The high incidence and heavy disease burden of prostate cancer (PC) require accurate and comprehensive assessment for appropriate disease management. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) cannot detect PSMA-negative lesions, despite its key role in PC disease management. The overexpression of gastrin-releasing peptide receptor (GRPR) in PC lesions reportedly performs as a complementary target for the diagnosis and therapy of PC. Radiopharmaceuticals derived from the natural ligands of GRPR have been developed. These radiopharmaceuticals enable the visualization and quantification of GRPR within the body, which can be used for disease assessment and therapeutic guidance. Recently developed radiopharmaceuticals exhibit improved pharmacokinetic parameters without deterioration in affinity. Several heterodimers targeting GRPR have been constructed as alternatives because of their potential to detect tumor lesions with a low diagnostic efficiency of single target detection. Moreover, some GRPR-targeted radiopharmaceuticals have entered clinical trials for the initial staging or biochemical recurrence detection of PC to guide disease stratification and therapy, indicating considerable potential in PC disease management. Herein, we comprehensively summarize the progress of radiopharmaceuticals targeting GRPR. In particular, we discuss the impact of ligands, chelators, and linkers on the distribution of radiopharmaceuticals. Furthermore, we summarize a potential design scheme to facilitate the advancement of radiopharmaceuticals and, thus, prompt clinical translation.

BACKGROUND: Interlesional response heterogeneity (ILRH) poses challenges to the treatment of metastatic castration-resistant prostate cancer (mCRPC). Currently, there are no prospective clinical trials exploring the prognostic significance of ILRH on paired positron emission tomography/computed tomography (PET/CT) in the context of abiraterone therapy.
METHODS: In this prospective study, we enrolled patients with mCRPC treated with abiraterone (ClinicalTrials.gov: NCT05188911; ChiCTR.org.cn: ChiCTR2000034708). 68Ga-prostate-specific membrane antigen (PSMA)+18F-fluorodeoxyglucose (FDG) PET/CT and circulating tumor DNA (ctDNA) monitoring were performed at baseline and week 13. Patients were grouped by their early ILRH measurement. The primary endpoint was to evaluate the predictive role of ILRH for conventional progression-free survival (PFS) through the concordance index (C-index) assessment. Conventional PFS was defined as the time from medication to conventional radiographic progression, clinical progression, or death.
RESULTS: Ultimately, 33 patients were included with a median follow-up of 28.7 months. Baseline+week 13 PSMA PET/CT revealed that 33.3% of patients showed ILRH. Those patients with hetero-responding disease had significantly different PFS compared to the responding and non-responding groups (hazard ratio: responding group = reference, hetero-responding group = 4.0, non-responding group = 5.8; p < 0.0001). The C-index of ILRH on paired PSMA PET/CT (0.742 vs. 0.660) and FDG PET/CT (0.736 vs. 0.668) for conventional PFS was higher than that of PSA response. In an exploratory analysis, PSMA-/FDG+ lesions at week 13 were identified as a strong surrogate for poor conventional PFS (p = 0.039).
CONCLUSIONS: ILRH on both baseline+week 13 PSMA and FDG PET/CT strongly associated with conventional PFS.
BACKGROUND: This study was funded by the Ministry of Science and Technology of China and Shanghai.

BACKGROUND: To investigate the potential utility of quantitative parameters obtained by 18F-fibroblast activation protein inhibitor positron emission tomography/computed tomography ([18F]AlF-NOTA-FAPI-04 PET/CT) in the assessment of organ involvement and disease activity in IgG4-related disease (IgG4-RD).
METHODS: This study enrolled patients who underwent [18F]AlF-NOTA-FAPI-04 PET/CT scans at the Department of Rheumatology, The First Affiliated Hospital, Zhejiang University School of Medicine from August 2021 to August 2022. The PET/CT images of the included patients were re-evaluated by PET center technicians, and the maximal standardized uptake value (SUVmax), metabolic lesion volume (MLV), and total lesion FAPI (TL-FAPI) were used to evaluate the involved organs and tissues that abnormally accumulated [18F]AlF-NOTA-FAPI-04. The clinical and laboratory data of patients are also systematically collected and analyzed.
RESULTS: Among the patients included in this study, 12 patients met the IgG4-RD classification criteria established by the American College of Rheumatology in 2019. Among them, 8 were males and 4 were females, with an average age of 59.3 ± 11.5 years. 50% of IgG4-RD patients were found with more organ involvement on PET/CT than physical examination, ultrasonography, and computed tomography. IgG4 levels (Rho = 0.594, p = 0.042) and IgG4-RI (Rho = 0.647, p = 0.023) were significantly positively correlated with TL-FAPI. After linear regression analysis, only TL-FAPI showed a predictive value of RI (R2 = 0.356, B = 0.008, p = 0.041).
CONCLUSIONS: [18F]AlF-NOTA-FAPI-04 PET/CT is a useful tool for identifying asymptomatic organ involvement and assessing disease activity. The TL-FAPI as an indicator was positively correlated with IgG4-RD disease activity.

UNASSIGNED: To explore the value of 18F-fluordeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) semi-quantitative parameters of primary tumor combined with squamous cell carcinoma antigen (SCC-Ag) in predicting lymph node metastasis (LNM) of cervical cancer (FIGO 2018 stage I-II).
UNASSIGNED: A total of 65 patients with stage I-II cervical cancer underwent 18F-FDG PET/CT were included in our study. Comparing the primary tumor 18F-FDG PET/CT semi-quantitative parameters and SCC-Ag between the LNM group and the non-LNM group. Logistic regression and receiver operating characteristic (ROC) were used to analyze the value of 18F-FDG PET/CT metabolic parameters and SCC-Ag in predicting LNM.
UNASSIGNED: There were 14 and 51 patients were classified as having LNM and NLNM. The semi-quantitative parameters, including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), the total lesion glycolysis (TLG), the metabolic tumor volume (MTV) of the tumor and SCC-Ag were all significantly higher in LNM than in NLNM (SUVmax, 16.07 ± 7.81 vs 11.19 ± 4.73, SUVmean, 9.16 ± 3.48 vs 6.29 ± 2.52, SUVpeak, 12.70 ± 5.26 vs 7.65 ± 3.26, MTV, 22.77 ± 12.36 vs 7.09 ± 5.21, TLG, 211.01 ± 154.25 vs 43.38 ± 36.17, SCC-Ag, 5.39 ± 4.56 vs 2.13 ± 2.50, all p<0.01). Logistic regression analysis showed that TLG was an independent predictor of LNM in stage I-II cervical cancer (OR 1.032, 95% CI 1.013-1.052, p<0.01). Moreover, the predictive value of TLG combined with SUVpeak and SCC-Ag increased and the area under the curve increased compared SUVpeak and SCC-Ag.
UNASSIGNED: 18F-FDG PET/CT semi-quantitative parameters and SCC-Ag have promise for assessing LNM in stage I-II cervical cancer. TLG of primary tumor provides independent and increasing values in predicting LNM in stage I-II cervical cancer.

BACKGROUND: Rising prostate-specific antigen (PSA) levels following radical prostatectomy are indicative of a poor prognosis, which may associate with periprostatic adipose tissue (PPAT). Accordingly, we aimed to construct a dynamic online nomogram to predict tumor short-term prognosis based on 18F-PSMA-1007 PET/CT of PPAT.
METHODS: Data from 268 prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT before prostatectomy were analyzed retrospectively for model construction and validation (training cohort: n = 156; internal validation cohort: n = 65; external validation cohort: n = 47). Radiomics features (RFs) from PET and CT were extracted. Then, the Rad-score was constructed using logistic regression analysis based on the 25 optimal RFs selected through maximal relevance and minimal redundancy, as well as the least absolute shrinkage and selection operator. A nomogram was constructed to predict short-term prognosis which determined by persistent PSA.
RESULTS: The Rad-score consisting of 25 RFs showed good discrimination for classifying persistent PSA in all cohorts (all P < 0.05). Based on the logistic analysis, the radiomics-clinical combined model, which contained the optimal RFs and the predictive clinical variables, demonstrated optimal performance at an AUC of 0.85 (95% CI: 0.78-0.91), 0.77 (95% CI: 0.62-0.91) and 0.84 (95% CI: 0.70-0.93) in the training, internal validation and external validation cohorts. In all cohorts, the calibration curve was well-calibrated. Analysis of decision curves revealed greater clinical utility for the radiomics-clinical combined nomogram.
CONCLUSIONS: The radiomics-clinical combined nomogram serves as a novel tool for preoperative individualized prediction of short-term prognosis among PCa patients.

BACKGROUND: Breast cancer is a serious threat to women\'s health with high morbidity and mortality. The development of more effective therapies for the treatment of breast cancer is strongly warranted. Growing evidence suggests that targeting glucose metabolism may be a promising cancer treatment strategy. We previously identified a new glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor, DC-5163, which shows great potential in inhibiting tumor growth. Here, we evaluated the anticancer potential of DC-5163 in breast cancer cells.
METHODS: The effects of DC-5163 on breast cancer cells were investigated in vitro and in vivo. Seahorse, glucose uptake, lactate production, and cellular ATP content assays were performed to examine the impact of DC-5163 on cellular glycolysis. Cell viability, colony-forming ability, cell cycle, and apoptosis were assessed by CCK8 assay, colony formation assay, flow cytometry, and immunoblotting respectively. The anticancer activity of DC-5163 in vivo was evaluated in a mouse breast cancer xenograft model.
RESULTS: DC-5163 suppressed aerobic glycolysis and reduced energy supply of breast cancer cells, thereby inhibiting breast cancer cell growth, inducing cell cycle arrest in the G0/G1 phase, and increasing apoptosis. The therapeutic efficacy was assessed using a breast cancer xenograft mouse model. DC-5163 treatment markedly suppressed tumor growth in vivo without inducing evident systemic toxicity. Micro-PET/CT scans revealed a notable reduction in tumor 18F-FDG and 18F-FLT uptake in the DC-5163 treatment group compared to the DMSO control group.
CONCLUSIONS: Our results suggest that DC-5163 is a promising GAPDH inhibitor for suppressing breast cancer growth without obvious side effects. 18F-FDG and 18F-FLT PET/CT can noninvasively assess the levels of glycolysis and proliferation in tumors following treatment with DC-5163.

BACKGROUND: The proposed trial is to examine the feasibility of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided cytoreduction plus apalutamide and androgen deprivation therapy (ADT) for newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) at oligometastatic state.
METHODS: CHAMPION (NCT05717582) is an open-label, single-arm, phase II trial, planning to enroll newly diagnosed mHSPC cases with oligometastases (≤ 10 distant metastatic sites in conventional imaging). Patients will receive 6 cycles of apalutamide plus ADT. Patients with oligometastatic disease at PSMA PET/CT after 3 treatment cycles will receive cytoreductive radical prostatectomy. PSMA PET/CT-guided metastasis-directed external radiation therapy will be determined by the investigators. Apalutamide plus ADT will be continued for 2 weeks postoperatively. The primary endpoint is the proportion of patients with undetectable prostate-specific antigen (PSA), no disease progression, and no symptom deterioration after 6 cycles of apalutamide plus ADT. Secondary endpoints include the percentage of patients with PSA ≤ 0.2 ng/mL and oligometastases by the end of 3 treatment cycles, PSA response rate, and safety. Fleming\'s two-stage group sequential design will be adopted in the study, where the null hypothesis is that the rate of patients with an undetectable PSA is ≤ 40% after 6 cycles of treatment, while the alternate hypothesis is an undetectable PSA of > 60%; with one-sided α = 0.05, power = 0.80, and an assumed dropout rate of 10%, the required number of patients for an effective analysis is 47. Enrolment in the study commenced in May 2023.
CONCLUSIONS: The multi-modal therapy based on treatment response may improve the prognosis of newly diagnosed mHSPC patients with oligometastases.
BACKGROUND: The study is registered with Clinical Trials.Gov (NCT05717582). Registered on 8th February 2023.

OBJECTIVE: To build a risk stratification by incorporating PET/CT-based deep learning features and whole-body metabolic tumor volume (MTVwb), which was to make predictions about overall survival (OS) and progression-free survival (PFS) for those with non-small cell lung cancer (NSCLC) as a complement to the TNM staging.
METHODS: The study enrolled 590 patients with NSCLC (413 for training and 177 for testing). Features were extracted by employing a convolutional neural network. The combined risk stratification (CRS) was constructed by the selected features and MTVwb, which were contrasted and integrated with TNM staging. In the testing set, those were verified.
RESULTS: Multivariate analysis revealed that CRS was an independent predictor of OS and PFS. C-indexes of the CRS demonstrated statistically significant increases in comparison to TNM staging, excepting predicting OS in the testing set (for OS, C-index=0.71 vs. 0.691 in the training set and 0.73 vs. 0.736 in the testing set; for PFS, C-index=0.702 vs. 0.686 in the training set and 0.732 vs. 0.71 in the testing set). The nomogram that combined CRS with TNM staging demonstrated the most superior model performance in the training and testing sets (C-index=0.741 and 0.771).
CONCLUSIONS: The addition of CRS improves TNM staging\'s predictive power and shows potential as a useful tool to support physicians in making treatment decisions.

OBJECTIVE: The value of preoperative multidisciplinary approach remains inadequately delineated in forecasting postoperative outcomes of patients undergoing coronary artery bypass grafting (CABG). Herein, we aimed to ascertain the efficacy of multi-modality cardiac imaging in predicting post-CABG cardiovascular outcomes.
METHODS: Patients with triple coronary artery disease underwent cardiac sodium [18F]fluoride ([18F]NaF) positron emission tomography/computed tomography (PET/CT), coronary angiography, and CT-based coronary artery calcium scoring before CABG. The maximum coronary [18F]NaF activity (target-to-blood ratio [TBR]max) and the global coronary [18F]NaF activity (TBRglobal) was determined. The primary endpoint was perioperative myocardial infarction (PMI) within 7-day post-CABG. Secondary endpoint included major adverse cardiac and cerebrovascular events (MACCEs) and recurrent angina.
RESULTS: This prospective observational study examined 101 patients for a median of 40 months (interquartile range: 19-47 months). Both TBRmax (odds ratio [OR] = 1.445; p = 0.011) and TBRglobal (OR = 1.797; P = 0.018) were significant predictors of PMI. TBRmax>3.0 (area under the curve [AUC], 0.65; sensitivity, 75.0%; specificity, 56.8%; p = 0.036) increased PMI risk by 3.661-fold, independent of external confounders. Kaplan-Meier test revealed a decrease in MACCE survival rate concomitant with an escalating TBRmax. TBRmax>3.6 (AUC, 0.70; sensitivity, 76.9%; specificity, 73.9%; p = 0.017) increased MACCEs risk by 5.520-fold. Both TBRmax (hazard ratio [HR], 1.298; p = 0.004) and TBRglobal (HR = 1.335; p = 0.011) were significantly correlated with recurrent angina. No significant associations were found between CAC and SYNTAX scores and between PMI occurrence and long-term MACCEs.
CONCLUSIONS: Quantification of coronary microcalcification activity via [18F]NaF PET displayed a strong ability to predict early and long-term post-CABG cardiovascular outcomes, thereby outperforming conventional metrics of coronary macrocalcification burden and stenosis severity.
BACKGROUND: The trial was registered with the Chinese Clinical Trial Committee (number: ChiCTR1900022527; URL: www.chictr.org.cn/showproj.html?proj=37933 ).

BACKGROUND: This study aimed to compare the diagnostic value of [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT imaging for primary lesions and metastatic lymph nodes in patients with tonsil cancer.
METHODS: Twenty-one tonsil cancer patients who underwent [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT scans within two weeks in our centre were retrospectively enrolled. The maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR) of the two tracers were compared by using the Mann‒Whitney U test. In addition, the sensitivity, specificity, and accuracy of the two methods for diagnosing metastatic lymph nodes were analysed.
RESULTS: In detecting primary lesions, the efficiency was higher for [68 Ga]Ga-DOTA-FAPI-04 PET/CT (20/22) than for [18F]FDG PET/CT (9/22). Although [68 Ga]Ga-DOTA-FAPI-04 uptake (SUVmax, 5.03 ± 4.06) was lower than [18F]FDG uptake (SUVmax, 7.90 ± 4.84, P = 0.006), [68 Ga]Ga-DOTA-FAPI-04 improved the distinction between the primary tumor and contralateral normal tonsillar tissue. The TBR was significantly higher for [68 Ga]Ga-DOTA-FAPI-04 PET/CT (3.19 ± 2.06) than for [18F]FDG PET/CT (1.89 ± 1.80) (p < 0.001). In lymph node analysis, SUVmax and TBR were not significantly different between [68 Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT (7.67 ± 5.88 vs. 8.36 ± 6.15, P = 0.498 and 5.56 ± 4.02 vs. 4.26 ± 3.16, P = 0.123, respectively). The specificity and accuracy of [68 Ga]Ga-DOTA-FAPI-04 PET/CT were higher than those of [18F]FDG PET/CT in diagnosing metastatic cervical lymph nodes (all P < 0.05).
CONCLUSIONS: The availability of [68 Ga]Ga-DOTA-FAPI-04 complements the diagnostic results of [18F]FDG by improving the detection rate of primary lesions and the diagnostic accuracy of cervical metastatic lymph nodes in tonsil cancer compared to [18F]FDG.