We aimed to explore the diagnostic value of [18F]F-NOTA-FAPI-FUSCC-07 ([18F]F-NOTA-FAPI) PET/CT in suspected recurrence ovarian cancer with CA125 dynamic rising but negative conventional imaging findings. Forty-one suspected recurrent ovarian cancers who experienced [18F]F-NOTA-FAPI PET/CT for further diagnosis because of continuously rising CA125 value but negative conventional imaging (CT, MR or [18F]FDG PET/CT) findings were enrolled from June 2022 to January 2024. All conventional and [18F]F-FAPI PET/CT scans were performed in sequence within one week. Clinical characteristics, treatment data, [18F]F-NOTA-FAPI PET/CT findings, and survival outcomes were recorded. Differences in [18F]F-NOTA-FAPI PET/CT parameters across CA125 levels were analyzed using the Mann-Whitney U test. [18F]F-NOTA-FAPI PET/CT was positive in 34 patients (82.93

Human epidermal growth factor receptor 2 (HER2) is overexpressed in various malignancies, making it an attractive target for radiotheranostics. Nanobodies offer an ideal platform for radiopharmaceutical development. Here, we reported a novel HER2-specific nanobody (NB46) engineered with a C-terminal glycine-serine-cysteine (GSC) tripeptide for site-specific NOTA conjugation and radiolabeling with 68Ga and 177Lu. [68Ga]Ga/[177Lu]Lu-NOTA-NB46 exhibited high HER2 affinity and specificity in vitro. In HER2-positive tumor-bearing mice, the radiotheranostic agents showed rapid blood clearance, favorable biodistribution, high tumor accumulation, and low nontarget uptake. [177Lu]Lu-NOTA-NB46 demonstrated prolonged tumor retention. Single-dose therapy with [177Lu]Lu-NOTA-NB46 significantly inhibited tumor growth and extended survival in a dose-dependent manner with good tolerability. The kidneys were the primary dose-limiting organ. [68Ga]Ga/[177Lu]Lu-NOTA-NB46 represents a promising radiotheranostic pair for HER2-positive tumors, supporting its further translation into clinical investigation.

This study aimed to evaluate 68Ga-NOTA-GSI PET/CT probe targeting granzyme B in assessing immune response and predicting progression‑free survival (PFS) in patients with non‑small cell lung cancer (NSCLC). In this prospective single-center trial (ChiCTR2200062089), 41 stage IIIB/IV non-small lung cancer patients underwent 68Ga-NOTA-GSI PET/CT after 2 treatment cycles. Mann-Whitney U test and Fisher’s exact test were used to analyze clinical and imaging characteristics of enrolled NSCLC patients. The performance of PET/CT parameters in evaluating immune response and 1-/2-year PFS was assessed using receiver operating characteristic (ROC) curves. Treatment response was evaluated by RECIST 1.1 after 4–6 cycles. ROC analysis, binary logistic regression, Kaplan-Meier survival analysis, and multivariable Cox regression were used to assess predictive performance, and a nomogram was constructed to predict 2-year PFS. Responders (n = 29) showed significantly higher SUVmax, SUVmean, and TBR than non-responders (n = 12) (all P < 0.05). SUVmax was an independent predictor of immune response (OR 15.6, 95

To evaluate the diagnostic efficacy of a novel FAP-targeted tracer, [¹⁸F]F-FAPI-FUSCC-07, for solitary pulmonary nodules (SPNs) and to develop a reliable prediction model by integrating PET functional parameters with CT morphological features. One hundred and thirty-seven patients with SPNs who underwent both [¹⁸F]F-FAPI-FUSCC-07 and [¹⁸F]F-FDG PET/CT were retrospectively enrolled in this study. Diagnostic performance of semi-quantitative parameters (SUVmax and TBR) for both tracers was evaluated and compared using ROC analysis. A multivariate logistic regression model was constructed in a training cohort (n = 100) and validated in an independent cohort (n = 37). Both [¹⁸F]F-FAPI-FUSCC-07 and [¹⁸F]F-FDG PET/CT were able to discriminate between benign and malignant SPNs effectively. Compared with [¹⁸F]F-FDG PET/CT, [¹⁸F]F-FAPI-FUSCC-07 PET/CT demonstrated significantly higher diagnostic accuracy (AUC for TBR of both tracers: 0.801 vs. 0.677, p < 0.05). To better leverage the advantages of [¹⁸F]F-FAPI-FUSCC-07 PET/CT, a diagnostic model combining FAPI uptake and CT morphological features was constructed using logistic regression. The model was formulated as P = 1 / (1 + e^(-x)), where P represents the probability of malignancy, x = -1.223 + 0.502 × TBRFAPI + 1.959 × lobulation. The diagnostic model achieved superior performance with an AUC of 0.866. In the validation set, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the model were 87.50

To evaluate lesion detection patterns and the risk-stratification value of paired 68Ga-PSMA-11 and 18F-FDG PET/CT in patients with post-prostatectomy biochemical recurrence (BCR) and negative conventional imaging, and to explore the hypothesis-generating biological context of dual-tracer phenotypes using public single-cell transcriptomic data. This retrospective single-center study included patients with post-prostatectomy BCR who underwent paired 68Ga-PSMA-11 and 18F-FDG PET/CT within 14 days and had negative conventional imaging within 1 month before PET/CT. Overall dual-tracer PET positivity was defined as at least 1 positive lesion on either tracer. Among patients with PET-detectable disease on either tracer, phenotypes were classified as PSMA+/FDG−, PSMA+/FDG+, or PSMA−/FDG+. Public single-cell RNA sequencing data were analyzed to assess the relationship between FOLH1 expression and glycolytic activity. Among 58 included patients, 21 (36.2

Claudin 18.2 (CLDN18.2)-positive tumor epithelial compartments and fibroblast activation protein (FAP)-positive stroma enriched in cancer-associated fibroblasts (CAFs) often exhibit complementary spatiotemporal heterogeneity, which may lead to unstable lesion detection or insufficient contrast when using single-target molecular imaging. We aimed to develop a FAP/CLDN18.2 dual-target probe, [68Ga]Ga-DOTA-FZ2R, and to evaluate imaging performance in comparison with single-target probes. A dual-target radiotracer, [68Ga]Ga-DOTA-FZ2R, targeting CLDN18.2 and FAP, was designed and synthesized. Its targeting ability and specificity were evaluated in CLDN18.2-positive and FAP-positive cells and tumor models (n = 3 per group or time point). Small-animal positron emission tomography/computed tomography (PET/CT) was performed in single-positive and dual-positive models with comparison against the corresponding single-target tracers. CLDN18.2 and FAP expression were also analyzed in a cohort of 34 patients with stage III poorly differentiated gastric cancer to assess their correlation and explore potential prognostic associations. [68Ga]Ga-DOTA-FZ2R showed high radiochemical purity, good stability, and strong affinity for both targets. In single-positive models, it achieved higher tumor uptake, longer tumor retention, and higher tumor-to-muscle and tumor-to-liver ratios than the corresponding monomeric tracers; notably, tumor uptake was more than 4-fold higher than that of [68Ga]Ga-FAPI-04. In dual-positive models (KPC1199CLDN18.2 and NUGC4CLDN18.2), the observed tumor uptake exceeded the predefined additive reference calculated from the two single-target tracers under the study conditions. Moreover, in the patient cohort, CLDN18.2 and FAP expression were independent (R2 = 0.002, P = 0.79), and combined assessment provided hypothesis-generating observations regarding potential prognostic stratification. [68Ga]Ga-DOTA-FZ2R may enable simultaneous targeting of tumor epithelial and stromal compartments and may improve imaging performance in preclinical models with complementary CLDN18.2/FAP heterogeneity. These findings support the feasibility of a dual-target PET imaging strategy for gastric cancer and warrant further clinical PET/CT validation.

To evaluate the diagnostic performance, quantitative characteristics, and clinical implications of Glucagon-Like Peptide-1 Receptor (GLP-1R) PET using 68Ga-exendin-4 in patients with indolent and aggressive insulinomas, and to refine its role in comprehensive disease assessment. In this prospective study, patients presenting with hypoglycemia and fulfilling Whipple’s triad were enrolled. All patients underwent 68Ga-exendin-4 PET/CT, and a subset also received 68Ga-DOTANOC PET/CT. The pathology of surgery and biopsy served as the reference standard. Patients were stratified into indolent and aggressive insulinoma groups. Diagnostic performance metrics were calculated, and logistic regression analysis was performed to identify predictors of hypoglycemia control. Ninety-six patients with suspected insulinoma were enrolled in this study (64 indolent, 25 aggressive insulinomas, and 7 non-insulinomas). For indolent insulinomas, 68Ga-exendin-4 PET/CT demonstrated a sensitivity of 98.4

Nectin-4 is markedly overexpressed in urothelial carcinoma (UC) and represents a promising theranostic target for both radiotherapy and positron emission tomography (PET) imaging. The Food and Drug Administration (FDA)-approved Nectin-4-targeted drug, enfortumab vedotin, has demonstrated substantial efficacy in the treatment of UC. Developing a non-invasive quantitative detection technology based on positron emission tomography/computed tomography (PET/CT) imaging is crucial for accurately measuring Nectin-4 expression levels, facilitating precise patient selection, treatment stratification, and efficacy monitoring in UC. In the present study, a series of 68Ga/177Lu-labelled covalent bicyclic peptide (68Ga/177Lu-FZ-NRs) targeted Nectin-4 were constructed for PET/CT imaging and targeted radiotherapy based on a SuFEx-bio-orthogonal strategy. In vitro experiments demonstrated that 68Ga/177Lu-FZ-NRs exhibited high radiochemical purity, stability, and strong Nectin-4 affinity. MicroPET/CT imaging confirmed that covalent 68Ga-FZ-NRs exhibited strong tumor enrichment, low off-target binding, and excellent tumor/muscle ratios (> 4.90 at 60 min), thus validating Nectin-4 as an effective imaging target. In terms of clinical translation, all the 68Ga-FZ-NRs localized in a highly precise manner to lesions in UC patients. PET/CT-positive areas matched 18F-Fluorodeoxyglucose (18F-FDG) positioning and regions of high Nectin-4 expression in biopsied tissues. In terms of radiotherapy, covalent 177Lu-FZ-NRs exhibited a significantly higher tumor uptake (an average increase of 4-fold at 24 h) and retention ( 4-fold longer, up to 48 h) than non-covalent 177Lu-FZ-NR-1, thus enhancing therapeutic effects. In treatment experiments, covalent 177Lu-FZ-NRs strongly inhibited tumor growth without obvious toxicity. In summary, our novel Nectin-4-targeted covalent bicyclic peptide radioligands provide new molecular imaging tools for the non-invasive assessment of Nectin-4 and establish a foundation for UC-targeted radiotherapy.

[99mTc]Tc-HYNIC-PSMA-XL-2 is a PSMA-targeted SPECT tracer with low urinary bladder activity. We assessed its real-world performance in paired head-to-head comparisons versus [99mTc]Tc-MDP and PSMA PET/CT. Single-center retrospective study (Jan 1, 2020–Nov 25, 2025) using within-patient paired scans within 30 days. Subcohort A included [99mTc]Tc-HYNIC-PSMA-XL-2 SPECT/CT vs. [99mTc]Tc-MDP (n = 38). Subcohort B included [99mTc]Tc-HYNIC-PSMA-XL-2 SPECT/CT vs. PSMA PET/CT (either [68Ga]Ga-PSMA-11 or [18F]PSMA-1007; n = 13). Lesions were classified by a composite reference standard (Gold+/Gold−). Sensitivity/specificity/accuracy were compared with McNemar’s test; non-inferiority versus PET/CT used Δ = 10

Ephrin type-A receptor 2 (EphA2) is a promising target in pancreatic ductal adenocarcinoma (PDAC). However, the clinical potential of targeting EphA2 requires further imaging evaluation. This study developed and preliminarily evaluated a novel 68Ga-labeled radiotracer for PET imaging of EphA2 expression in PDAC patients. 68Ga-FZEAR-1, 68Ga-FZEAR-2, and 68Ga-FZEAR-3 were synthesized, and their stability, affinity, pharmacokinetics were evaluated in vitro and in vivo. Further biological evaluation was performed in EphA2-positive and EphA2-negative tumor xenografts. A pilot first-in-human PET/CT study of the lead candidate, 68Ga-FZEAR-2, was subsequently conducted in two PDAC patients. The three 68Ga-radiotracers were synthesized with high radiochemical purity (> 99

Triple-negative breast cancer (TNBC) features pronounced molecular heterogeneity and poor prognosis, restricting the efficacy of single-targeted strategies. Leveraging the complementary theranostic targets fibroblast activation protein (FAP) and Nectin-4, we designed the novel hetero-bivalent agent FZ-NF-1 for dual targeting. Preclinically, both 68Ga-labeled and 177Lu-labeled FZ-NF-1 exhibited high radiochemical purity, good stability, and high affinity for both Nectin-4 and FAP. 68Ga-FZ-NF-1 revealed better tumor uptake and prolonged retention time compared to monomeric FAP- or Nectin-4 targeted tracers. Moreover, 177Lu-FZ-NF-1 exhibited sustained tumor accumulation for upto 120 h post-injection, leading to significant, dose-dependent tumor regression in TNBC mouse models, with no obvious systemic toxicity observed. In a preliminary first-in-human translational study involving 13 patients with TNBC, 68Ga-FZ-NF-1 demonstrated comparable tumor uptake to that of 18F-fluorodeoxyglucose (18F-FDG), while successfully identifying additional lesions missed by 18F-FDG. Complementary tissue microarray analysis of 60 TNBC cases confirmed the heterogeneous expression of Nectin-4 and FAP in TNBC. By concurrently targeting the tumor cells and stroma, 68Ga/177Lu-FZ-NF-1 effectively mitigates the limitations associated with single-target imaging and therapy. These results indicate that the heterodimeric theranostic pair offers enhanced imaging performance and significant therapeutic efficacy, providing a promising strategy for the personalized management of refractory TNBC.

Carbonic anhydrase IX (CAIX) represents a promising target for molecular imaging of clear cell renal cell carcinoma (ccRCC). We designed three radiotracers targeting CAIX to improve the diagnostic value of imaging by increasing tumor uptake and the liver excretion pathway. We also aimed to demonstrate the feasibility of applying small-molecule radiotracers in VEGFR-TKI efficacy monitoring in renal cancer. This study developed three novel CAIX-targeting radiotracers, which were evaluated in vitro and in vivo; The study also included 8 patients with ccRCC, all of whom had paired [68Ga]Ga-NOTA-FZCI-3 PET/CT and [18F]-FDG PET/CT. The diagnostic efficacies of these two PET tracers were compared. Moreover, VEGFR-TKI efficacy monitoring experiments using [68Ga]Ga-NOTA-FZCI-3 was conducted on OS-RC-2 models. Three radiotracers showed that different liver/renal accumulations were better correlated with factors including distinct plasma protein binding abilities. [68Ga]Ga-NOTA-FZCI-3, primarily cleared through the hepatobiliary system in patients, demonstrated a higher SUVmax of renal lesions (median, 13.10 vs. 3.10, n = 4; *P = 0.04) and superior tumor-to-muscle ratio of metastatic lesions (9.25 ± 5.10 vs.3.64 ± 2.11, n = 16; **P = 0.004) to [18F]-FDG in a prospective cohort with 8 ccRCC patients. In VEGFR-TKI efficacy monitoring experiments, [68Ga]Ga-NOTA-FZCI-3 showed markedly decreased tumor radiotracer uptake throughout treatment. Moreover, VEGFR-AKT-mTOR pathway inhibition and CAIX downregulation in the treatment group confirmed that [68Ga]Ga-NOTA-FZCI-3 PET/CT is a viable strategy for monitoring TKI efficacy in renal cell cancer. [68Ga]Ga-NOTA-FZCI-3 is a promising radiotracer for improving diagnosis, staging, and VEGFR-TKI efficacy monitoring in ccRCC.

Prognostic stratification for microsatellite stable (MSS) gastric cancer (GC) remains challenging. This study evaluated the predictive and prognostic value of [68Ga]Ga-NOTA-GSI PET/CT imaging in a large cohort of MSS GC patients receiving chemo-immunotherapy. In this retrospective study, 145 patients with MSS GC underwent [68Ga]Ga-NOTA-GSI PET/CT after two or three cycles of chemo-immunotherapy. Measurements included SUVmax, SUVmean, GSI tumor volume (GSI-TV), total lesion uptake (TLU), tumor-liver ratio (TLR), and tumor-blood ratio (TBR). The study analyzed associations between short-term treatment response (RECIST 1.1 or tumor regression grade score) and progression-free survival (PFS) using receiver operating characteristic (ROC) curves, logistic regression, and Cox proportional hazards models. Responders exhibited significantly higher uptake of [68Ga]Ga-NOTA-GSI than non-responders, including SUVmax, sumSUVmax, and TBR (all P < 0.05) across all patients and various subgroups, while volumetric parameters (GSI-TV, TLU) showed no notable difference. SUVmax was a reliable predictor of response (AUC = 0.755 for all patients; AUC = 0.882 for the neoadjuvant subgroup). In survival analysis, an SUVmax ≥ 2.6 independently predicted significantly longer PFS (median PFS of 14.0 vs. 9.0 months; hazard ratio, 0.673; P = 0.016). The study highlighted the significant value of [68Ga]Ga-NOTA-GSI PET/CT in assessing the effectiveness of chemo-immunotherapy and predicting outcomes in MSS gastric cancer patients. Subgroup analysis confirmed its reliable predictive power across neoadjuvant, palliative, and adjuvant treatments, supporting the potential for its broad clinical application.

Nectin-4 is a promising theranostic target for cancers treatment due to its high abundance/expression in different cancer entities such as bladder cancer, breast cancer, and pancreatic cancer This study evaluated the biodistribution and radiation dosimetry of [⁶⁸Ga]Ga-DOTA-Sar¹⁰-Nectin-4 ([⁶⁸Ga]Ga-FZ-NR-1), a novel Nectin-4-targeting PET tracer developed by our team, to assess its safety and support its clinical translation. Eight patients with pathologically confirmed malignancies (breast cancer, pancreatic cancer, or bladder cancer) underwent whole-body (WB) PET/CT scans at 10, 40, and 180 min after the injection of [⁶⁸Ga]Ga-FZ-NR-1. The images were reconstructed using the Ordered Subset Expectation Maximization (OSEM) algorithm with TOF and PSF technology. The brain, salivary, heart, lungs, stomach, spleen, liver, gallbladder, pancreas, kidneys, colon, and prostate in males or uterus in females as target organs were semi-automatically segmented on PET/CT images using the Hermes Internal Radiation Dosimetry (HIRD) software toolkit. Time-activity curves (TACs) were obtained for these organs based on measured activity concentrations. The time-integrated activity coefficients (TIACs) of these target organs were calculated by integrating the TACs. Organ-specific absorbed doses and the total body effective dose were estimated using IDAC-Dose 2.1 software. Meanwhile, bladder dosimetry employed a standard voiding model. [⁶⁸Ga]Ga-FZ-NR-1 was cleared rapidly, primarily via the urinary system. The highest organ absorbed doses per injected activity unit were observed in the kidneys (2.24 × 10⁻¹ mGy/MBq) and bladder wall (1.24 × 10⁻¹ mGy/MBq). Other notable organs were the salivary glands, with an absorbed dose of approximately 2.54 × 10⁻² mGy/MBq. The estimated total body effective dose per injected activity unit was approximately 2.00 × 10⁻² mSv/MBq. Preliminary clinical imaging showed high tracer uptake in breast, pancreatic, and bladder cancer lesions, highlighting its promising diagnostic potential for detecting Nectin-4-expressing tumors. This human dosimetry assessment of [⁶⁸Ga]Ga-FZ-NR-1 showed a total body effective dose of approximately 2.00 × 10⁻² mSv/MBq, similar to other 68Gallium-labeled tracers. Organ absorbed doses were well within the accepted limits, suggesting a favorable radiation risk profile for clinical application as a PET imaging agent targeting Nectin-4. Initial clinical imaging results demonstrates that [⁶⁸Ga]Ga-FZ-NR-1 provides clear visualization of both primary tumors and metastases with high Nectin-4 expression levels.

To improve the detection of neuroendocrine neoplasms (NENs), we developed a series of octreotide-based somatostatin receptor (SSTR)-targeted probes and sought to identify an optimal candidate through preclinical and clinical head-to-head evaluation versus [68Ga]Ga-DOTA-TATE and [68Ga]Ga-DOTA-NOC. Eight original probes were synthesised and radiolabelled with 68Ga or 18F. The in vitro stability of the probes in saline and human serum, as well as their in vivo stability through urine sampling, was determined by radio-high-performance liquid chromatography (radio-HPLC). Micro-PET/CT imaging was performed in AR42J xenograft-bearing mice 60 min after injection of the radiotracers via the tail vein. On the basis of preclinical screening, [18F]AlF-NOTA-FZSR was selected for clinical PET/CT and directly compared with [68Ga]Ga-DOTA-TATE and [68Ga]Ga-DOTA-NOC in patients with NENs. All probes were successfully synthesised and radiolabelled with high radiochemical purity (> 98

Tyrosine protein kinase c-Met, encoded by the Met gene, is a membrane-associated receptor tyrosine kinase that is often aberrantly expressed in a wide range of tumors. The development of imaging probes specifically targeting c-Met is critical for improving cancer diagnostics. In this study, we successfully designed and fabricated an aptamer molecular imaging probe ([68Ga]Ga-NOTA-SL1) with high radiochemical purity (RCP), good stability in vitro, and high affinity for c-Met expressed tumors. As shown by the micro-PET/CT scanning, [68Ga]Ga-NOTA-SL1 efficiently imaged tumor models with varying c-Met expression. The quantitative analysis of micro-PET/CT showed tumor uptake of [68Ga]Ga-NOTA-SL1 in the HCC827 tumor models (30 min, 2.93 ± 0.64%ID/g; 60 min, 2.03 ± 0.67%ID/g; 90 min, 1.63 ± 0.61%ID/g), PC-9 tumor models (30 min, 2.1 ± 0.72%ID/g; 60 min, 1.7 ± 0.56%ID/g; 90 min, 1.33 ± 0.38%ID/g), and HCT116 tumor models (30 min, 1.4 ± 0.17%ID/g; 60 min, 1.23 ± 0.15%ID/g; 90 min, 0.97 ± 0.21%ID/g). The results of immunohistochemistry (IHC) further confirmed the targeting ability of [68Ga]Ga-NOTA-SL1 to c-Met from a molecular pathological perspective. The probe effectively imaged c-Met-positive tumors and demonstrated a favorable metabolism profile and targeting performance in non-small cell lung cancer (NSCLC) or colorectal cancer tumor models. Consequently, this probe shows promise as an imaging agent capable of providing valuable diagnostic insights into tumors with aberrant c-Met expression.

BACKGROUND:We aimed to investigate potential biomarkers for predicting pathological complete response (pCR) to neoadjuvant therapy in HER2-positive breast cancer, with a focus on early-stage indicators. METHODS:We conducted a comprehensive analysis incorporating genomic and PET imaging data from 61 patients undergoing neoadjuvant treatment. Genomic profiling and PET/CT scans were performed at baseline (T1) and after one treatment cycle (T2). Various clinical and molecular parameters were assessed, including HER2 gene status, maximum standardized uptake value, and genomic alterations. RESULTS:Our findings revealed several candidate biomarkers associated with treatment response. Early changes in 18 F-FDG PET/CT and baseline 68 Ga-HER2 PET/CT emerged as potential predictors for pCR. Genomic analysis identified differences in mutation frequencies, with notable changes after one treatment cycle. A multivariate predictive model, incorporating PET imaging and clinical characteristics, demonstrated excellent performance in forecasting treatment response. CONCLUSIONS:The study underscores the significance of early biomarkers in predicting neoadjuvant treatment outcomes for HER2-positive breast cancer. Integrating genomic and imaging data provides a comprehensive approach for tailoring therapeutic strategies. The identified biomarkers hold promise for guiding treatment escalation or de-escalation, presenting a step forward in personalized management for HER2-positive breast cancer patients.

Purpose:None of the antibody-drug conjugates (ADCs) targeting Claudin 18.2 (CLDN18.2) have received approval from regulatory authorities due to their limited clinical benefits. Leveraging the radiosensitizing ability of Deruxtecan (DXd) and the internal radiation therapy of 131I for tumors, we aimed to develop the first radio-antibody-drug conjugates (RADCs) for the treatment of gastric cancer. Methods:The CLDN18.2-specific antibody HLX58 was conjugated with the payload DXd through a cleavable maleimide glycynglycyn-phenylalanyn-glycyn (GGFG) peptide linker. HLX58-Der was labeled with 131I to produce RADC-131I-HLX58-Der. HLX58 was labeled with 125I for imaging CLDN18.2-positive tumors, providing a reference for RADC treatment in solid tumors. The antigen-binding properties and biodistribution of the RADC were studied both in vitro and in vivo. The cytotoxic effects of the RADC were evaluated in CLDN18.2-positive tumor cell lines and xenografts. Results:HLX58 was successfully conjugated with DXd using the cleavable maleimide GGFG peptide linker and labeled with 131I to produce RADC-131I-HLX58-Der. HLX58 was labeled with 125I for imaging CLDN18.2-positive tumors. Both 125I-HLX58 and 131I-HLX58-Der exhibited significant binding affinity for the CLDN18.2-positive cancer cell line. The cytotoxic effect of 131I-HLX58-Der was observed in the CLDN18.2-positive cell line, with an IC50 of 11.28 ng/mL. In terms of cytotoxicity, 131I-HLX58-Der exhibited greater activity compared to HLX58-Der. 125I-HLX58 and 131I-HLX58-Der demonstrated similar biodistribution profiles in CLDN18.2-positive tumor models, achieving 5.72 ± 0.41%ID/g (48 h) and 5.83 ± 0.41%ID/g (72 h) in the tumor tissues postinjection, respectively. The average tumor size in groups treated with 131I-HLX58-Der and HLX58-Der was reduced by factors of 12.15 and 4.80, respectively, compared to the control group. 131I-HLX58-Der demonstrated no toxic effects on hepatorenal function, routine blood tests, or major organs in mice when compared to the control group. Conclusion:These findings validate the potential of RADCs targeting CLDN18.2 in treating CLDN18.2-expressing solid tumors.

Accurate and real-time evaluation of tumor ER and HER2 status is essential for improving the clinical management of patients with metastatic breast cancer (MBC). The purpose of this pilot study was to investigate the value of PET imaging with 18F-FES and 68 Ga-HER2 affibody for the noninvasive evaluation of the ER and HER2 status in MBC patients. From January 2021 to September 2023, 17 metastatic breast cancer (MBC) patients underwent 1⁸F-FES and ⁶⁸Ga-HER2-affibody PET/CT within one month, with concurrent 1⁸F-FDG PET/CT for tumor glycolytic activity evaluation. The imaging data were integrated to detect lesions and analyze intra-patient heterogeneity. The efficacy of lesion detection across different modalities was evaluated, along with an assessment of their potential impact on clinical decision-making. A total of 174 metastatic lesions were detected: 163 (93.7