DPA714 PET Imaging Shows That Inflammation of the Choroid Plexus Is Active in Chronic-Phase Intracerebral Hemorrhage.

PURPOSE: Our aims were to investigate the presence of choroid plexus (CP) inflammation in chronic-phase intracerebral hemorrhage (ICH) patients and to characterize any inflammatory cells in the CP. PATIENTS AND METHODS: An in vivo 18 F-DPA714 PET study was undertaken in 22 chronic-phase ICH patients who were admitted to the First Affiliated Hospital of Fujian Medical University or Tianjin Medical University General Hospital from April 2017 to June 2020. Ten control participants with nonhemorrhagic central nervous system diseases were included. Choroid plexus 18 F-DPA714 uptake was calculated as the average SUVR. To aid the interpretation of the 18 F-DPA714 uptake results at the CP level, Cy5-DPA714 in vivo imaging and immunofluorescence staining were used to show the presence of CP inflammation in an ICH mouse model during the chronic phase (14 weeks after ICH). Then immunofluorescence staining against translocator protein and other specific biomarkers was used to characterize the cells present in the inflamed CP of ICH mice in the chronic phase. RESULTS: PET imaging showed that CP DPA714 SUVRs in chronic-phase ICH patients were higher than in controls (mean CP SUVR ± SD; ICH group: 1.05 ± 0.35; control group: 0.81 ± 0.21; P = 0.006). Immunofluorescence staining of the CP in ICH model mice identified a population of CD45 + immune cells, peripheral monocyte-derived CD14 + cells, CD68 + phagocytes, and CD11b + resident microglia/macrophages expressing translocator protein, possibly contributing to the increased 18 F-DPA714 uptake. CONCLUSIONS: Our study shows that CP DPA714 uptake in chronic-phase ICH patients was higher than that of participants with nonhemorrhagic central nervous system diseases, which means that CP inflammation is still active in chronic-phase ICH patients.

Visualization of Thromboinflammation by 18F-DPA-714 PET in a Stroke Patient.

ABSTRACT: A 44-year-old man who presented with progressive right limb weakness was diagnosed with ischemic stroke. He was referred for 18F-DPA-714 PET/CT for evaluation of the disease. 18F-DPA-714 PET/CT showed increased uptake of the intracranial thrombus. This DPA-714-avid thrombus highly suggested the involvement of immune cells in the extension of the clot resulting in neurological deterioration. This present case suggested that 18F-DPA-714 PET might be a promising tracer in visualizing thromboinflammation in vivo.

Head-to-Head Comparison of 68Ga-NODAGA-JR11 and 68Ga-DOTATATE PET/CT in Patients with Metastatic, Well-Differentiated Neuroendocrine Tumors: Interim Analysis of a Prospective Bicenter Study.

The current study aimed to compare 68Ga-NODAGA-Cpa-cyclo(d-Cys-amino-Phe-hydroorotic acid-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)-d-Tyr-NH2 (JR11) and 68Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors. Methods: A prospective bicenter study aimed at enrolling 100 patients with histologically proven, metastatic or unresectable, well-differentiated neuroendocrine tumors was conducted. The first 48 patients represented the study cohort. Each patient received 68Ga-DOTATATE on the first day and 68Ga-NODAGA-JR11 on the second day. Whole-body PET/CT scans were performed at 40-60 min after injection. Normal-organ uptake, lesion numbers, lesion uptake, and sensitivity were compared. The potential impact on clinical management was also determined. Results: Overall, 68Ga-NODAGA-JR11 demonstrated lower background uptake in normal organs. Compared with 68Ga-DOTATATE, 68Ga-NODAGA-JR11 detected significantly more liver lesions (673 vs. 584, P = 0.002). The target-to-background ratio of liver lesions was significantly higher on 68Ga-NODAGA-JR11 (6.4 ± 8.7 vs. 3.1 ±2.6, P = 0.000). Comparable uptake was observed for primary tumors, bone lesions, and lymph node metastases. In total, 180 lesions were detected on conventional imaging in 15 patients; 165 and 139 lesions of them were positive on 68Ga-NODAGA-JR11 and 68Ga-DOTATATE, leading to a sensitivity of 91.7% and 77.2%, respectively. In 14.5% (7/48) of patients, 68Ga-NODAGA-JR11 PET might have a potential impact on clinical management. Conclusion: 68Ga-NODAGA-JR11 shows better sensitivity and a higher target-to-background ratio than 68Ga-DOTATATE. The detection of more lesions by the antagonist may have a potential impact on clinical management in a subgroup of patients.

Nuclear Medicine Application of Pentixafor/Pentixather Targeting CXCR4 for Imaging and Therapy in Related Disease.

C-X-C-motif chemokine receptor 4 (CXCR4) is a novel predictive biomarker for metastasis and poor prognosis in individuals with malignancies. CXCL12 is the only cognate ligand of CXCR4. CXCL12/CXCR4 signaling pathways are involved in the cross-talk among cancer cells, T cells, stromal cells, and their microenvironments, including the regulation and direction of T cell migration (chemotaxis), proliferation, and differentiation of immature progenitor stem cells. As CXCR4 overexpression is related to tumor prognosis, it is essential to quantitatively evaluate CXCR4 expression levels in vivo. 68Ga-Pentixafor, as a radiolabeled tracer, shows high specificity and affinity for CXCR4 in tumors. Thus, CXCR4-directed imaging with 68Ga-Pentixafor has been investigated to evaluate CXCR4 expression in patients non-invasively. In recent years, many small cohorts, including those of individuals with hematologic malignancies, solid tumors, and cardiovascular and infectious diseases, have been reported. So far, 68Ga-Pentixafor has been used successfully in individuals with hematologic malignancies. In addition, Lutetium-177 (177Lu) or Yttrium-90 (90Y)-labeled Pentixather (an analog of Pentixafor) suggested high potential applicability in tumor endoradiotherapy (ERT) with CXCR4 overexpression. Patients with advanced-stage multiple myeloma, refractory acute leukemia, and diffuse large B-cell lymphoma received a certain amount of 177Lu-Pentixather or 90Y-Pentixather. This review aimed to overview the current CXCR4-directed positron emission computed tomography (PET) molecular imaging based on Pentixafor in several diseases and ERT.

Recent Advances in 18F-Labeled Amino Acids Synthesis and Application.

Radiolabeled amino acids are an important class of agents for positron emission tomography imaging that target amino acid transporters in many tumor types. Traditional 18F-labeled amino acid synthesis strategies are always based on nucleophilic aromatic substitution reactions with multistep radiosynthesis and low radiochemical yields. In recent years, new 18F-labeling methodologies such as metal-catalyzed radiofluorination and heteroatom (B, P, S, Si, etc.)-18F bond formation are being effectively used to synthesize radiopharmaceuticals. This review focuses on recent advances in the synthesis, radiolabeling, and application of a series of 18F-labeled amino acid analogs using new 18F-labeling strategies.

[68Ga]Ga-FAPI PET/CT Improves the T Staging of Patients with Newly Diagnosed Nasopharyngeal Carcinoma: A Comparison with [18F]F-FDG.

PURPOSE: This study aimed to explore the value of [68Ga]Ga-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in the initial staging of patients with newly diagnosed nasopharyngeal carcinoma (NPC), compared with 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) PET/CT. MATERIALS AND METHODS: Forty-seven treatment-naïve patients with newly diagnosed NPC underwent magnetic resonance imaging (MRI), [68Ga]Ga-DOTA-FAPI-04 PET/CT and [18F]F-FDG PET/CT within 1 week. The diagnostic efficiency of all imaging modalities for evaluating primary tumour extension was compared from the two aspects of soft tissue and bony structure involvement. The accuracy of two PET/CT methods for diagnosing cervical lymph node (CLN) metastases was compared, and MRI served as the standard reference. T and N stages were assessed by MRI, [68Ga]Ga-FAPI PET/CT and [18F]F-FDG PET/CT. Immunohistochemical (IHC) staining for FAP was conducted in 22 of the patients. RESULTS: [68Ga]Ga-FAPI PET/CT outperformed [18F]F-FDG PET/CT in the assessment of primary tumour invasion in the cavernous sinus (10 vs. 1, p < 0.001) and bony structures (207 vs. 177, p < 0.001). Compared with MRI, [68Ga]Ga-FAPI PET/CT upgraded and underestimated T stage in 13 and 2 patients, while [18F]F-FDG PET/CT upgraded and underestimated T stage in 5 and 13 patients. However, [68Ga]Ga-FAPI PET/CT was inferior to [18F]F-FDG PET/CT in diagnosing positive CLNs based on the analyses of patients, neck sides, neck levels and individual nodes. [68Ga]Ga-FAPI PET/CT changed therapeutic schedules in 8 patients because of stage group changes. The presence of FAP with high quantity and intensity in cancer-associated fibroblasts (CAFs) was confirmed in all tumour specimens. CONCLUSION: [68Ga]Ga-FAPI PET/CT outperformed [18F]F-FDG PET/CT in detecting the cavernous sinus and bony structure involvement of primary NPC tumours, suggesting its value in improving T staging and therapeutic regimen selection. However, the performance of [68Ga]Ga-FAPI PET/CT is less promising for N staging because it detected fewer positive CLNs than [18F]F-FDG PET/CT.

68Ga-DOTA-FAPI-04 PET/CT imaging in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients.

OBJECTIVE: This study aimed to assess the potential of 68Ga-DOTA-FAPI-04 PET/CT for the detection of the radioiodine-refractory differentiated thyroid cancer (RR-DTC) lesions. METHODS: We analyzed the 68Ga-DOTA-FAPI-04 PET/CT imaging data of 24 RR-DTC patients (7 men and 17 women; 49.6 ± 10.5 year). Clinical data were collected including history, last post-therapeutic radioiodine whole body scan, contemporary CT, thyroglobulin, and antithyroglobulin. Target lesions were selected and measured by the RECIST 1.1. The mean growth rates of the target lesions in the past 6 months were recorded. Tumor uptake of lesions were quantified by SUVmax and the tumor-to-background ratios. The correlation between SUVmax and target lesion growth rate and thyroglobulin was analyzed. RESULTS: On patient-based analysis, positive metastases were detected in 87.5% (21/24) patients. Except for the lymph node (LN) metastasis of 3 patients (patient 6, 12 and 17#) and the lung metastasis of another 3 patients (patient 9, 13 and 21#), most of the lesions were positive on 68Ga-DOTA-FAPI-04 PET/CT images, including LN metastasis and distant metastasis such as lung, bone and pleura. There were altogether 33 target lesions including 30 lung metastases and 3 LN metastases with the mean SUVmax and the growth rate were 4.25 and 6.51%, respectively. SUVmax was statistically associated with the growth rates of the target lesions (p = 0.047). No statistically significant correlation was found between the SUVmax and the serum thyroglobulin levels (p = 0.139). CONCLUSIONS: 68Ga-DOTA-FAPI-04 PET/CT has a promising detection rate for RR-DTC metastasis. The FAPI uptake of the tumor may provide a potential therapeutic target for RR-DTC. TRIAL REGISTRY: NIH Clinical Trials.gov (NCT04499365).

Accurate preoperative staging with [68Ga]Ga-FAPI PET/CT for patients with oral squamous cell carcinoma: a comparison to 2-[18F]FDG PET/CT.

OBJECTIVE: To evaluate the potential value of [68Ga]Ga-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) in preoperative staging for patients with oral squamous cell carcinoma (OSCC) as compared to 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET/CT. METHODS: Thirty-six treatment-naïve patients with OSCC who underwent 2-[18F]FDG and [68Ga]Ga-FAPI PET/CT for preoperative staging were enrolled. The maximum standardised uptake value (SUVmax) of the primary tumour and suspected cervical metastatic lymph nodes, and the tumour-to-background ratio (TBR) of the primary tumour, were measured. The accuracy of two imaging modalities for preoperative diagnosis of metastatic lymph nodes was analysed. Histopathology served as the standard of reference. RESULTS: Thirty-seven primary lesions of 36 patients were accurately detected by both [68Ga]Ga-FAPI and 2-[18F]FDG PET/CT. Regarding primary tumours, the SUVmax and TBR of the two imaging modalities in stage T3-T4 were significantly higher than those of stage T1-T2 (all p < 0.05). On the patient analysis, the accuracy for the evaluation of N1-N3 neck status was 52.6% (10/19) for [68Ga]Ga-FAPI PET/CT and 57.9% (11/19) for 2-[18F]FDG PET/CT. Notably, the accuracy for the evaluation of the N0 neck status between [68Ga]Ga-FAPI and 2-[18F]FDG PET/CT was 100% (17/17) and 29% (5/17), respectively. Based on the patient, neck side and neck level, [68Ga]Ga-FAPI PET/CT resulted in higher specificity and accuracy in diagnosing metastatic neck lymph nodes than 2-[18F]FDG PET/CT (all p < 0.05). CONCLUSION: [68Ga]Ga-FAPI PET/CT is a promising tool for preoperative staging of OSCC, and appears to reduce the false positivity seen with 2-[18F]FDG PET/CT for the detection of neck lymph node metastases. KEY POINTS: • [68Ga]Ga-FAPI PET/CT is a promising tool targeting cancer-associated fibroblasts with comparable diagnostic performance to 2-[18F]FDG PET/CT for identifying the primary lesions of OSCC. • [68Ga]Ga-FAPI PET/CT showed higher specificity and accuracy for the evaluation of neck lymph node metastases of OSCC than 2-[18F]FDG PET/CT, especially for N0 neck status.

Pleural Metastasis of Papillary Thyroid Cancer Depicted by 68Ga-FAPI PET/CT.

ABSTRACT: A 43-year-old woman with history of papillary thyroid cancer status post total thyroidectomy and neck dissection and multiple radioiodine therapy developed dyspnea and cough. CT scan of the chest showed left pleural thickening and pleural effusion. The pathology from pleural biopsy demonstrated the metastases from papillary thyroid cancer. 68Ga-fibroblast activation protein inhibitor PET/CT showed inhomogeneously increased uptake of fibroblast activation protein inhibitor in the thickened pleura.

Chinese patients with hereditary spastic paraplegias (HSPs): a protocol for a hospital-based cohort study.

INTRODUCTION: Hereditary spastic paraplegias (HSPs) are uncommon but not rare neurodegenerative diseases. More than 100 pathogenic genes and loci related to spastic paraplegia symptoms have been reported. HSPs have the same core clinical features, including progressive spasticity in the lower limbs, though HSPs are heterogeneous (eg, clinical signs, MRI features, gene mutation). The age of onset varies greatly, from infant to adulthood. In addition, the slow and variable rates of disease progression in patients with HSP represent a substantial challenge for informative assessment of therapeutic efficacy. To address this, we are undertaking a prospective cohort study to investigate genetic-clinical characteristics, find surrogates for monitoring disease progress and identify clinical readouts for treatment. METHODS AND ANALYSIS: In this case-control cohort study, we will enrol 200 patients with HSP and 200 healthy individuals in parallel. Participants will be continuously assessed for 3 years at 12-month intervals. Six aspects, including clinical signs, genetic spectrum, cognitive competence, MRI features, potential biochemical indicators and nerve electrophysiological factors, will be assessed in detail. This study will observe clinical manifestations and disease severity based on different molecular mechanisms, including oxidative stress, cholesterol metabolism and microtubule dynamics, all of which have been proposed as potential treatment targets or modalities. The analysis will also assess disease progression in different types of HSPs and cellular pathways with a longitudinal study using t tests and χ2 tests. ETHICS AND DISSEMINATION: The study was granted ethics committee approval by the first affiliated hospital of Fujian Medical University (MRCTA, ECFAH of FMU (2019)194) in 2019. Findings will be disseminated via presentations and peer-reviewed publications. Dissemination will target different audiences, including national stakeholders, researchers from different disciplines and the general public. TRIAL REGISTRATION NUMBER: NCT04006418.

Burkitt Lymphoma/Leukemia Presented on 68Ga-Pentixafor and 18F-FDG PET/CT.

ABSTRACT: An 18-year-old man with newly diagnosed Burkitt lymphoma/leukemia was referred for 18F-FDG and 68Ga-Pentixafor PET/CT. 68Ga-Pentixafor PET/CT revealed similar radioactivity uptake pattern to the 18F-FDG PET/CT in superior phrenic lymph node, ascending colon, ileocecum, peritoneal, marrow, and spleen. This case highlighted that it might be interesting to further investigate the role of 68Ga-Pentixafor PET/CT imaging in staging, treatment evaluation, and especially the feasibility of CXCR4-directed radioligand therapy in Burkitt lymphoma with positive expression of CXCR4.

68Ga-FAPI and 18F-PET/CT Images in Intestinal Tuberculosis.

ABSTRACT: A 28-year-old woman presented with abdominal pain, bowel dysfunction, and weight loss for 3 months. 18F-FDG PET/CT revealed multiple hypermetabolic lesions in the intestines and peritoneal thickening/caking with moderate FDG activity. 68Ga-FAPI PET/CT showed intense FAPI uptake in the aforementioned FDG-avid lesions and a larger number of abnormal foci with intense FAPI uptake in the peritoneum than that shown in 18F-FDG images. Endoscopy-guided biopsy from the colonic mucosa was consistent with tuberculosis. The positive findings of 68Ga-FAPI in the current case highlighted that 68Ga-FAPI may have value in the evaluation of intestinal tuberculosis.

Non-invasive assessment of heterogeneity of gliomas using diffusion and perfusion MRI: correlation with spatially co-registered PET.

BACKGROUND: Heterogeneity of gliomas challenges the neuronavigated biopsy and oncological therapy. Diffusion and perfusion magnetic resonance imaging (MRI) can reveal the cellular and hemodynamic heterogeneity of tumors. Integrated positron emission tomography (PET)/MRI is expected to be a non-invasive imaging approach to characterizing glioma. PURPOSE: To evaluate the value of apparent diffusion coefficient (ADC), cerebral blood volume (CBV), and spatially co-registered maximal standard uptake value (SUVmax) for tissue characterization and glioma grading. MATERIAL AND METHODS: Thirty-seven consecutive patients with pathologically confirmed gliomas were retrospectively investigated. The relative minimum ADC (rADCmin), relative maximal ADC (rADCmax), relative maximal rCBV (rCBVmax), the relative minimum rCBV (rCBVmin), and the corresponding relative SUVmax (rSUVmax) were measured. The paired t-test was used to compare the quantitative parameters between different regions to clarify tumor heterogeneity. Imaging parameters between WHO grade IV and grade II/III gliomas were compared by t-test. The diagnostic efficiency of multiparametric PET/MRI was analyzed by receiver operating characteristic (ROC) curve. RESULTS: The values of rSUVmax were significantly different between maximal diffusion/perfusion area and minimum diffusion/perfusion area (P < 0.001/P < 0.001) within tumor. The values of rADCmin (P < 0.001), rCBVmax (P = 0.002), and corresponding rSUVmax (P = 0.001/P < 0.001) could be used for grading gliomas. The areas under the ROC curves of rSUVmax defined by rADCmin and rCBVmax were 0.89 and 0.91, respectively. CONCLUSION: Diffusion and perfusion MRI can detect glioma heterogeneity with excellent molecular imaging correlations. Regions with rCBVmax suggest tissues with the highest metabolism and malignancy for guiding glioma grading and tissue sampling.

Reference values of mandibular condylar growth activity: a study of SUVmax with quantitative bone SPECT/CT.

OBJECTIVE: To assess the condylar growth activity (CGA) with quantitative bone single photon emission computed tomography/computed tomography (SPECT/CT) to establish reference values of maximum standardized uptake value (SUVmax) and cutoff values for identifying active unilateral condylar hyperplasia (UCH) in different ages. METHODS: We analyzed the CGA of 58 UCH patients and that of 125 volunteers as a control group by SUVmax of quantitative bone SPECT/CT imaging. The SUVmax and the uptake difference between bilateral condyles among different age groups were analyzed. SUVmax cutoff values for detecting active condyle were calculated by receiver operating characteristic curve analysis. RESULTS: The condylar SUVmax in 10-19, 20-29, 30-39, 40-49 and 50-59 years old groups of volunteers were 6.24 ± 1.39, 4.76 ± 0.98, 3.23 ± 0.64, 3.00 ± 0.61 and 2.90 ± 0.53, respectively. The uptake difference between bilateral condyles in the control group was 3.84% ± 1.71%. The affected condylar SUVmax was significantly higher than that of the contralateral condyle in active UCH patients (6.03 ± 2.85 vs. 3.96 ± 1.07; Z = -5.264; P = 0.000). SUVmax of the affected condyles in active UCH patients was not statistically higher than condylar SUVmax in the corresponding age group (6.03 ± 2.85 vs. 5.50 ± 1.41; Z = -0.173; P = 0.863). SUVmax of the unaffected condyles was significantly lower than condylar SUVmax in the corresponding age group (3.96 ± 1.07 vs. 5.50 ± 1.41; Z = -5.833; P = 0.000). SUVmax cutoff values for identifying active condyle were 6.26 and 4.53 in patients of 13-19 and 20-29 years old, respectively. CONCLUSIONS: The condylar SUVmax varied with age. Different cutoff values of condylar SUVmax should be employed for diagnosing active UCH for patients in different ages.

A prospective randomized, double-blind study to evaluate the diagnostic efficacy of 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 in patients with well-differentiated neuroendocrine tumors: compared with 68Ga-DOTATATE.

PURPOSE: The purpose of this study is to evaluate the diagnostic efficacy of 68 Ga-NODAGA-LM3 and 68 Ga-DOTA-LM3 and compare them with 68 Ga-DOTATATE in patients with well-differentiated neuroendocrine tumors. METHODS: Patients were prospectively recruited and equally randomized into two arms: Arm A, patients would undergo a whole-body 68 Ga-NODAGA-LM3 PET/CT scan on the 1st day and 68 Ga-DOTATATE PET/CT scan on the 2nd day; Arm B, patients would undergo a whole-body 68 Ga-DOTA-LM3 PET/CT scan on the 1st day and 68 Ga-DOTATATE PET/CT scan on the 2nd day. Biodistribution in normal organs, lesion detection ability, and tumor uptake were compared between antagonist and agonist in each arm. RESULTS: A total of 40 patients with well-differentiated NETs, 20 in each arm, were recruited in the study. 68 Ga-NODAGA-LM3 showed a similar pattern as 68 Ga-DOTATATE, while 68 Ga-DOTA-LM3 demonstrated significantly lower uptake in almost all normal organs compared to 68 Ga-DOTATATE. Both 68 Ga-NODAGA-LM3 and 68 Ga-DOTA-LM3 showed superiority in lesion detection compared to 68 Ga-DOTATATE on lesion-based and patient-based comparison. 68 Ga-NODAGA-LM3 showed a significantly higher tumor uptake (median SUVmax 29.1 versus 21.6, P < 0.05) and tumor-to-background ratio (median tumor-to-liver ratio 5.0 versus 2.9, P < 0.05) compared to 68 Ga-DOTATATE. 68 Ga-DOTA-LM3 showed comparable uptake (median SUVmax 16.1 versus 17.8, P = 0.714) and higher tumor-to-background ratio (median tumor-to-liver ratio 5.2 versus 2.1, P < 0.05). CONCLUSION: Both 68 Ga-NODAGA-LM3 and 68 Ga-DOTA-LM3 are promising SSTR2 antagonists for neuroendocrine tumors. They demonstrated superiority in diagnostic efficacy compared to agonist 68 Ga-DOTATATE. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04318561.

Fibroblast Activation Protein-α Responsive Peptide Assembling Prodrug Nanoparticles for Remodeling the Immunosuppressive Microenvironment and Boosting Cancer Immunotherapy.

Checkpoint blockade immunotherapy has broad application prospects in the clinical treatment of malignant tumors. However, the low response rate of the checkpoint blockade is due to low tumor immunogenicity and immunosuppression within the tumor microenvironment. Herein, the authors design an amphiphilic bifunctional PD-1/PD-L1 peptide antagonist PCP, and co-deliver doxorubicin (DOX) and R848 through co-assembly of a multi-agent prodrug (PCP@R848/DOX), which can be specifically cleaved by fibroblast activation protein-α (FAP-α) in the tumor stroma. Upon reaching the tumor tissue, the PCP@R848/DOX prodrug nanostructure is disassembled by FAP-α. The localized release of DOX and R848 triggers immunogenic cell death (ICD) and reprograms tumor-associated macrophages (TAMs) to elicit antitumor immunity. Furthermore, sustained release of PD-1 or PD-L1 peptide antagonists mediates the PD-L1 pathway blockade for further propagated activation of cytotoxic T lymphocytes. Notably, a tumor microenvironment activatable prodrug nanoparticle is presented for triple-modality cancer therapy that functions by simultaneously activating ICD and altering the phenotype of TAMs when combined with PD-1 blockade therapy, which efficiently elicits a strong systemic antitumor immune response. This strategy may emerge as a new paradigm in the treatment of cancer by combination immunotherapy.

CXCR4-Directed PET/CT with [68Ga]Pentixafor in Central Nervous System Lymphoma: A Comparison with [18F]FDG PET/CT.

PURPOSE: This study aimed to evaluate the value of [68 Ga]Pentixafor PET/CT for the detection of lesions in central nervous system lymphoma (CNSL) patients before chemotherapy, during treatment and suspected CSNL recurrence, compared with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT). PROCEDURES: Twenty-six patients with newly or previously diagnosed CNSL who underwent [68 Ga]Pentixafor PET/CT were included retrospectively. Histopathological results, magnetic resonance imaging (MRI), and follow-up were used as the standard reference. The accuracy of lesion detection, maximum standardized uptake value (SUVmax) of tumors, and ratio of tumor-to-normal brain (T/N) with [68 Ga]Pentixafor PET/CT were calculated and compared to those obtained with [18F]FDG PET/CT. CXCR4 expression was analyzed through immunohistochemistry. RESULTS: Of 26 patients, 18 were newly diagnosed with a total of 23 lesions, 4 had recurrent with 4 lesions, and 4 underwent a mid-term treatment assessment after 4 cycles of chemotherapy (3 achieved complete response (CR), 1 experienced progressive disease (PD) with a total of 8 lesions). Thirty-five lesions were all clearly detected with favorable contrast by [68 Ga]Pentixafor PET/CT (accuracy, 100%), consistent with the results of contrast-enhanced magnetic resonance imaging (CE-MRI). The SUVmax of positive lesions in [68 Ga]Pentixafor PET/CT was correlated with tumor size (r = 0.555, P = 0.001). In 21 patients, compared with [18F]FDG PET/CT, [68 Ga]Pentixafor PET/CT showed a remarkably higher T/N ratio (21.93 ± 10.77 vs 4.29 ± 2.16, P = 0.000) and detected 5 more lesions in the mid-term treatment assessment of patients (P = 0.026). The CXCR4 expression of CNSL lesions was correlated with SUVmax of [68 Ga]Pentixafor PET/CT (r = 0.772, P = 0.000). CONCLUSIONS: CXCR4-directed PET/CT using [68 Ga]Pentixafor, with excellent tumor-to-background contrast, might be a more promising agent for the detection of lesions in CNSL patients than [18F]FDG PET/CT.

Characterization of the benign lesions with increased 68Ga-FAPI-04 uptake in PET/CT.

OBJECTIVES: The objective of the study was to characterize benign lesions showing increased 68Ga-FAPI-04 uptake on FAPI PET/CT. METHODS: We retrospectively reviewed 182 patients with suspected various cancers who were performed 68Ga-FAPI-04 PET/CT imaging from August 2020 to December 2020. The diagnoses of the benign lesions were made by the CT findings (CT), other imaging information (OII) (contrast enhance CT, FDG PET, ultrasound, MRI or others), clinical information (CI) (medical history, laboratory examination, symptom, physical sign and follow-up information) or histological biopsy (HB). RESULTS: A total of 185 primary malignant tumors were detected by FAPI PET/CT with the median SUVmax of 9.0 (range from 0.97 to 25.71). There were 360 benign lesions with increased FAPI uptake were detected in 146 (146/182, 80.2%) patients with the median SUVmax of 3.64 (range from 1.39 to 21.56), including inflammatory processes (n = 231, 64.2%), exostosis (n = 54, 15%), hemorrhoid (n = 47, 13.1%), fracture (n = 17, 4.7%), hepatic fibrosis (n = 4, 1.1%), and others (n = 7, 1.9%). CONCLUSION: Benign lesions with increased 68Ga-FAPI-04 uptake are common. The overall SUVmax of benign lesions is lower than that of malignant tumors, however there is a large overlap of SUVmax range. Similar to FDG PET, some benign lesions can be easily diagnosed by combining CT findings, special location and clinical data, but there are still some lesions that may be confused with malignant lesions, which need to be paid more attention. TRAIL REGISTRATION: NIH ClinicalTrials.gov (NCT04499365).

Cerebral Venous Sinus Thrombosis Caused by Neuro-Behçet Disease Accidentally Detected by 68Ga-FAPI PET/CT.

ABSTRACT: A 26-year-old man presented with recurrent oral ulcer, temporal headache, and blurred vision for 4 months. The giant cell arteritis was suspected, and 18F-FDG and 68Ga-FAPI PET/CT were done. There was no hypermetabolic lesion in 18F-FDG PET/CT. However, 68Ga-FAPI PET/CT showed multiple increased FAPI uptake lesions in the cerebral venous sinus. High-resolution MR venography revealed multiple chronic cerebral venous sinus thrombosis. Neuro-Behçet disease was diagnosed finally. This case showed 68Ga-FAPI PET/CT may play some role in the management of neuro-Behçet disease.