68Ga-Pentixafor PET/CT for Imaging of Chemokine Receptor 4 Expression in Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma: Comparison to 18F-FDG PET/CT.
ABSTRACT: 18F-FDG PET/CT has some limitations in the evaluation of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL), an indolent B-cell lymphoma that primarily involves the bone marrow. Because there is a high level of chemokine receptor 4 expression in the B cells of WM/LPL patients, we performed a prospective cohort study to evaluate the performance of 68Ga-pentixafor, which targets chemokine receptor 4 in WM/LPL, and to compare it with the performance of 18F-FDG. Methods: Seventeen patients with WM/LPL were recruited. All patients underwent both 68Ga-pentixafor PET/CT and 18F-FDG PET/CT. A positive PET/CT result was defined as the presence of focal lesions with positive PET results or diffuse bone marrow patterns (uptake > liver). The rates of positive results for PET/CT scans of bone marrow, lymph nodes, and other extramedullary involvement were statistically compared. Results:68Ga-pentixafor PET/CT had a higher rate of positive results than 18F-FDG PET/CT (100% vs. 58.8%; P = 0.023) in the recruited WM/LPL patients. The sensitivities of 68Ga-pentixafor PET/CT and 18F-FDG PET/CT for detecting bone marrow involvement were 94.1% and 58.8%, respectively (P = 0.077). In terms of detecting lymph node involvement, 68Ga-pentixafor PET/CT had a significantly higher rate of positive results than 18F-FDG PET/CT (76.5% vs. 11.8%; P = 0.003). In addition, 68Ga-pentixafor detected more paramedullary and central nervous system involvement than 18F-FDG. Conclusion:68Ga-pentixafor might be a promising imaging agent for the assessment of WM/LPL.
Project description:<h4>Purpose</h4> 68Ga-pentixafor PET/CT was reported to have a high sensitivity in detecting tumor involvement of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) in our previous study. We aimed to further investigate the semi-quantitative measurements of 68Ga-pentixafor PET/CT in response assessment in WM/LPL. <h4>Methods</h4> Fifteen patients with WM/LPL were recruited in a prospective cohort study and underwent both 68Ga-pentixafor and 18F-FDG PET/CT at baseline and post-treatment. PET/CT-based responses were analyzed with semi-quantitative assessments of metabolic tumor volume (MTV) and total lesions glycolysis/uptake (TLGFDG and TLUCXCR4), and the correlation between PET/CT-based response and clinical response, monoclonal protein and IgM response was analyzed. <h4>Results</h4> After chemotherapy, 5 patients had complete response or very good partial response, 8 had partial response or minimal response and 2 had progressive disease. In quantitative analysis, 68Ga-pentixafor PET/CT-based response (measured in ∆TLUCXCR4%, ∆MTVCXCR4%, ∆SUVpeak%) showed a significant direct correlation with clinical response, monoclonal protein and IgM response (p < 0.01). However, 18F-FDG PET/CT-based response was independent from clinical response (p > 0.05). <h4>Conclusions</h4> The semi-quantitative measurements of 68Ga-pentixafor PET/CT outperformed 18F-FDG PET/CT in response assessment of WM/LPL. <h4>Supplementary Information</h4> The online version contains supplementary material available at 10.1186/s13550-021-00852-0.
Project description:Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand (68)Ga-Pentixafor. 15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent (68)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUVmax, SUVmean). Tumor-to-background ratios (TBR) were calculated for both PET probes. (68)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples. (68)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUVmean and SUVmax of 3.0±1.5 and 3.9±2.0 respectively. Respective values for (18)F-FET were 4.4±2.0 (SUVmean) and 5.3±2.3 (SUVmax). TBR for SUVmean and SUVmax were higher for (68)Ga-Pentixafor than for (18)F-FET (SUVmean 154.0±90.7 vs. 4.1±1.3; SUVmax 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high (68)Ga-Pentixafor uptake; regions of the same tumor without apparent (68)Ga-Pentixafor uptake showed no or low receptor expression. In this pilot study, (68)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, (68)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.
Project description:<h4>Aim/purpose</h4>Fibroblast activation protein-(FAP)-ligands, a novel class of tracers for PET/CT imaging, demonstrated promising results in previous studies in various malignancies compared to standard [<sup>18</sup>F]FDG PET/CT. <sup>68</sup>Ga-labeled fibroblast activation protein inhibitor-([<sup>68</sup>Ga]Ga-DOTA-FAPI)-PET/CT impresses with sharp contrasts in terms of high tumor uptake and low background noise leading to clear delineation. [<sup>18</sup>F]FDG PET/CT has limited accuracy in bladder cancer due to high background signal. Therefore, we sought to evaluate the diagnostic potential of [<sup>68</sup>Ga]FAPI in patients with bladder cancer.<h4>Material and methods</h4>This retrospective analysis consisted of 8 patients (median age 66), 7 of whom underwent both [<sup>68</sup>Ga]FAPI and [<sup>18</sup>F]FDG PET/CT scans with a median time interval of 5 days (range 1-20 days). Quantification of tracer uptake was determined with SUV<sub>max</sub> and SUV<sub>mean</sub>. Furthermore, the tumor-to-background ratio (TBR) was derived by dividing the SUV<sub>max</sub> of tumor lesions by the SUV<sub>max</sub> of adipose tissue, skeletal muscle, and blood pool.<h4>Results</h4>Overall, 31 metastases were detected in five patients including lymph node metastases (n = 23), bone metastases (n = 4), lung metastases (n = 3), and a peritoneal metastasis (n = 1). In one patient, [<sup>68</sup>Ga]FAPI demonstrated significant uptake in the primary tumor located in the bladder wall. [<sup>68</sup>Ga]FAPI-PET/CT demonstrated significantly higher uptake compared to [<sup>18</sup>F]FDG PET/CT with higher mean SUV<sub>max</sub> (8.2 vs. 4.6; p = 0.01). Furthermore, [<sup>68</sup>Ga]FAPI detected additional 30% (n = 9) lesions, missed by [<sup>18</sup>F]FDG. TBR demonstrated favorable uptake for [<sup>68</sup>Ga]FAPI in comparison to [<sup>18</sup>F]FDG. Significant differences were determined with regard to metastasis/blood pool ([<sup>68</sup>Ga]FAPI 5.3 vs [<sup>18</sup>F]FDG 1.9; p = 0.001).<h4>Conclusion</h4>[<sup>68</sup>Ga]FAPI-PET/CT is a promising diagnostic radioligand for patients with bladder cancer. This first described analysis of FAP-ligand in bladder cancer revealed superiority over [<sup>18</sup>F]FDG in a small patient cohort. Thus, this so far assumed potential has to be confirmed and extended by larger and prospective studies.
Project description:<h4>Purpose</h4>FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of <sup>68</sup>Ga-FAPI versus standard-of-care <sup>18</sup>F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers.<h4>Material and methods</h4>This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both <sup>68</sup>Ga-FAPI and <sup>18</sup>F-FDG PET/CT within a median time interval of 10 days (range 1-89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ).<h4>Results</h4>A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. <sup>68</sup>Ga-FAPI uptake in primary tumors and metastases was comparable to <sup>18</sup>F-FDG in most cases. The SUVmax was significantly lower for <sup>68</sup>Ga-FAPI than <sup>18</sup>F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, <sup>68</sup>Ga-FAPI TBRs were significantly higher than <sup>18</sup>F-FDG TBRs in some sites, including liver and bone metastases.<h4>Conclusion</h4>Quantitative tumor uptake is comparable between <sup>68</sup>Ga-FAPI and <sup>18</sup>F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for <sup>68</sup>Ga-FAPI. Thus, <sup>68</sup>Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological <sup>18</sup>F-FDG uptake.
Project description:CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination and poor prognosis. We evaluated the novel CXCR4 probe [(68)Ga]Pentixafor for in vivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [(68)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [(68)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [(18)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34(+) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [(68)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases.
Project description:Several studies have demonstrated an expression of the prostate-specific membrane antigen (PSMA) in the cancer-related neovasculature of thyroid malignancies. Due to the poor prognosis and limited therapeutic options for patients with anaplastic (ATC) and poorly differentiated (PDTC) thyroid carcinoma, the aim of our study was to investigate the theranostic approach of PSMA expression in these patients. The PSMA uptake on Gallium-68 (<sup>68</sup>Ga)-PSMA-positron emission tomography/computed tomography (PET/CT) and glucose uptake on F-18-Fluordeoxyglucose (<sup>18</sup>F-FDG)-PET/CTs were analysed in two ATC and six PDTC patients. The PSMA expression in corresponding patients' tissue samples was detected by immunohistochemistry. In addition, various tissue sections from 22 ATC and six PDTC patients were examined concerning PSMA expression. <sup>68</sup>Ga-PSMA-PET/CT showed heterogeneous PSMA expression among patients and lesions. Six of the eight analyzed patients (two ATC, four PDTC) showed increased glucose metabolism without increased PSMA uptake after PET/CT. In one patient (PDTC), <sup>18</sup>F-FDG-PET/CT tracer uptake was positive and <sup>68</sup>Ga-PSMA-PET/CT showed heterogeneous results. Another patient (PDTC) evidenced only PSMA-positive lesions and received two cycles of Lutetium-177 (<sup>177</sup>Lu)-PSMA therapy, which kept his disease stable for seven months. There was a correlation between immunohistochemical PSMA expression and uptake on <sup>68</sup>Ga-PMSA-PET/CT in three of the examined patients. Twenty-seven of the analyzed 39 ATC and 13 of the analyzed 22 PDTC tissue sections showed a strong PSMA expression. Considering the rarity of PDTC and ATC, which is the reason for the small patient population we studied, the findings of this study confirm the high diagnostic sensitivity and superiority of <sup>18</sup>F-FDG-PET/CT in comparison to <sup>68</sup>Ga-PSMA-PET/CT in the diagnosis of ATC and PDTC. However, it can be suggested that <sup>68</sup>Ga-PMSA-PET/CT can be considered as a beneficial adjunct to the well-established <sup>18</sup>F-FDG-PET/CT for a few individual selected patients with ATC and PDTC to detect lesions not discovered by <sup>18</sup>F-FDG-PET/CT and to determine patients' eligibility for a radioligand therapy. Radiolabelled PSMA-ligands may, in the future, represent a theranostic approach with only minor side effects for a few individual selected patients with ATC and PDTC who need alternative treatment options in case of progression when established therapies are no longer effective. However, due to the small sample size of our collective, larger studies are needed to allow for a final evaluation on the significance of PSMA-targeted diagnostic and therapy for ATC and PDTC.
Project description:<h4>Background</h4>Expression of CXCR4, a chemokine (C-X-C motif) receptor that plays a central role in tumor growth and metastasis of circulating tumor cells, has been described in a variety of solid tumors. A high expression of CXCR4 has a prognostic significance with regard to overall and progression-free survival and offers a starting point for targeted therapies. In this context, Ga-Pentixafor-Positron Emission Tomography/Computer Tomography (PET/CT) offers promising possibility of imaging the CXCR4 expression profile. We set out to compare a [18F] fluorodeoxyglucose (FDG)-PET/CT and a [68Ga]Pentixafor-PET/CT in (re-)staging and radiation planning of patients with localized esophageal cancer.<h4>Materials and methods</h4>In this retrospective analysis, ten patients, with adeno- or squamous cell carcinoma of the esophagus (n =?3 and n =?7, respectively), which were scheduled for radio (chemo) therapy, were imaged using both Pentixafor and FDG PET/CT examinations. All lesions were visually rated as Pentixafor and FDG positive or negative. For both tracers, SUVmax was measured all lesions and compared to background. Additionally, immunohistochemistry of CXCR4 was obtained in patients undergoing surgery.<h4>Results</h4>FDG-positive tumor-suspicious lesions were detected in all patients and a total of 26 lesions were counted. The lesion-based analysis brought equal status in 14 lesions which were positive for both tracers while five lesions were FDG positive and Pentixafor negative and seven lesions were FDG negative, but Pentixafor positive. Histopathologic correlation was available in seven patients. The CXCR4 expression of four non-pretreated tumour lesion samples was confirmed immunohistochemically.<h4>Conclusion</h4>Our data shows that additional PET/CT imaging with Pentixafor for imaging the CXCR4 chemokine receptor is feasible but heterogeneous in both newly diagnosed and pretreated recurrent esophageal cancer. In addition, the Pentixafor PET/CT may serve as complementary tool for radiation field expansion in radiooncology.
Project description:UNLABELLED:This study was designed to assess the diagnostic value of (68)Ga-NOTA-PRGD2 (NOTA-PRGD2 is NOTA-PEG4-E[c(RGDfK)]2) PET/CT in lung cancer. METHODS:Ninety-one patients (48 men and 43 women; age, 22-82 y) with suspected lung lesions on CT were enrolled with informed consent. Immediately after intravenous injection of 117.7 ± 37.7 MBq of (68)Ga-NOTA-PRGD2, 15 patients underwent dynamic whole-body PET/CT scans for 1-2 h, and the remaining 76 patients underwent whole-body PET/CT scans at 30 ± 10 min after bolus injection. Each patient also underwent standard (18)F-FDG PET/CT for comparison. RESULTS:No side effect was found after (68)Ga-NOTA-PRGD2 injection. (68)Ga-NOTA-PRGD2 was rapidly cleared from the blood pool and primarily excreted through the urinary system. The standardized uptake values of proven malignancies were significantly higher than those of the benign ones. With an average standardized uptake value of greater than 1.3 being considered malignant, the sensitivity, specificity, and accuracy of (68)Ga-NOTA-PRGD2 PET/CT in diagnosing lung cancer were 83.8% (57/68), 91.3% (21/23), and 85.7% (78/91), respectively. The diagnostic value of (68)Ga-NOTA-PRGD2 for lung cancer is comparable to that of (18)F-FDG PET/CT. However, (68)Ga-NOTA-PRGD2 PET/CT is more specific than (18)F-FDG PET/CT in assessing lymph node metastasis, with positive and negative predictive values of 90.0% (27/30) and 93.8% (121/129), respectively, whereas those of (18)F-FDG PET/CT were 30.2% (29/96) and 90.5% (57/63), respectively. CONCLUSION:This study indicates the efficacy of (68)Ga-NOTA-PRGD2 PET/CT in lung cancer diagnosis. (68)Ga-NOTA-PRGD2 PET/CT shows significant advantage over (18)F-FDG PET/CT in judging metastatic lymph nodes with higher specificity.
Project description:<h4>Background</h4>Differentiated thyroid carcinoma (DTC) is the most common type of thyroid cancer. Treatment with surgery, radioactive iodine (RAI), and TSH suppression is effective in most patients. Five to 15% of patients become RAI refractory and need alternative therapy; however, treatment options are limited. <sup>68</sup>Ga-PSMA PET/CT, originally developed for prostate cancer, is also applicable to other malignancies, including thyroid carcinoma. The uptake of PSMA in thyroid carcinoma gives opportunities for imaging and therapy of RAI-refractory DTC. The aim of this study was to analyze imaging on <sup>68</sup>Ga-PSMA PET/CT and evaluate the response to <sup>177</sup>Lu-PSMA-617 therapy in patients with RAI-refractory DTC.<h4>Materials and methods</h4>Five patients with RAI-refractory DTC underwent <sup>68</sup>Ga-PSMA PET/CT to determine their eligibility for <sup>177</sup>Lu-PSMA-617 therapy. <sup>68</sup>Ga-PSMA PET/CTs were analyzed visually and quantitatively. Response to <sup>177</sup>Lu-PSMA-617 therapy was evaluated using imaging and thyroglobulin (Tg) values.<h4>Results</h4>Tracer uptake suspicious for distant metastases was depicted in all <sup>68</sup>Ga-PSMA PET/CTs. Based on tracer uptake, three patients were eligible for <sup>177</sup>Lu-PSMA-617 therapy, of whom two were treated. One patient showed disease progression on imaging 1 month later, while her Tg values gradually increased from 18 to 63 μg/L in the months after treatment. Another patient showed partial, temporary response of lung and liver metastases. Her Tg levels initially decreased from 17 to 9 μg/L. However, 7 months after treatment, there was disease progression on imaging and Tg levels had increased to 14 μg/L. Imaging with <sup>68</sup>Ga-PSMA PET/CT could be compared to <sup>18</sup>FDG PET/CT in three patients. Two patients showed additional lesions on <sup>68</sup>Ga-PSMA PET/CT, and one patient showed concordant imaging.<h4>Conclusion</h4><sup>68</sup>Ga-PSMA PET/CT appears to have added value in patients with RAI-refractory DTC, as it is able to detect various types of lesions, some of which were not picked up by <sup>18</sup>FDG PET/CT. Furthermore, <sup>68</sup>Ga-PSMA PET/CT might be used to identify patients eligible for treatment with <sup>177</sup>Lu-PSMA-617. One of the two patients who underwent <sup>177</sup>Lu-PSMA-617 therapy showed a modest, temporary response. To draw conclusions about the effectiveness of this therapy, more research is needed.
Project description:<h4>Background</h4>This is a pilot study of radiomics based on <sup>68</sup>Ga-NOTA-PRGD2 [NOTA-PEG4-E[c(RGDfK)]2)] and <sup>18</sup>F-FDG PET/CT to (i) evaluate the diagnostic efficacy of radiomics features of <sup>68</sup>Ga-NOTA-PRGD2 PET in the differential diagnosis of benign and malignant pulmonary space-occupying lesions and (ii) compare the diagnostic efficacy of multi-modality and multi-probe images.<h4>Methods</h4>We utilized a dataset of 48 patients who participated in <sup>68</sup>Ga-NOTA-PRGD2 PET/CT and <sup>18</sup>F-FDG PET/CT clinical trials to extract image features and evaluate their diagnostic efficacy in the differentiation of benign and malignant lesions by the Mann-Whitney U test. After feature selection with sequential forward selection, random forest models were developed with tenfold cross-validation. The diagnostic performance of models based on different image features was visualized by receiver operating characteristic (ROC) curves and compared by permutation tests.<h4>Results</h4>Fourteen of the <sup>68</sup>Ga-NOTA-PRGD2 PET features between benign and malignant pulmonary space-occupying lesions had significant differences (P<0.05, Mann-Whitney U test). Eighteen of the <sup>68</sup>Ga-NOTA-PRGD2 PET features demonstrated higher AUC values than all CT features in the differential diagnosis of pulmonary lesions. The AUC value (0.908) of the three-modal feature model was significantly higher (P<0.05, permutation test) than those of the single- and dual-modal models.<h4>Conclusion</h4><sup>68</sup>Ga-NOTA-PRGD2 PET features have better diagnostic capacity than CT features for pulmonary space-occupying lesions. The combination of multi-modality and multi-probe images can improve the diagnostic efficiency of models. Our preliminary clinical hypothesis of using radiomics based on <sup>68</sup>Ga-NOTA-PRGD2 PET images and multimodal images as a diagnostic tool warrants further validation in a larger multicenter sample size.