Prostate-specific membrane antigen (PSMA) is highly overexpressed in prostate cancer (PCa) and represents an attractive target for radiotheranostic applications. While conventional approaches often convert PSMA-targeted imaging agents into therapeutic counterparts through chelator substitution, we explored a dual-chelator strategy by integrating HBED-CC and DOTA into the PSMA-093 scaffold. This design generated three dual-chelator conjugates (1-3) capable of supporting the chelation of both diagnostic and therapeutic radionuclides within a single molecular platform. The compounds were successfully radiolabeled with [68Ga]Ga3+ and [177Lu]Lu3+, and mass spectrometric analysis confirmed site-selective coordination of Ga3+ by HBED-CC and Lu3+ by DOTA. All conjugates retained high PSMA-binding affinity in vitro, with [68Ga]Ga/[177Lu]Lu-2 and [68Ga]Ga/[177Lu]Lu-3 demonstrating enhanced cellular uptake in 22Rv1-FOLH-oe (PSMA overexpression) cells. In vivo PET/CT imaging and biodistribution studies revealed that [68Ga]Ga-2 exhibited favorable pharmacokinetics, including rapid background clearance and improved tumor retention. Importantly, [177Lu]Lu-2 achieved high tumor uptake, reaching 8.35%ID/g at 24 h post-injection, indicating effective tumor targeting and prolonged retention. These findings support the dual-chelator strategy as a promising platform for the development of next-generation PSMA-targeted radiotheranostic agents. By enabling efficient integration of diagnostic imaging and radionuclide therapy within a single molecule, this approach offers enhanced flexibility for radiopharmaceutical design while preserving favorable biological performance. The dual-chelator concept may facilitate the development of more effective companion diagnostic-therapeutic pairs and contribute to the advancement of precision oncology.

Background:spaceThis exploratory study aimed to evaluate the clinical feasibility and added diagnostic value of the heterodimeric agent Ga-68-NOTA-3P-TATE-RGD, targeting both SSTR2 and integrin alphavbeta3, in patients with radioactive-iodine-negative differentiated thyroid cancer (DTC), through a comparison with F-18-FDG PET/CT.Patients and Methods:spaceTwenty-two patients with radioactive-iodine-negative DTC underwent both Ga-68-NOTA-3P-TATE-RGD and F-18-FDG PET/CT within 1 week. Diagnostic performance and semiquantitative parameters were compared between the two agents. Based on the collected gene mutation data, a preliminary analysis was conducted on differences in PET uptake among different gene mutation types.Results:spaceA total of 265 and 295 lesions were detected on Ga-68-NOTA-3P-TATE-RGD and F-18-FDG PET/CT, respectively. Ga-68-NOTA-3P-TATE-RGD detected 45 exclusive lesions (12.71%), predominantly in bone (6 lesions) and brain (5 lesions), while F-18-FDG identified 75 exclusive lesions in lymph nodes (24 lesions) and lungs (51 lesions). The dual-targeted agent exhibited superior total specificity (92.3% vs 70.6%) and significantly higher tumor-background ratio for bone metastases [3.4 (2.6, 4.0) vs 2.3 (1.6, 2.9), P = 0.008]. For PET comparison of different gene mutations, Ga-68-NOTA-3P-TATE-RGD showed highest uptake in TERT promoter-mutant lesions (P < 0.01), while F-18-FDG had maximal uptake in BRAF-mutant lesions (P < 0.01).Conclusions:space(68)Ga-NOTA-3P-TATE-RGD PET/CT is feasible for radioactive-iodine-negative DTC, providing complementary diagnostic information to F-18-FDG with enhanced detection of bone and brain metastases. The intense uptake observed in lesions with TERT-associated aggressive subtypes supports potential utility for specific disease identification.

Prostate-specific membrane antigen (PSMA) is a well-established target for diagnostic imaging and radioligand therapy (RLT) in prostate cancer (PCa). This Perspective highlights PSMA-targeting agents incorporating the O-(carboxymethyl)-L-tyrosine scaffold, a versatile linker that enhances binding affinity and optimizes pharmacokinetics. The PET tracer [68Ga]Ga-P16-093 demonstrates high tumor uptake and low urinary background in clinical studies. Its success has enabled the development of therapeutic counterparts, including [177Lu]Lu-P17-087 which shows rapid in vivo kinetics, and [177Lu]Lu-P17-088 which exhibits improved tumor retention and prolonged circulation compared with [177Lu]Lu-PSMA-617 (PLUVICTO). The modular scaffold supports structural diversification, including alternative chelators and dual-targeting strategies. Incorporating a bisphosphonate moiety in P17-079 enables simultaneous targeting of PSMA and bone metastases. This adaptable platform facilitates the development of next-generation radiopharmaceuticals as theranostics for the treatment of PCa.

Incorporating a sulfur (VI)-fluoride exchange (SuFEx) chemistry-based linker, FAPI-based covalent targeted radioligand (CTR) showed better tumor binding affinity and longer retention time than FAPI-04 in animal studies. This study for the first time compared the lesion detection efficacy of [⁶⁸Ga]Ga-CTR-FAPI PET/CT and [⁶⁸Ga]Ga-FAPI-04 PET/CT in a radioiodine-refractory differentiated thyroid cancer clinical cohort. A single-center prospective comparative study was conducted, enrolling 40 RAIR-DTC patients with distant metastases. All patients underwent sequential [⁶⁸Ga]Ga-FAPI-04 PET/CT and [⁶⁸Ga]Ga-CTR-FAPI PET/CT examinations at a 24–48 h interval. Two experienced nuclear medicine physicians performed blinded visual analysis of the images to assess lesion detection status. Semi-quantitative analysis included the measurement of maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR) of lesions in different anatomical regions. The reference standard for lesion confirmation was a combination of conventional imaging, histopathological results (when feasible), and long-term clinico-radiological follow-up. The detection performances of the two imaging modalities were compared at the patient and lesion levels. Of the 40 enrolled patients, 37 had detectable metastatic lesions on both imaging modalities. Two patients had lesions exclusively detected by [⁶⁸Ga]Ga-CTR-FAPI PET/CT. [⁶⁸Ga]Ga-CTR-FAPI PET/CT achieved superior visual detection performance in 17.5

BACKGROUND:This exploratory study aimed to evaluate the clinical feasibility and added diagnostic value of the heterodimeric agent 68 Ga-NOTA-3P-TATE-RGD, targeting both SSTR2 and integrin α v β 3 , in patients with radioactive-iodine-negative differentiated thyroid cancer (DTC), through a comparison with 18 F-FDG PET/CT. PATIENTS AND METHODS:Twenty-two patients with radioactive-iodine-negative DTC underwent both 68 Ga-NOTA-3P-TATE-RGD and 18 F-FDG PET/CT within 1 week. Diagnostic performance and semiquantitative parameters were compared between the two agents. Based on the collected gene mutation data, a preliminary analysis was conducted on differences in PET uptake among different gene mutation types. RESULTS:A total of 265 and 295 lesions were detected on 68 Ga-NOTA-3P-TATE-RGD and 18 F-FDG PET/CT, respectively. 68 Ga-NOTA-3P-TATE-RGD detected 45 exclusive lesions (12.71%), predominantly in bone (6 lesions) and brain (5 lesions), while 18 F-FDG identified 75 exclusive lesions in lymph nodes (24 lesions) and lungs (51 lesions). The dual-targeted agent exhibited superior total specificity (92.3% vs 70.6%) and significantly higher tumor-background ratio for bone metastases [3.4 (2.6, 4.0) vs 2.3 (1.6, 2.9), P = 0.008]. For PET comparison of different gene mutations, 68 Ga-NOTA-3P-TATE-RGD showed highest uptake in TERT promoter-mutant lesions ( P < 0.01), while 18 F-FDG had maximal uptake in BRAF-mutant lesions ( P < 0.01). CONCLUSIONS:68 Ga-NOTA-3P-TATE-RGD PET/CT is feasible for radioactive-iodine-negative DTC, providing complementary diagnostic information to 18 F-FDG with enhanced detection of bone and brain metastases. The intense uptake observed in lesions with TERT-associated aggressive subtypes supports potential utility for specific disease identification.

Glioblastoma multiforme (GBM) remains an aggressive brain malignancy with dismal prognosis despite current standard-of-care therapies. The gastrin-releasing peptide receptor (GRPR) is overexpressed in gliomas and represents a potential therapeutic target. However, systemic radionuclide delivery is limited by poor tumor penetration and off-target toxicity. GRPR expression and prognostic relevance were analyzed using Chinese Glioma Genome Atlas and a clinical-trial dataset, respectively at the transcriptomic and protein levels. [177Lu]Lu-RM26, a lutetium-177-labeled GRPR-targeting antagonist, was evaluated in vitro, and administered intratumorally via convection-enhanced delivery in an orthotopic GL261Fluc+ glioblastoma model. Pharmacokinetic characteristics, including tumor retention and biodistribution, were evaluated by serial single-photon emission computed tomography and gamma-counting. Efficacy was assessed by tumor volume, bioluminescence signal, and overall survival. Safety was evaluated through body weight monitoring, neurological scoring, rotarod testing, hematology, and immunohistochemical staining. Mechanistic insights were obtained via bulk RNA-sequencing and Western blotting. Higher GRPR expression correlated with poorer-prognosis glioma subtypes and reduced survival. In vitro assays showed dose-dependent inhibition of GL261Fluc+ cell viability, proliferation, and invasion. Locoregional [177Lu]Lu-RM26 administration led to prolonged tumor retention (74.7 h), high absorbed dose (2.71 × 106 mGy·MBq− 1), and minimal off-target uptake. Treated mice exhibited marked tumor growth inhibition, reduced bioluminescence signal, and extended survival compared to controls. No significant short-term systemic toxicity or neurological impairment was observed. Transcriptome and Western blotting findings were consistent with DNA replication stalling and G2/M arrest. Locoregional [177Lu]Lu-RM26 therapy enables sustained, tumor-specific β-radiation with minimal systemic exposure, representing a promising locoregional strategy for GRPR-positive GBM.

Growth hormone-secreting pituitary adenoma (GHPA) can cause excessive growth hormone production, which can lead to clinical symptoms such as acromegaly. Tumor stem cells (TSCs) are postulated to play a significant role in the development of GHPA. We performed RNA sequencing on human pituitary adenoma stem-like cells (hPASCs) and matched bulk tumors to map a differentiation protein-protein interaction (PPI) network. The function of the C-X-C motif chemokine receptor-4 (CXCR4) gene was tested in hPASCs and the GH3 cell line. The CXCR4-based 68Ga-pentixafor tracer was assessed by the positron emission tomography and computed tomography (PET/CT) scanning of GHPA patients. A total of 685 differentially expressed genes were identified between hPASCs and differentiated tumor cells. Four clusters of genes were predicted, each carrying distinct biological functions. CXCR4 was pinpointed as a potential hub gene, which significantly affected the self-renewal and differentiation of hPASCs, as well as the proliferation, invasion, and migration of GH3 cells. CXCR4 suppression decreased intra-tumoral angiogenesis and epithelial-to-mesenchymal transition (EMT). CXCR4-based 68Ga-pentixafor was a more adaptive tracer than 18F-FDG in diagnosing GHPA using PET/CT. This study provides a comprehensive genetic profiling of hPASCs and substantiates the critical role of CXCR4 in tumorigenesis, highlighting its potential in translational medicine.

Rationale:[177Lu]Lu-D-Dan-Phe-PSMA ([177Lu]Lu-LNC1011) is a novel long-circulating prostate-specific membrane antigen (PSMA) therapeutic radioligand. This Phase I study aimed to investigate its safety, dosimetry, and initial treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods:This open-label, non-randomized, Phase I dose-escalation trial enrolled mCRPC patients with PSMA-positive lesions confirmed by PSMA PET/CT. A total of nine patients received [177Lu]Lu-LNC1011 at administered activity levels of 1.85 GBq, 2.78 GBq, and 3.70 GBq. Results:During the dose-limiting toxicity (DLT) observation period, no DLTs occurred in any activity group. The cumulative absorbed dose to organs increased with the injected activity. The effective dose to the whole body was 1.30E-01 ± 1.91E-02 mSv/MBq. The kidneys received the highest radiation dose (3.33 ± 1.09 Gy/GBq), consistent with the expected biodistribution of PSMA-targeted ligands. For salivary glands and red bone marrow, the absorbed doses were 1.70 ± 1.04 Gy/GBq and 0.11 ± 0.03 Gy/GBq, respectively. The mean absorbed dose to tumors was 12.29 ± 6.50 Gy/GBq. The effective half-life of [177Lu]Lu-LNC1011 was 49.44 ± 12.58 h in the whole body and 128.3 ± 62.79 h in tumor lesions. After two treatment cycles, the 3.70 GBq cohort (n = 3) demonstrated 100% PSA reduction (3/3), with 66.7% (2/3) achieving ≥50% PSA decline; simultaneously, Response Evaluation Criteria in PSMA PET/CT (RECIP) 1.0 assessment showed partial response (PR) in 66.7% (2/3) of patients and stable disease (SD) in 33.3% (1/3). Conclusion:[177Lu]Lu-LNC1011 was well tolerated across all dose levels, delivering high tumor-absorbed doses and prolonged tumor retention. The 3.70 GBq cohort demonstrated notable therapeutic efficacy. These favorable safety, dosimetry, and efficacy findings support the investigation of extended multi-cycle treatment with [¹⁷⁷Lu]Lu-LNC1011 at 3.70 GBq per cycle in future clinical studies.

We aimed to explore the value of prostate-specific membrane antigen (PSMA) and 18F-FDG PET/CT in efficacy evaluation and prognosis analysis for patients with metastatic castration-resistant prostate cancer (mCRPC) who underwent Lutetium-177-labeled Evans blue-modified PSMA (177Lu-EB-PSMA) therapy. This study retrospectively enrolled 35 mCRPC patients who received 177Lu-EB-PSMA therapy between January 2019 and April 2022, with follow-up data until December 2024. The correlation and predictive value of parameters derived from 68Ga-PSMA and 18F-FDG PET/CT with prostate-specific antigen (PSA) response rate, PSA progression-free survival (PSA-PFS), and overall survival (OS) were explored. Among the 35 patients, 27 and 15 received 2 and 3 cycles of 177Lu-EB-PSMA therapy, respectively. The best PSA response rate was 54.3 https://clinicaltrials.gov/study/NCT03780075 ;

Fibroblast activation protein (FAP) and integrin αvβ3 are attractive theranostic targets. We developed a dual-targeting radiotheranostic agent, 177Lu-DOTA-FAPI-RGD (177Lu-LNC1009), and conducted a first-in-human study to evaluate its safety, biodistribution, dosimetry, and preliminary efficacy in patients with advanced adenocarcinomas. Methods: LNC1009 was synthesized by conjugating an FAP inhibitor, an RGDfK peptide, and DOTA. Preclinical biodistribution was assessed in HT1080-FAP and U87MG xenografts. Nine patients with advanced solid tumors and positive 68Ga-FAPI-RGD PET/CT received 2.0 ± 0.3 GBq (range, 1.6-2.4 GBq) of 177Lu-LNC1009. Primary endpoints included biodistribution, dosimetry, and safety; efficacy was the secondary endpoint. Results: 177Lu-LNC1009 showed high radiochemical purity and stability, strong dual-target binding, and sustained tumor uptake with favorable tumor-to-background ratios. In patients, treatment was well-tolerated, with no grade 4 adverse events. The whole-body effective dose was 0.08 ± 0.02 mSv/MBq. Mean absorbed doses were 0.04 ± 0.01 Gy/GBq (red marrow), 0.50 ± 0.31 Gy/GBq (liver), and 0.31 ± 0.11 Gy/GBq (kidneys). Tumor-absorbed doses reached 6.10 ± 1.42 Gy/GBq (lung metastases) and 4.20 ± 0.84 Gy/GBq (lymph nodes). Grade 3 adverse events included thrombocytopenia (n = 3), leukopenia (n = 2), and anemia (n = 1). Partial responses occurred in 2 patients (22.2%), stable disease in 6 (66.7%), and progressive disease in 1 (11.1%), yielding an objective response rate of 22.2% and disease control rate of 88.9%. Conclusion: This first-in-human, dual-targeting radiopharmaceutical therapy agent 177Lu-LNC1009 demonstrated favorable dosimetry, high tumor radiation delivery, and encouraging preliminary efficacy across a variety of advanced solid tumors. Future ligand structural optimization and refined screening protocols are warranted to improve safety and further efficacy in multicycle, tumor-specific dose-escalation trials.

OBJECTIVE:Sjögren's disease (SjD) is an autoimmune exocrinopathy characterized by chronic glandular inflammation. Fibroblast activation protein (FAP) is a promising imaging biomarker for local inflammation. This study aims to evaluate the utility of [68Ga]Ga-FAPI PET/CT in SjD, assess its correlation with disease activity, and explore its role in monitoring treatment response. METHODS:This study enrolled SjD patients (2016 ACR-EULAR criteria), with cancer patients as controls. All SjD participants underwent EULAR Sjögren's Syndrome Patient Reported Index and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) assessments and serological testing; labial gland biopsies were additionally performed in a subset. The enrolled patients subsequently underwent longitudinal follow-up. RESULTS:[68Ga]Ga-FAPI-04 PET/CT imaging revealed significantly higher tracer uptake in the lacrimal, parotid and sublingual glands of SjD patients compared with controls (all P < 0.001), while no significant difference was observed in the submandibular gland. Receiver operating characteristic analysis demonstrated high diagnostic performance, particularly for parotid gland parameters [maximum standardized uptake value (SUVmax): AUC = 0.89; 95% CI: 0.84-0.94; P < 0.001]. After correcting for multiple comparisons, parotid gland uptake remained significantly and positively correlated with ESR (r = 0.51-0.58, P < 0.05) and RF (r = 0.50-0.57, P < 0.05). Regarding disease activity, only parotid total lesion fibroblast (TLF) activation demonstrated a significant correlation with the ESSDAI score (r = 0.48, P < 0.05). Follow-up imaging in nine patients showed that glucocorticoid therapy was associated with concurrent reductions in clinical scores and salivary gland FAPI uptake. CONCLUSION:[68Ga]Ga-FAPI PET/CT noninvasively assesses fibroblast activation in SjD, correlates with disease activity and treatment response, and supports its potential clinical utility. TRIAL REGISTRATION:This study has been registered online at NIH ClinicalTrial.gov (NCT07062523).

Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal low-grade non-Hodgkin lymphoma that extremely rarely localises to the mediastinum. A 34-year-old female with chronic arthralgia, sicca and rash was found to have a well-demarcated mediastinal cystic mass with equivocal nodular enhancement within the cystic wall on chest CT during a workup for Sjögren's syndrome. Subsequent 68Ga-Pentixafor-PET/CT revealed focal uptake increase within the cystic capsule. The patient underwent thoracoscopic resection of the mediastinal lesion, and pathology revealed MALT lymphoma in the wall of a thymic cyst. This case highlights that 68Ga-pentixafor PET/CT could be valuable for the non-invasive detection of occult thymic MALT lymphoma. Trial Registration: ClinicalTrials.gov. (www.clinicaltrials.gov, NCT06086327).

Radiotheranostics holds transformative potential for precision oncology by integrating diagnostic imaging with targeted radionuclide therapy. However, advancements in this field are significantly hindered by the limited availability of high-affinity ligands that are capable of engaging challenging cell-surface antigens, particularly flat, low-druggability targets such as programmed death-ligand 1 (PD-L1). Here, we overcome this barrier through de novo discovery and rational engineering of a disulfide-directed multicyclic peptide (DDMP), dmp10, which achieves a picomolar affinity for PD-L1 by leveraging conformationally constrained structural scaffolds. By combining disulfide-directed library design with iterative directed evolution, we successfully generated dmp10, a ∼3 kDa multicyclic peptide that establishes unprecedented shape complementarity to the expansive binding interface of PD-L1. Preclinical evaluations demonstrated that 68Ga-labeled dmp10 enables high-contrast PET imaging of PD-L1+ tumors in murine models, achieving a tumor uptake of 13.27 %ID/g at 4 h post-injection. The therapeutic counterpart, 177Lu-labeled dmp10, effectively eradicated 92.47% of established tumors in tumor models while sparing healthy tissues, thereby validating its dual radiotheranostic utility. The translational relevance of our findings was further confirmed in a first-in-human pilot study, where 68Ga-labeled dmp10 was well tolerated and allowed visualization of PD-L1+ lesions in patients with solid tumors. This work not only establishes DDMPs as a versatile platform for targeting geometrically complex antigens but also delivers a promising radiotheranostic agent that bridges molecular imaging and precision radionuclide therapy for PD-L1-driven malignancies. Our findings advance current strategies for designing ultrahigh-affinity peptide binders and underscore the untapped potential of multicyclic architectures in overcoming longstanding challenges in cancer theranostics.

Gastrointestinal stromal tumors (GISTs) are the most common stromal tumors in the gastrointestinal tract. This study was designed to evaluate a gastrin-releasing peptide receptor antagonist PET tracer, [68Ga]Ga-NOTA-RM26, and compare it with [18F]FDG PET/CT in the assessment of patients with GISTs. Methods: With institutional review board approval and informed consent, 30 patients with suspected or proven GISTs based on abdominal CT or gastroscopy were recruited. All patients underwent [68Ga]Ga-NOTA-RM26 and [18F]FDG PET/CT scans. Pathology and other patient information were collected. Results: No radiopharmaceutical-related adverse events were observed in the patients. In total, 18 lesions in 16 patients were diagnosed as GIST, 3 patients were diagnosed with schwannoma, and 4 patients were diagnosed with leiomyoma. In 18 GISTs, the mean SUVmax of [68Ga]Ga-NOTA-RM26 PET was significantly higher than that of [18F]FDG PET (17.07 ± 19.57 vs. 2.28 ± 1.65; P < 0.01), and [68Ga]Ga-NOTA-RM26 PET/CT had a higher tumor detection rate than did [18F]FDG PET/CT (88.9% vs. 50%; P < 0.01). The uptake of [68Ga]Ga-NOTA-RM26 in GISTs was significantly higher than that in 2 other benign tumors (leiomyoma or schwannoma) (17.07 ± 19.57 vs. 4.23 ± 1.77; P = 0.014). With the SUVmax cutoff value of 6.0, the sensitivity of 68Ga-NOTA-RM26 PET/CT in diagnosing GISTs is 72% and the specificity is 85.7%. Conclusion: Compared with [18F]FDG PET/CT, [68Ga]Ga-NOTA-RM26 PET/CT is a promising and effective imaging modality for the detection of GISTs.

[ 18 F]FDG PET/CT is widely used in the diagnosis and treatment monitoring of lung cancer, yet its ability to differentiate histologic heterogeneity remains limited. In this case, a 75-year-old man presented with a large pulmonary mass adjacent to a small satellite lesion. Bronchoscopic biopsy of the main lesion revealed small-cell lung cancer (SCLC). After first-line chemotherapy, the primary lesion showed partial response, while the smaller nodule remained stable. Posttreatment [ 18 F]FDG and [ 68 Ga]Ga-DOTA-3P-TATE-RGD PET/CT demonstrated divergent uptake patterns. Rebiopsy of the nodule with discordant tracer uptake confirmed squamous cell carcinoma, indicating synchronous double primary lung cancers. The dual-targeted tracer PET/CT guided precise biopsy and individualized therapy.

Heterotopic pancreas is a congenital malformation of various shapes and origins and is usually asymptomatic, which can simulate benign tumors on imaging, so diagnosis usually requires biopsy or surgical resection. We present a young woman with abdominal distension who was found to have a gastric mass that was suspected to be a gastrointestinal stromal tumor (GIST) by gastroscopy and enhanced CT. 68 Ga-NOTA-RM26 PET/CT, a novel imaging modality targeting the gastrin-releasing peptide receptor (GRPR), also showed intense uptake in the mass. Pathology results of the resected mass demonstrated pancreatic tissue, supporting the diagnosis of heterotopic pancreas.

Purpose The aim of this study was to investigate the value of 68Ga-NOTA-RM26 (68Ga-RM26), a gastrin-releasing peptide receptor–targeting antagonist labeled with the radionuclide 68Ga, in the diagnosis of high-grade gliomas and in combination with multiregional biopsies using PET/CT. Patients and Methods After institutional review board approval and informed consent, a total of 35 patients with suspected glioma lesions were enrolled in this study. All patients underwent 68Ga-RM26 PET/CT scans within 2 weeks before surgery. Results There were 8 grade II gliomas, 6 grade III gliomas, and 18 grade IV gliomas in a total of 32 glioma lesions. 68Ga-RM26 PET/CT diagnosed 74.4% of lesions (27/32) of all glioma tumor types, and almost all high-grade gliomas were successfully diagnosed (23/24, 95.8%). Among the 9 negative glioma lesions, there were 8 low-grade gliomas (grade II). There was a significantly higher SUVmax, SUVmean, and the lesion-to-background ratio (T/B ratio) in high-grade gliomas compared with low-grade gliomas (P < 0.001). In addition, there was a high correlation between the immunohistochemical staining score of gliomas and parameters (SUVmax, SUVmean, and T/B ratio) on 68Ga-RM26 PET/CT (P < 0.001), and verified by immunohistochemical staining on multiple-point samples of glioma lesions guided by 68Ga-RM26 PET/CT. Conclusions 68Ga-RM26 could noninvasively diagnose high-grade gliomas and be a promising PET tracer for predicting glioma grading before surgery. This pilot study indicated that the uptake of 68Ga-RM26 correlates with WHO grade in glioma, and preoperative 68Ga-RM26 PET/CT may be helpful to guide multiple-point biopsy of gliomas.

Solitary fibrous tumor (SFT) is a rare sarcoma of mesenchymal origin. Although generally benign, SFTs carry the risk of recurrence and metastasis, with limited effective treatment options. The aims of this study are to compare the performance of fibroblast activation protein inhibitor (FAPI), [68Ga]Ga-DOTA-FAPI-04 (denoted as [68Ga]Ga-FAPI-04), and conventional [18F]FDG PET/CT in patients with recurrent or metastatic SFTs head to head and to preliminarily explore the value of FAP-targeted radiopharmaceutical therapy with 177Lu for SFT patients. Methods: Thirty-one participants (21 men, 44 ± 13 y) with suspected recurrent or metastatic SFTs underwent both [18F]FDG and [68Ga]Ga-FAPI-04 PET/CT within 1 wk. The positive-lesion rates of the 2 PET/CT scans in the different organs involved and the uptake values (SUVmax) were compared. Four patients with high [68Ga]Ga-FAPI-04 uptake received single-cycle therapy of 2.22 GBq of a [177Lu]Lu-labeled, FAP-targeted radiopharmaceutical, [177Lu]Lu-Evans blue-FAPI, and were followed up for 4 mo. Results: In 522 local recurrences and distant metastases in the 31 patients, [68Ga]Ga-FAPI-04 PET detected significantly more lesions than did [18F]FDG (87.0% vs. 45.4%, P < 0.001). In terms of lesion uptake values, [68Ga]Ga-FAPI-04 PET showed a mean SUVmax higher than that of [18F]FDG in most recurrence or metastatic organs (bone, lung, central nervous system, pancreas, and pleura, P < 0.001; kidney and abdominopelvic cavity, P = 0.001; muscle and pericardium, P < 0.05). Four patients tolerated [177Lu]Lu-Evans blue-FAPI well. The total-body absorbed dose and the effective dose were 4.02E-01 ± 3.54E-02 Gy and 4.01E+02 ± 4.18E+01 mSv, respectively. Subsequent follow-up with [68Ga]Ga-FAPI-04 PET showed that these patients were in stable condition. Conclusion: [68Ga]Ga-FAPI-04 may be a promising PET agent for the assessment of SFTs. Given the lack of effective treatments for advanced SFTs, high FAP expression in this type of tumor is expected to become a potential treatment target.