,571 residing in the MES and 2,985 in the non-MES. DID analysis revealed a decrease in stage IV melanoma at diagnosis (DID -0.222, p <0.001) between MES and non-MES before and after Medicaid expansion. After expansion, in stage IV, the occurrence of primary surgery was 0.42 in non-MES and 0.44 (difference 0.02), DID analysis was not statistically significant. The use of immunotherapy in MES was significantly higher than non-MES after expansion (p<0.001), although DID analysis did not reveal a statistically significant difference. DID analysis showed a statistically significant decrease in 3-year mortality (DID -0.05, p=0.001) between MES and non-MES before and after Medicaid expansion. Conclusions: This study revealed the positive impact of the ACA’s Medicaid expansion on melanoma stage at presentation showing improved access to healthcare services can facilitate the diagnosis of early-stage melanoma and decrease mortality rate.

This study aimed to identify the prognostic value of interim 18F-FDG PET/CT (I-PET) for germinal center B-cell-like (GCB) and non-GCB diffuse large B-cell lymphoma (DLBCL), respectively. Baseline 18F-FDG PET/CT (B-PET) and I-PET scans were performed in 112 patients with DLBCL. The prognostic value of I-PET using the Deauville five-point scale (D-5PS) criteria or percentage decrease in SUVmax (∆SUVmax) for GCB and non-GCB DLBCL were evaluated. A significant difference in progression-free survival (PFS) was found between GCB and non-GCB DLBCL patients (P < 0.05). Based on D-5PS criteria, I-PET was divided into positive (score > 3) and negative (score ≤ 3) subgroups. Results indicated that I-PET using D-5PS criteria was an independent predictor for PFS of GCB DLBCL (P < 0.05), but not for overall survival (OS) (P > 0.05). For non-GCB DLBCL, PFS and OS were significantly higher in I-PET negative group than I-PET positive group (P < 0.05). Receiver operating characteristic (ROC) curve analysis proved that I-PET using ΔSUVmax can also effectively predict PFS and OS of non-GCB DLBCL (P < 0.05), but not for GCB DLBCL (P > 0.05). Based on the optimal threshold found by ROC curve analysis, patients were dichotomized into ∆SUVmax high and low groups. Log-rank test and Cox regression demonstrated that the layered ∆SUVmax was predictive of PFS and OS in non-GCB DLBCL (P < 0.05). I-PET may have different prognostic values for GCB and non-GCB DLBCL. Thus, the pathology type of DLBCL may be considered while using I-PET as a prognostic tool in the future.

Plectin, a scaffolding protein overexpressed in tumor cells, plays a significant role in hepatocellular carcinoma (HCC) proliferation, invasion, and migration. However, the use of L-type peptides for targeting plectin is hindered by their limited stability and retention. We designed a D-type plectin-targeting peptide (DPTP) and developed a novel single-photon emission computed tomography (SPECT) probe for HCC imaging. The DPTP targeting ability was evaluated in vitro using flow cytometry and ex vivo fluorescence imaging. 99mTc radiolabeling was performed using tricine and ethylenediamine-N,N '-diacetic acid (EDDA) as coligands after modification with 6-hydrazino nicotinamide (HYNIC) at the N termini of DPTP. The radiochemical purity (RCP), in vitro stability, and binding affinity of the prepared 99mTc-HYNIC-DPTP were analyzed. Tumor uptake, metabolic stability, biodistribution, and pharmacokinetics of 99mTc-HYNIC-DPTP were investigated and compared with those of 99mTc-labeled L-type PTP (99mTc-HYNIC-PTP) in HCC tumor-bearing mice. DPTP could be efficiently radiolabeled with 99mTc using the HYNIC/tricine/EDDA system with a high RCP and good in vitro stability. Compared with the L-type PTP, DPTP exhibited improved targeting ability, and 99mTc-HYNIC-DPTP displayed higher tumor uptake, better metabolic stability, longer blood circulation time, and lower kidney retention, resulting in superior imaging performance and biodistribution in vivo. 99mTc-HYNIC-DPTP has great potential as a novel SPECT probe for diagnosing HCC.

The landscape of melanoma treatment has undergone a dramatic revolution in the past decade. The use of oncolytic viruses (OVs) represents a novel therapeutic approach that can selectively infect and lyse tumor cells and induce local and systemic antitumor immune responses. As the first OV approved by the Food and Drug Administration (FDA) for melanoma treatment, talimogene laherparepvec (T-VEC), a genetically modified herpes simplex virus (HSV), has shown promising therapeutic effects in the treatment of advanced melanoma, both as a monotherapy or in combination with other immunotherapies, such as the immune checkpoint inhibitors (ICIs). With proven efficacy, T-VEC has been evaluated against a variety of other cancer types in a clinical trial setting. In this article, we will provide a review on OVs and the application of T-VEC in melanoma monotherapy and combination therapy. In addition, we will review the recent progress of T-VEC application in other cutaneous cancer types. Moreover, we will briefly describe our experience of T-VEC therapy at City of Hope, aiming to provide more insight for expanding its future application.

The prognostic value of interim 18F-FDG PET/CT (I-PET) for follicular lymphoma (FL) is controversial, and may be related to the lack of strict standards in terms of age, chemotherapy regimen, and evaluation criteria in previous studies. This study aimed to investigate the prognostic value of I-PET in adult FL patients treated with R-CHOP. I-PET was performed in 30 adult FL patients after treatment with 3–5 cycles of R-CHOP. PET/CT images were assessed using the Deauville 5-point scale (D-5PS) criteria. Baseline PET/CT (B-PET) was performed in 24 of the patients with FL before treatment. The PET/CT image parameters, such as the SUVmax, TLG, and tMTV, were recorded. The prognostic values of sex, age, grade, Ann Arbor stage, LDH level, and I-PET were evaluated. Kaplan-Meier analysis and Cox regression showed that sex, age, grade, Ann Arbor stage, LDH, and I-PET using the D-5PS criteria could not predict the PFS of adult patients with FL treated with R-CHOP (P>0.05). ROC curve analysis evaluated the predictive values of SUVmax, TLG, and tMTV in B-PET and I-PET and showed that none of them was predictive of PFS in adult FL patients (P>0.05). However, the variation in SUVmax (∆SUVmax) was predictive of PFS in adult FL patients (AUC=0.83, P=0.040), and the cutoff threshold was 4.85. I-PET using the D-5PS criteria cannot predict the PFS of adult FL patients treated with R-CHOP. However, the ∆SUVmax between B-PET and I-PET is applicable for the prognosis of adult patients with FL.

目的 探讨PSMA靶向分子探针 68Ga-THP-PSMA的制备,并初步评价该探针在诊断国内前列腺癌患者术后复发和转移中的价值.资料与方法 采用THP-PSMA药盒室温一步法制备 68Ga-THP-PSMA标记物,经0.22 μm无菌微孔滤膜过滤除菌,测定标记物细菌内毒素、放化纯和体外稳定性;前瞻性纳入2019年11月—2020年 3月上海交通大学医学院附属第一人民医院前列腺癌患者10例,静脉注射 68Ga-THP-PSMA后行1 h常规全身PET/CT显像和2 h延迟PET/CT显像,比较常规显像和延迟显像病灶的最大标准化摄取值(SUVmax),分析 68Ga-THP-PSMA阳性率与前列腺特异性抗原水平的关系.结果 THP-PSMA与 68GaCl3室温混合5 min后,标记率>95%[(98.74±1.06)%,n=10],在室温PBS体系和 37℃血清中具有良好的体外稳定性.10例前列腺癌患者的PET/CT显像显示,68Ga-THP-PSMA在肾脏和膀胱分布最高,其次为肝脏、脾脏和小肠,提示显像剂主要通过泌尿系统排泄;唾液腺、泪腺有较多生理性摄取;4 例患者共21个病灶具有明显摄取,判定为局部复发或转移灶;病灶的SUVmax值在1 h和2 h显像差异无统计学意义(12.74±1.68比13.44±1.67,t=0.59,P=0.28);经 68Ga-THP-PSMA判定为PET/CT显像阳性患者的前列腺特异性抗原水平显著高于 PET/CT 阴性患者(t=0.81,P=0.04).结论 68Ga-THP-PSMA 制备简单、快速、标记率稳定,可浓聚于前列腺癌病灶,信噪比高,对诊断前列腺癌术后复发或转移具有临床潜力.

PurposeCompared with PET/CT or PET/MRI, SPECT/CT is cheaper and more readily accessible. This study was designed to investigate the efficacy of 99mTc-HYNIC-PSMA SPECT/CT in detecting primary tumors and metastases in patients with newly diagnosed prostate cancer (PCa).MethodsA retrospective analysis of 31 patients with pathologically proven PCa was performed at Shanghai General Hospital from November 2020 to November 2021. Planar whole-body imaging was performed on all patients with a SPECT/CT scan of PSMA-positive regions 3–4 h after intravenous injection of 740 MBq 99mTc-HYNIC-PSMA. Positive PSMA uptake lesions were evaluated, and SUVmean and SUVmax were measured in each lesion. Associations between SPECT/CT parameters and clinicopathologic factors (tPSA and Gleason Score) were analyzed. The diagnostic capability of SPECT/CT parameters, tPSA, and GS in distant metastatic detection was evaluated by logistic regression.ResultsThe SUVmean and SUVmax of the high-risk stratification subgroups (tPSA>20 ng/ml, GS ≥8, and tPSA >20 ng/ml and GS≥8) were higher than those of the low-moderate risk stratification subgroups, with sensitivities of 92% and 92%, respectively. Neither SPECT/CT parameters (SUVmean, SUVmax) nor clinicopathologic factors (tPSA, GS) had high sensitivity (80%, 90%, 80%, and 90%, respectively, P <0.05) in distant metastatic prediction. For both the guideline tPSA level (20 ng/ml) and the cut-off level (84.3 ng/ml), the difference in the distant metastasis detection rate between the low predicted tPSA group and the high predicted tPSA group was statistically significant (0% vs. 47.62%, P = 0.005; 9.09% vs. 88.89%, P = 0.000, respectively). Twenty patients with pathological 99mTc-PSMA avid only in the prostate beds underwent radical prostatectomy. Seven of them underwent lymph node dissection, a total of 35 lymph nodes were removed, and no lymph nodes were detected with metastasis, which was consistent with 99mTc-HYNIC-PSMA SPECT/CT.Conclusion99mTc-HYNIC-PSMA SPECT/CT is effective in the risk stratification and distant metastasis detection of primary PCa patients. It is of great value in guiding treatment strategies.

Purpose:The unique structure of nanobodies is advantageous for the development of radiopharmaceuticals for nuclear medicine. Nanobodies targeted to human epidermal growth factor receptor 2 (HER2) can be used as tools for the imaging and therapy of HER2-overexpressing tumors. In this study, we aimed to describe the generation of a 131I-labeled anti-HER2 nanobody as a targeted radionuclide therapy (TRNT) agent for HER2-positive breast cancer.Methods:The anti-HER2 nanobody NM-02 was labeled with 131I using the iodogen method, and its radiochemical purity and stability in vitro were assessed. The pharmacokinetic profile of 131I-NM-02 was investigated in normal mice. Tumor accumulation, biodistribution, and therapeutic potential of 131I-NM-02 were evaluated in HER2-positive SKBR3 xenografts; HER2-negative MB-MDA-231 xenografts were used as the control group.Results:131I-NM-02 could be readily prepared with satisfactory radiochemical purity and stability in vitro. Apparent tumor uptake was observed in HER2-positive tumor-bearing mice with rapid blood clearance and favorable biodistribution. 131I-NM-02 could significantly inhibit tumor growth and extend the life of these mice with good organ compatibility. Negligible tumor accumulation and inhibitory effects of 131I-NM-02 were observed in the negative control group.Conclusion:131I-NM-02 has the potential to be explored as a novel tool for TRNT of HER2-positive breast cancer.

Objective:To explore the value of SPECT/CT imaging on programmed death receptor 1 ligand (PD-L1) expression in patients with non-small cell lung cancer (NSCLC) based on 99Tc m labeled anti-PD-L1 nanoantibodies (NM-01). Methods:From January 2019 to March 2020, a total of 14 patients (11 males, 3 females; age: (61.9±11.0) years) with pathologically confirmed NSCLC in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine were prospectively enrolled. NM-01 were labeled with 99Tc m, and patients were recruited for SPECT/CT imaging 2 h after injection with 99Tc m-NM-01((359.1±68.0) MBq). The differences of SUV max in primary and metastatic lesions between PD-L1 positive and negative patients were compared by independent sample t test. The correlation between the SUV max and PD-L1 expression of primary lesions was analyzed by Pearson correlation analysis. Results:Of 14 patients, 6 were PD-L1 positive and 8 were PD-L1 negative. 99Tc m-NM-01 showed obviously increased uptake in kidneys and liver, while mildly increased uptake in spleen and bone marrow. The SUV max of primary lesions was 4.69±1.88 and the SUV max of metastatic lesions was 2.04±1.32. The SUV max of primary lesions in PD-L1 positive patients was significantly higher than that of PD-L1 negative patients (5.99±1.99 vs 3.72±1.10; t=5.98, P=0.039). There was no significant difference in the SUV max of metastatic lesions between PD-L1 positive and negative patients (1.66±1.03 vs 2.35±1.46; t=-1.77, P=0.084). The SUV max of primary lesions was positively correlated with PD-L1 expression ( r=0.648, P=0.042). Conclusion:99Tc m-NM-01 can demonstrate the expression of PD-L1 in primary and metastatic lesions in NSCLC.