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.

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.

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.

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.

Identification of testicular Foxq1 as a critical modulator of lactate metabolism in mouse Sertoli cells.

Postmeiotic germ cells require the lactate produced by the adjacent Sertoli cells (SCs) as their sole energy fuels. Lactate production in SCs is elaborately regulated by monitoring the transcription of the lactate dehydrogenase A (Ldha) gene. However, the transcription factors that are responsible for the control of Ldha transcription in SCs remain ill defined. Herein, the expression of forkhead box Q1 (FOXQ1), a central modulator of glucose metabolism in liver, was demonstrated in mouse testis throughout postnatal development, with maximum levels in adult specimens. At this age, FOXQ1 was immunolocalized in the nuclei of the functionally mature SCs. Testicular levels of FOXQ1 were overtly modulated by germ cells (GCs)-derived IL-1α, in a dose- and time-dependent manner. To further clarify the biological functions of FOXQ1, we disrupted the mouse Foxq1 gene using a Cas9/RNA-mediated gene targeting strategy. Foxq1-/- males were subfertile and showed oligoasthenozoospermia due to lactate deficiency. Moreover, we provided the molecular evidence that FOXQ1 may regulate lactate production by directly targeting the transactivation of the Ldha gene in SCs. From a functional standpoint, overexpression of the exogenous Ldha ameliorated Foxq1 deficiency-impaired lactate synthesis in the SCsFoxq1-/- cells. Thus, these findings collectively underscore a reproductive facet of this recently characterized transcription factor, which may operate as a novel transcriptional integrator linking energy homeostasis and nursery function in SCs.

Fibroblast imaging of hepatic carcinoma with 68Ga-FAPI-04 PET/CT: a pilot study in patients with suspected hepatic nodules.

PURPOSE: 68Ga-FAPI-04 is a rapidly evolving PET tracer for whole-body imaging in a variety of cancers. We aimed to evaluate the diagnostic performance of 68Ga-FAPI-04 for detecting and characterizing hepatic nodules in patients with suspected carcinoma. METHODS: Twenty-five patients showing suspicious hepatic lesions for malignancy underwent 68Ga-FAPI-04 PET. The maximum and mean standardised uptake values (SUVmax, SUVmean) were measured for all detected lesions and normal hepatic tissues, respectively. The target-to-background ratio (TBR) was calculated by dividing the lesion SUVmax with the SUVmean of non-tumour liver tissue. Lesion uptake value was correlated with the in vitro hepatic FAP expression determined by immunohistochemistry (IHC). RESULTS: In total, 17 patients who underwent surgery or biopsy were recruited for the final analysis. A total of 28 intrahepatic malignant lesions were detected in 16 patients; the mean SUVmax was 8.36 ± 4.21 (range 2.21 to 15.86), and mean TBR was 13.15 ± 9.48 (range 2.79 to 38.12) in all detected lesions (n = 28). One benign patient showed negligible hepatic uptake (SUVmax = 0.47), whereas 75% of the primary intrahepatic hepatocellular carcinoma (HCC) lesions (n = 6) showed prominent FAP expression, 12.5% of the lesions (n = 1) showed moderate expression in stromal cells, and one showed negligible expression. CONCLUSIONS: 68Ga-FAPI-04 showed high sensitivity in detecting hepatic malignancies, particularly in poorly differentiated forms with concordantly elevated FAP expression.

Comparison of PET imaging of activated fibroblasts and 18F-FDG for diagnosis of primary hepatic tumours: a prospective pilot study.

PURPOSE: This study aimed to compare the performance of 68Ga-labelled fibroblast activating protein inhibitor (FAPI) PET and 18F-FDG PET for imaging of hepatic tumours. METHODS: We prospectively assessed 20 patients with suspected intrahepatic lesions. Tumour radiological features, pathology, or follow-up examinations were assessed as ground truth in correlation with PET scans. Semiquantitative analysis was additionally performed by measuring the standardised uptake value (SUV). Tumour-to-liver background ratios (TBR) were calculated and compared between 68Ga-FAPI PET and 18F-FDG PET. FAPI expression was assessed by immunochemistry in samples obtained from 7 patients with hepatocellular carcinomas (HCC)/intrahepatic cholangiocarcinoma (ICC) or granulomas. RESULTS: Primary intrahepatic tumours, including 16 HCC in 14 patients and 4 ICC in 3 patients with extrahepatic metastases, were determined by histology (n = 14) and clinical examinations (n = 3). Based on visual analysis, 17 patients presented elevated 68Ga-FAPI uptake (sensitivity: 100%, specificity: 100%), while 7 patients presented 18F-FDG avid tumours (sensitivity: 58.8%, specificity: 100%). 68Ga-FAPI PET/CT identified 17 extrahepatic metastases vs. 13 in 18F-FDG PET/CT in 2 ICC patients. Three benign liver nodules in three patients showed negligible uptake in dual-PET scans. The SUVmax_HCC = 8.47 ± 4.06 and TBRmax_HCC = 7.13 ± 5.52, and SUVmax_ICC = 14.14 ± 2.20 TBRmax_ICC = 26.46 ± 4.94 in 68Ga-FAPI-04 PET/CT were significantly higher than the 18F-FDG uptake presenting SUVmax_HCC = 4.86 ± 3.58 and TBRmax_HCC = 2.39 ± 2.21, and SUVmax_ICC = 9.19 ± 3.60 and TBRmax_ICC = 2.39 ± 2.21 (all p values < 0.05). ICC patients showed higher levels of FAPI uptake in the primary hepatic lesions compared to extrahepatic metastases, TBRmax_ICC = 15.18 ± 5.80 (p = 0.04). CONCLUSIONS: 68Ga-FAPI PET-CT has superior potential in the detection of primary hepatic malignancy compared to 18F-FDG.

Imaging CXCR4 expression in patients with suspected primary hyperaldosteronism.

PURPOSE: It is challenging to differentiate unilateral aldosterone-producing adenoma (APA) from bilateral idiopathic adrenal hyperplasia (IAH) and nonfunctional adrenal adenoma (NFA) in primary aldosteronism (PA). In a first primarily ex vivo study detection, CXC chemokine receptor type 4 (CXCR4) expression has been shown to be a valuable tool for the detection of APA. In this study, we aimed to clinically evaluate CXCR4 imaging with 68Ga-pentixafor PET/CT for detecting APA. METHODS: We prospectively recruited 36 patients with clinical suspicion of PA. All patients underwent 68Ga-pentixafor PET/CT. Positive lesions were defined based on higher tracer uptake in adrenal nodular(s) shown on CT than the normal adrenal. These lesions were referred for adrenalectomy subsequently. All patients received clinical follow-up. Semi-quantitative analysis using maximum standardized uptake value (SUVmax), lesion-to-liver ratio (LLR), and lesion-to-contralateral ratio (LCR) has also been performed. PET/CT results were correlated with clinical presentation and follow-up. RESULTS: Thirty-nine adrenal lesions in 36 patients were found; 25 APA, 4 IAH, and 10 NFA according to histopathology and clinical assessment. Sensitivity, specificity, and accuracy of 68Ga-pentixafor PET/CT in distinguishing APA by visualization were 100%, 78.6%, and 92.3% respectively. The SUVmax of APA (21.34 ± 9.41, n = 25) was significantly higher than that of non-APA lesions (6.29 ± 2.10, n = 14, P < 0.0001). An optimal threshold of SUVmax = 11.18 was determined for predicting APA with a sensitivity of 88.0%, specificity of 100%, and an accuracy of 92.3%. A cutoff value for LCR of 2.12 yielded a sensitivity of 100% and a specificity of 92.9%, whereas a cutoff value for LLR of 2.36 reached at both 100% of sensitivity and specificity. All patients with (removed) positive lesions benefited from surgery. CONCLUSION: 68Ga-Pentixafor PET/CT may be used to non-invasively detect APA in PA patients.

A concisely automated synthesis of TSPO radiotracer [18 F]FDPA based on spirocyclic iodonium ylide method and validation for human use.

Fluorine-18 labeled N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide ([18 F]FDPA) is a potent and selective radiotracer for positron-emission tomography (PET) imaging of the translocator protein 18 kDa (TSPO). Our previous in vitro and in vivo evaluations have proven that this tracer is promising for further human translation. Our study addresses the need to streamline the automatic synthesis of this radiotracer to make it more accessible for widespread clinical evaluation and application. Here, we successfully demonstrate a one-step radiolabeling of [18 F]FDPA based on a novel spirocyclic iodonium ylide (SCIDY) precursor using tetra-n-butyl ammonium methanesulfonate (TBAOMs), which has demonstrated the highest radiochemical yields and molar activity from readily available [18 F]fluoride ion. The nucleophilic radiofluorination was completed on a GE TRACERlab FX2 N synthesis module, and the formulated [18 F]FDPA was obtained in nondecay corrected (n.d.c) radiochemical yields of 15.6 ± 4.2%, with molar activities of 529.2 ± 22.5 GBq/µmol (14.3 ± 0.6 Ci/µmol) at the end of synthesis (60 minutes, n = 3) and validated for human use. This methodology facilitates efficient synthesis of [18 F]FDPA in a commercially available synthesis module, which would be broadly applicable for routine production and widespread clinical PET imaging studies.

Preclinical evaluation of a dual sstr2 and integrin αvß3-targeted heterodimer [68Ga]-NOTA-3PEG4-TATE-RGD.

PURPOSE: Multiple receptors are co-expressed in many types of cancers. Octreotate (TATE) and Arg-Gly-Asp (RGD) peptides target somatostatin receptor 2 (sstr2) and integrin αvß3, respectively. We developed and synthesized a heterodimer NOTA-3PEG4-TATE-RGD (3PTATE-RGD) and aimed to investigate its characteristics for dual-targeting sstr2 and integrin αvß3. METHODS: TATE and RGD peptides and 1,4,7-triazacylononane-N',N'',N'''-triacetic acid (NOTA) were linked through a glutamate and polyethylene glycol (PEG) linker, then 3PTATE-RGD was labeled with 68Ga ion. Receptor-binding characteristics and tumor-targeting efficacy were tested in vitro and in vivo using H69 and A549 lung cancer cell lines and tumor-bearing mice models. RESULTS: [68Ga]-3PTATE-RGD had comparable sstr2 and integrin αvß3-binding affinity with monomeric TATE and RGD in cell uptake and PET imaging study, respectively. In the competition study, H69 and A549 tumor uptake of [68Ga]-3PTATE-RGD was completed inhibited in the presence of an excess amount of unlabeled TATE or RGD, respectively. The blocked level didn't grow when both of TATE and RGD mixture was co-injected with [68Ga]-3PTATE-RGD. The pharmacokinetics of [68Ga]-3PTATE-RGD is comparable with [68Ga]-TATE and [68Ga]-RGD, resulting in a larger application. CONCLUSION: [68Ga]-3PTATE-RGD showed improved and wider tumor-targeting efficacy compared with monomeric TATE and RGD peptides, which warrants its further investigation in detection both of sstr2 and integrin αvß3-related carcinomas.

Semi-automatic synthesis and biodistribution of N-(2-18F-fluoropropionyl)-bis(zinc (II)-dipicolylamine) (18F-FP-DPAZn2) for AD model imaging.

BACKGROUND: Phosphatidylserine (PS)-targeting positron emission tomography (PET) imaging with labeled small-molecule tracer is a crucial non-invasive molecule imaging method of apoptosis. In this study, semi-automatic radiosynthesis and biodistribution of N-(2-18F-fluoropropionyl)-bis(zinc(II)-dipicolylamine) (18F-FP-DPAZn2), as a potential small-molecule tracer for PET imaging of cell death in Alzheimer's disease (AD) model, were performed. METHODS: 18F-FP-DPAZn2 was synthesized on the modified PET-MF-2V-IT-I synthesizer. Biodistribution was determined in normal mice and PET images of AD model were obtained on a micro PET-CT scanner. RESULTS: With the modified synthesizer, the total decay-corrected radiochemical yield of 18F-FP-DPAZn2 was 35 ± 6% (n = 5) from 18F- within 105 ± 10 min. Biodistribution results showed that kidney has the highest uptake of 18F-FP-DPAZn2. The uptake of radioactivity in brain kept at a relatively low level during the whole observed time. In vivo 18F-FP-DPAZn2 PET images demonstrated more accumulation of radioactivity in the brain of AD model mice than that in the brain of normal mice. CONCLUSIONS: The semi-automatic synthetic method provides a slightly higher radiochemical yield and shorter whole synthesis time of 18F-FP-DPAZn2 than the manual operation method. This improved method can give enough radioactivity and high radiochemical purity of 18F-FP-DPAZn2 for in vivo PET imaging. The results show that 18F-FP-DPAZn2 seems to be a potential cell death tracer for AD imaging.

Positron emission tomography imaging of cell death with [(18)F]FPDuramycin.

The noninvasive imaging of cell death, including apoptosis and necrosis, is an important tool for the assessment of degenerative diseases and in the monitoring of tumor treatments. Duramycin is a peptide of 19-amino acids. It binds specifically to phosphatidylethanolamine a novel molecular target for cell death. N-(2-(18)F-Fluoropropionyl)duramycin ([(18)F]FPDuramycin) was prepared as a novel positron emission tomography (PET) tracer from the reaction of duramycin with 4-nitrophenyl 2-[(18)F]fluoropropionate ([(18)F]NFP). Compared with control cells (viable tumor cells), the in vitro binding of [(18)F]FPDuramycin with apoptotic cells induced by anti-Fas antibody resulted in a doubling increase, while the binding of [(18)F]FPDuramycin with necrotic cells induced by three freeze and thaw cycles resulted in a threefold increase. Biodistribution study in mice exhibited its rapid blood and renal clearance and predominant accumulation in liver and spleen over 120 min postinjection. Small-animal PET/CT imaging with [(18)F]FPDuramycin proved to be a successful way to visualize in vivo therapeutic-induced tumor cell death. In summary, [(18)F]FPDuramycin seems to be a potential PET probe candidate for noninvasive visualization of in vivo cell death sites induced by chemotherapy in tumors.

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.

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.

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.