Mean SUVmax Research Articles

SVCT2-targeted PET imaging agent for the evaluation of LN metastasis of thyroid cancer.

Cervical lymph node (LN) metastasis is highly prevalent in thyroid cancer (TC). However, the lack of diagnostic modalities that enable real-time assessment of LN metastasis remains a challenge in providing efficient clinical decision-making and optimal patient care. Sodium-ascorbate co-transporters (SVCTs) have shown high expression levels in TC, presenting a potential target for visualizing LN metastasis. In this study, we successfully prepared [18F]FAA, targeting SVCT2, with high radiochemical yield. Subsequently, we demonstrated a significantly high expression of SVCT2 in LN metastasis compared to normal tissues. Then, we demonstrated that [18F]FAA exhibited a significant and specific uptake in TC cells expressing SVCT2. Biodistribution and micro-PET/CT imaging in tumor and lymphadenitis model mice indicated significant [18F]FAA uptake in tumors but not in regions of LN inflammation. Preliminary clinical investigations revealed that [18F]FAA detected a greater number of LN metastatic lesions with higher mean SUVmax and tumor-to-background ratio (TBR) than [18F]FDG. These results highlight the potential of [18F]FAA as a non-invasive imaging agent for accurately detecting LN metastasis in TC.

18F−Prostate−Specific Membrane Antigen PET/CT imaging for potentially resectable pancreatic cancer (PANSCAN−2): a phase I/II study

BackgroundCurrent diagnostic imaging modalities have limited ability to differentiate between malignant and benign pancreaticobiliary disease, and lack accuracy in detecting lymph node metastases. 18F-Prostate-Specific Membrane Antigen (PSMA) PET/CT is an imaging modality used for staging of prostate cancer, but has incidentally also identified PSMA-avid pancreatic lesions, histologically characterized as pancreatic ductal adenocarcinoma (PDAC). This phase I/II study aimed to assess the feasibility of 18F-PSMA PET/CT to detect PDAC.MethodsSeventeen patients with clinically resectable PDAC underwent 18F-PSMA PET/CT prior to surgical resection. Images were analyzed both visually and (semi)quantitatively by deriving the maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR). TBR was defined as the ratio between SUVmax of the primary tumor divided by SUVmax of the aortic blood pool. Finally, tracer uptake on PET was correlated to tissue expression of PSMA in surgical specimens.ResultsOut of 17 PSMA PET/CT scans, 13 scans demonstrated positive PSMA tracer uptake, with a mean SUVmax of 5.0 ± 1.3. The suspected primary tumor was detectable (TBR ≥ 2) with a mean TBR of 3.3 ± 1.3. For histologically confirmed PDAC, mean SUVmax and mean TBR were 4.9 ± 1.2 and 3.3 ± 1.5, respectively. Although eight patients had histologically confirmed regional lymph node metastases and two patients had distant metastases, none of these metastases demonstrated 18F-PSMA uptake. There was no correlation between 18F-PSMA PET/CT SUVmax and tissue expression of PSMA in surgical specimens.Conclusions18F-PSMA PET/CT was able to detect several pancreaticobiliary cancers, including PDAC. However, uptake was generally low, not specific to PDAC and no tracer uptake was observed in lymph node or distant metastases. The added value of PSMA PET in this setting appears to be limited.Trial registrationThe trial is registered as PANSCAN-2 in the European Clinical Trials Database (EudraCT number: 2020–002185-14).Graphical

Prognostic and Predictive Values of F-18 FDG PET/CT Volumetric Parameters in Small Cell Lung Cancer

Introduction: Volumetric parameters of the 18F-FDG PET/CT can contribute to the treatment decision in high risk patients. In the present study, we aimed to examine the predictive, prognostic, and clinical value of PET/CT by using the two volumetric parameters: metabolic tumor volume (MTV) and total lesion glycolysis (TLG), SUVmax to concurrently evaluate survival data in patients diagnosed with small cell lung cancer (SCLC). Methods: 244 patients with SCLC, who underwent 18F-FDG PET/CT imaging for staging purpose were enrolled. Primary tumor SUVmax, MTV (40-70%) and TLG (40-70%) obtained from PET/CT were documented. Results: All lesions (n=244) showed 18F-FDG uptake, mean SUVmax of 19.74±8.71 [range (min – max) = 3.80 - 58.80]. SUVmax was significantly higher in tumors with diameters > 2 cm compared to those with diameters ≤ 2 cm (p=0.000). The mean survival time was significantly shorter in patients with tumor diameter greater than 2 cm, locoregional LN involvement, distant nodal metastasis, or distant organ metastasis (p=0.019, p

F-18 FDG PET/CT based Preoperative Machine Learning Prediction Models for Evaluating Regional Lymph Node Metastasis Status of Patients with Colon Cancer.

This study aimed to develop a simple machine-learning model incorporating lymph node metastasis status with F-18 Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and clinical information for predicting regional lymph node metastasis in patients with colon cancer. This retrospective study included 193 patients diagnosed with colon cancer between January 2014 and December 2017. All patients underwent F-18 FDG PET/CT and blood test before surgery. One categorical variable (lymph node FDG uptake [LNFDG]) and six continuous variables (age, neutrophil-to-lymphocyte ratio [NLR], carcinoembryonic antigen [CEA], carbohydrate antigen 19-9 [CA19-9], C-reactive protein, and maximal standardized uptake value (SUVmax) of the primary tumor) were used as input variables. Four supervised machine learning methods were used to build predictive models: logistic regression (LR), random forest (RF), gradient boosting machine (GBM), and support vector machine (SVM). Area under the receiver operating characteristic curve (AUC) of the validation set were used for evaluating and comparing model performance. The number of patients with lymph node metastasis were 63 (33%). The mean number of harvested lymph nodes was 28.8 ± 11.4. The mean CEA, CA19-9, and CRP levels were 4.8 ± 9.3 ng/ml, 15.6 ± 42.8 U/ml, and 1.0 ± 3.0 mg/dl, respectively. The mean NLR was 2.2 ± 1.2. The mean SUVmax levels of the primary tumor were 15.2 ± 7.9. Fifty-one (26%) patients showed FDG uptake in the pericolic lymph nodes. The mean AUC of the LR, RF, GBM, and SVM methods for the LNFDG model was 0.7046, 0.7047, 0.7040, and 0.7058, respectively. The mean AUC of the LR, RF, GBM, and SVM methods for the LNFDG plus clinical information model was 0.7046, 0.7302, 0.7444, and 0.7097, respectively. Machine learning methods using LNFDG and clinical information could predict the lymph node metastasis status in patients with colon cancer with higher accuracy than a model using only FDG uptake of the lymph nodes.

Imaging of unicentric hyaline-vascular variant of Castleman disease: Emphasis on perilesional fat stranding and fatty proliferation.

The hyaline-vascular variant of Castleman disease (HVCD) is relatively uncommon and demonstrates no specific clinical or laboratory findings; therefore, its preoperative diagnosis warrants a radiological evaluation. This study aimed to review imaging findings of HVCD, focusing on perilesional fat stranding and fatty proliferation. Patients with a pathologically confirmed HVCD diagnosis who had undergone CT were recruited from five hospitals from January 2000 to March 2023. Three experienced radiologists assessed CT findings, including lesion location, lesion size, calcification, enhanced pattern, feeding vessel visualization, and arterial enhancement. Perilesional fat stranding, fatty proliferation, neighboring fascial thickening, and surrounding lymphadenopathy were the primary targets of analysis. Moreover, the intensities and apparent diffusion coefficient (ADC) values on MRI and the maximum standardized uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography (PET) were evaluated. This study enrolled 43 patients (mean age 41.3 years ± 14.6 [standard deviation], 23 women). All lesions were well-defined round masses. Calcification and feeding vessels were detected in 21% (9/43) and 86% (36/43) of the patients, respectively. Perilesional fat stranding and fatty proliferation were observed in 44% (19/43) and 19% (8/43), respectively, with fatty proliferation detected only in retroperitoneal HVCD. Neighboring fascial thickening and surrounding lymphadenopathy were identified in 21% and 60%, respectively. The mean ADC value and SUVmax were 0.884 × 10-3 mm2/s and 5.0, respectively. Retroperitoneal HVCD cases with perilesional fatty proliferation demonstrated a higher visceral fat ratio than those without (p = 0.046). Perilesional fat stranding and fatty proliferation were new characteristics of HVCD, especially in retroperitoneal cases.

Dual-Time Point 68Ga-FAPI-04 PET/CT Improves Tumor Delineation and Cervical Lymph Node Metastasis Identification in Patients With Head and Neck Squamous Cell Carcinoma.

The purpose of this study was to evaluate the benefit of dual-time point 68Ga-FAPI-04 PET/CT in staging head and neck squamous cell carcinoma (HNSCC). Sixty-nine treatment-naive patients with HNSCC were enrolled. Each patient underwent whole-body 68Ga-FAPI-04 PET/CT at approximately 30 minutes postinjection and a delayed scan in head and neck region at 2 hours. Radiotracer uptake (SUVmax), tumor-to-background ratio, change in SUVmax (∆SUVmax), retention index, diagnostic performance, and staging were explored. Histopathology was the reference standard. Primary tumors showed similar average SUVmax between early (17.89) and delayed scans (17.86, P = 0.241). However, the tumor-to-background ratios of delayed imaging were all significantly higher than those of early imaging (all P < 0.001). In 38 patients who underwent neck dissection, metastatic lymph nodes showed higher mean SUVmax on delayed imaging than on early imaging (early 10.53 ± 5.98 vs delayed 11.71 ± 6.36, P < 0.001), whereas nonmetastatic lymph nodes showed the opposite result (early 3.51 ± 0.51 vs delayed 2.58 ± 0.63, P = 0.002). The mean ∆SUVmax and retention index of metastatic and nonmetastatic lymph nodes were 1.19 versus -0.93 and 12.79% versus -26.55%, respectively. N staging was correctly altered in 3 (3/38) patients based on delayed images. Delayed 68Ga-FAPI-04 PET/CT can effectively acquire high-contrast images, better tumor delineation, and detect hidden lesions near or within the tissues influenced by physiological uptake for HNSCC. In addition, dual-time point imaging adds diagnostic value for the differentiation of metastatic from nonmetastatic lymph nodes.

18F]Fluorthanatrace PET in Ovarian Cancer: Comparison with [18F]FDG PET, Lesion Location, Tumor Grade, and Breast Cancer Gene Mutation Status.

Poly(adenosine diphosphate-ribose) polymerase-1 (PARP1) inhibitors have improved ovarian cancer treatment outcomes. However, clinical response remains heterogeneous. Existing biomarkers, mainly breast cancer susceptibility genes 1 and 2 (BRCA1/2), are suboptimal. New tools are needed to guide patient selection. In this study, [18F]fluorthanatrace ([18F]FTT), a PET radiotracer for imaging PARP1, was compared with [18F]FDG and tumor features commonly assessed in ovarian cancer. Methods: Subjects with epithelial ovarian cancer underwent both [18F]FTT and [18F]FDG PET before new oncologic treatment. The SUVmax of [18F]FTT and [18F]FDG was compared between lesions. [18F]FTT SUVmax was compared with tumor location, tumor grade, and germline or somatic BRCA1/2 status. Linear mixed models were fitted to identify subject-level differences. Results: Fifty-five lesions were identified in 14 subjects. No correlation was found between [18F]FTT SUVmax and [18F]FDG SUVmax per lesion, supporting distinct molecular targets. [18F]FTT uptake varied widely across lesions, with no significant differences between mean SUVmax and tumor location, grade, or BRCA1/2 status. Conclusion: Our findings suggest that [18F]FTT PET may provide unique information on ovarian cancer distinct from [18F]FDG PET and commonly assessed tumor features. Our results imply a wide range of PARP1 expression in the studied ovarian tumors not explained by [18F]FDG PET, location, grade, or mutational status.

Comparison of 18F-FDG and 68Ga-DOTATATE PET/CT in surgically treated lung carcinoid tumors

Aims: This study aims to compare the efficacy of FDG-18 PET/CT and 68Ga-DOTATATE PET/CT imaging techniques in patients with lung carcinoid tumors, identifying the most appropriate preoperative nuclear medicine technique for diagnosis and staging. Methods: We retrospectively analyzed data from 123 patients who underwent surgery for lung carcinoid tumors at our center between 2009 and 2021. All of the patients were scanned with FDG-18 PET/CT before surgery. In addition to FDG-18 PET/CT, 68Ga-DOTATATE PET/CT scanning was performed in 28 patients: 17 in the preoperative and 11 in the postoperative period. Demographic data, mean higher maximal standard uptake (SUVmax) values of primary mass, lymph nodes and extrathoracic foci, pathologic subtype, and type of surgery were recorded. Compliance with normal distribution for numerical data was assessed using the Shapiro-Wilk test. The Wilcoxon signed-rank test was employed for groups meeting normal distribution to compare continuous numerical variables. The Mann-Whitney U and Kruskal-Wallis tests were used when normal distribution assumptions were unsatisfied. Results: The mean SUVmax value in 68Ga-DOTATATE PET/CT was significantly higher than FDG-18 PET/CT in patients with a lung carcinoid tumor (20 vs 4.4). For 68Ga-DOTATATE PET/CT scan, typical carcinoids had higher mean SUVmax value than atypical carcinoids (26 and 5.6 respectively), and the difference was statistically significant (p=0.002). For that FDG18 PET/CT, on the contrary, the mean SUVmax value was higher in atypical carcinoids than typical carcinoids (5.4 and 3.8, respectively), and the difference was not significant (p=0.126) Conclusion: The SUVmax values from 68Ga-DOTATATE PET/CT and FDG-18 PET/CT in lung carcinoid tumors vary by tumor subtype. 68Ga-DOTATATE PET/CT demonstrates higher SUVmax values in typical carcinoid tumors, indicating its superiority over FDG-18 PET/CT for this subtype. Although 68Ga-DOTATATE PET/CT also shows elevated SUVmax in atypical carcinoid tumors, the difference compared to FDG-18 PET/CT does not reach statistical significance.

Head-to-Head Comparison of 68Ga-FAPI-04 and 68Ga-DOTA-TATE PET/CT in Recurrent Medullary Thyroid Cancer.

We aimed to compare the diagnostic performance of 68Ga-FAPI-04 (FAPI) in comparison to 68Ga-DOTATATE (SSTR) PET/CT for patients presenting with recurrent medullary thyroid carcinoma (MTC). Sixteen MTC patients with elevated calcitonin levels (>150 pg/mL) underwent FAPI and SSTR PET/CT. Two nuclear medicine physicians evaluated all images, categorizing lesions into locoregional metastases, mediastinal lymph nodes (LNs), liver, and bone metastases. SUVmax and tumor-to-background ratio were recorded. PET modalities were compared using the McNemar test. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FAPI and SSTR PET were calculated. The cohort comprised 16 patients (50% female; mean age 50 ± 17 years). Median calcitonin and CEA levels were 6234 pg/mL and 17.3 ng/mL, respectively. In patient-based analysis, SSTR exhibited higher diagnostic sensitivity compared with FAPI (88% vs 81%), resulting a statistically significant difference (P = 0.004). Mean SUVmax and tumor-to-background ratio values were 10.3 and 5.35 for FAPI, and 9.7 and 11.9 for SSTR PET, respectively. In lesion-based analyses, FAPI demonstrated higher accuracy than SSTR for cervical LNs (91.9% vs 50%), mediastinal LNs (94.9% vs 54.4%), and liver metastases (57.4% vs 7.3%), respectively. Notably, 31% of patients (n = 5) with FAP-expressing liver lesions showed no uptake on SSTR imaging. MRI confirmed liver metastases in 3 of these patients; however, 2 FAP-expressing lesions were confirmed as hemangiomas. False-positive findings of DOTA primarily included reactive LNs and bone hemangiomas. FAPI PET presents promising outcomes in detecting metastases in recurrent MTC patients. Although its diagnostic performance matches SSTR on a per-patient basis, FAPI PET exhibits superior sensitivity and accuracy in lesion-based analyses, notably for liver and bone metastases.

Correlation between glucose metabolism and body mass index in tumor lesions of patients with lung cancer

ObjectiveLung cancer, along with various other cancers, is characterized by increased glucose metabolism. The maximum standardized uptake value (SUVmax), derived from positron emission tomography-computed tomography (PET-CT), serves as an indicator of glucose metabolic activity in tumor lesions. This study aimed to evaluate the correlation between body mass index (BMI) and SUVmax in individuals with lung cancer.MethodsThis study included 41 patients with lung cancer, who were divided into two groups: Group 1 (n = 21), with a BMI greater than 22.4, and Group 2 (n = 20), with a BMI less than 22.4. All participants underwent 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging. The SUVmax was calculated by manually delineating the regions of interest. A t-test was performed to assess whether the differences in SUVmax between the two groups were statistically significant.ResultsThe mean SUVmax for Group 1 was 11.20 ± 5.45, while for Group 2 it was 10.65 ± 5.96. Although the mean SUVmax was higher in Group 1 compared to Group 2, the difference between the groups was not statistically significant (P = 0.757).ConclusionThe findings indicate a non-significant difference in glucose metabolism in lung cancer lesions between patients with different BMI levels. These results offer valuable insights into the metabolic characteristics of lung cancer and contribute to a deeper understanding of its pathophysiology.

Non-invasive assessment of IgA nephropathy severity with [18F]AlF-NOTA-FAPI-04 PET/CT imaging.

Renal biopsy plays a crucial role in diagnosing and assessing the severity of immunoglobulin A nephropathy (IgAN), despite being an invasive procedure with potential risk of failure. Our study focused on evaluating the capability of [18F]AlF-NOTA-FAPI-04 PET/CT in identifying the extent of pathological alterations in IgAN. Twenty patients (13 males and 7 females; mean age, 44±16 years) with newly diagnosed primary IgAN and 10 patients (7 males and 3 females; mean age, 51±4 years) without known renal disease underwent [18F]AlF-NOTA-FAPI-04 PET/CT imaging. Kidney tissues from biopsies were stained with various techniques and examined using immunofluorescence. The Oxford classification was used to evaluate pathological indicators. Immunohistochemical staining was conducted to assess α-smooth muscle actin (αSMA) and fibroblast activation protein (FAP) expression. Renal FAPI uptake measured by positron emission tomography/computed tomography (PET/CT) (maximum and mean standardized uptake value, SUVmax and SUVmean) was correlated with histological findings. The renal parenchymal FAPI uptake was significantly higher in IgAN patients compared with control patients (SUVmax=3.9±1.3 vs 1.9±0.4, SUVmean=3.6±1.2 vs 1.5±0.4; all P<.001). We identified a significant difference in renal parenchymal FAPI uptake among the various categories of the Oxford classification. Correlation analysis revealed a positive association between SUVmax and interstitial fibrosis and tubular atrophy, as well as tubulointerstitial inflammation scores in scarred cortex and non-scarred cortex (r=0.637, 0.593 and 0.491, all P<.05), Similar associations were observed between SUVmean and these scores (r=0.641, 0.592 and 0.479, all P<.05). Furthermore, significant positive correlations were observed between SUVmax or SUVmean and the staining scores for glomerular αSMA and FAP, as well as for tubulointerstitial αSMA and FAP (all P<.01). [18F]AlF-NOTA-FAPI-04 PET/CT imaging offers IgAN patients a non-invasive and reproducible auxiliary modality to monitor disease progression.

Qualitative and quantitative analysis of 18F-GP1 positron emission tomography in thrombotic cardiovascular disease.

18F-GP1 is a novel highly specific radiotracer that binds to activated platelets and thrombus. We aimed to establish the observer repeatability of coronary, carotid and cerebral 18F-GP1 uptake in patients presenting with acute myocardial infarction or ischaemic stroke. Forty-three patients presenting with acute myocardial infarction or ischaemic stroke underwent hybrid positron emission tomography (PET) and computed tomography (CT) angiography. Qualitative and quantitative assessment of 18F-GP1 uptake was performed on coronary arteries, carotid arteries and brain parenchyma. Qualitative uptake of 18F-GP1 had excellent intraobserver and interobserver agreement, with complete agreement for the presence or absence of visual 18F-GP1 uptake. For quantitative analysis, there were excellent intraclass correlation coefficients for intraobserver repeatability for coronary artery, carotid artery and brain parenchymal SUVmax and TBRmax measurements (all ≥ 0.92). Coronary artery and brain parenchymal analyses showed the strongest agreement in SUVmax values with mean biases of - 0.04 (limits of agreement - 0.21 to 0.20) and 0.02 (limits of agreement - 0.29 to 0.32) respectively. There was good interclass correlation coefficients for interobserver repeatability for coronary artery, carotid artery and brain parenchymal SUVmax and TBRmax measurements (all ≥ 0.89). The strongest interobserver agreement was seen with brain parenchymal SUVmax (mean SUVmax 1.95 ± 0.94) and TBRmax (mean TBRmax 9.55 ± 6.56) with mean biases of - 0.05 (limits of agreement - 0.37 to 0.27) and 0.04 (limits of agreement - 0.59 to 0.52) respectively. Visual qualitative and quantitative 18F-GP1 PET-CT image analyses provide robust and repeatable measurements of activated platelets and thrombi within the coronary arteries, carotid arteries and brain parenchyma.

Head-to-Head Comparison of [68Ga]Ga-NOTA-RM26 and [18F]FDG PET/CT in Patients with Gastrointestinal Stromal Tumors: A Prospective Study.

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.

PET/CT imaging of differentiated and medullary thyroid carcinoma using the novel SSTR-targeting peptide [18F]SiTATE – first clinical experiences

PurposeThe novel 18F-labeled somatostatin receptor (SSTR)-directed radiotracer [18F]SiTATE demonstrated promising results for the imaging of various SSTR-expressing tumor types. Although thyroid carcinomas (TC) express SSTR, data on [18F]SiTATE PET/CT imaging in TC are lacking. This study explores the use of [18F]SiTATE PET/CT in a patient cohort with histologically proven TC.MethodsAs part of a prospective observational study at a single tertiary cancer center, 21 patients with TC (10 medullary (MTC) and 11 differentiated (DTC)) who underwent at least one [18F]SiTATE PET/CT were included (37 scans in total). Mean SUVmax and SUVmean of tumoral lesions, mean total-tumor-volume (TTV), and whole-body (WB)-SUVmax and WB-SUVmean on PET with their standard deviations (SDs) were determined. PET parameters were correlated to clinical parameters including tumor marker levels (thyroglobulin for DTC, calcitonin for MTC).Results89 lesions were included in the analysis. Metastases were localized in the bone, lymph nodes, lung, soft tissue, and thyroid bed. Osseous (31 lesions; SUVmax 8.6 ± 8.0; SUVmean 5.8 ± 5.4) and nodal (37 lesions; SUVmax 8.7 ± 7.8; SUVmean 5.7 ± 5.4) metastases showed the highest uptake. The MTC disease burden on PET significantly correlated with the calcitonin tumor marker level (e.g., TTV: r = 0.771, r2 = 0.594, p = 0.002). For DTC, no such correlation was present.ConclusionOur data demonstrate high feasibility of [18F]SiTATE PET/CT in a small cohort of patients with MTC and DTC. The use of [18F]SiTATE may overcome logistical disadvantages of 68Ga-based tracers and facilitate SSTR-targeted PET/CT imaging of thyroid carcinoma.

Assessment of pulmonary nodules using [18F]-FDG PET/CT in deep inspiration breath-hold

The characterization of pulmonary nodules (PN) is a primary indication for [18F]-FDG PET/CT. However, respiratory movements hinder this characterization, especially for PN located in the lower lobes. Various methods have been developed to improve image resolution. ObjectiveOur objective was to compare the diagnostic efficacy of [18F]-FDG PET/CT in deep inspiration breath-hold (DIBH) versus free-breathing corrected by software, in the evaluation of PN. MethodsWe prospectively analyzed 51 patients to assess PN using [18F]-FDG PET/CT in DIBH and free-breathing corrected by software. A total of 84 nodules with an average size of 10 mm were analyzed, with pathological anatomy or medical treatment decide by a multidisciplinary tumor board used as reference. ResultsA total of 84 PN were evaluated, comparing those in DIBH versus free-breathing, finding statistically significant differences in SUVmax values P(< 0.05) (mean SUVmax 3.7 in free-breathing vs. 5.33 in DIBH). When analyzed by location in lobes, we did not find statistically significant differences, though there was a trend towards higher SUVmax values in the lower lobes. [18F]-FDG PET/CT in DIBH showed high sensitivity (95%) and negative predictive value (NPV) (92%), indicating it may be a promising tool for PN characterization. ConclusionsThe acquisition of [18F]-FDG PET/CT in DIBH significantly improves the sensitivity and diagnostic efficacy in the assessment of PN. Although no statistically significant differences were found based on location, there is a potential benefit for the lower lobes. These findings could support its use in clinical practice.

18F-FDG PET/CT biomarkers as predictors of long term outcomes and survival rates in patients with high risk malignant pulmonary masses/nodules treated with stereotactic ablative radiotherapy.

Stereotactic ablative body radiotherapy (SABR) is a standard treatment option for patients with malignant pulmonary masses (including primary and metastatic lesions) who are unfit for surgery or who are medically operable but refuse surgery. Flourine-18 flurodeoxyglucose positron emission tomography (18F-FDG PET) volumetric metabolic parameters, i.e., metabolic tumour volume (MTV) and total lesion glycolysis (TLG) play an important role in assessing the biological characteristics of some tumours and its role as potential prognostic factors has also been introduced. The aim of this retrospective study is to assess the value of baseline metabolic volumetric parameters as prognostic imaging biomarkers in patients with pulmonary masses/nodules treated with SABR. 70 patients were included in this retrospective study (39 male and 31 female, age range 47-91years, mean 76years). Standardized uptake value (SUVmax), SUVmean, MTV and TLG for all the patients were calculated on baseline 18F-FDG PET/CT. Patient outcome was divided into 3 categories free of disease, stable disease and disease progression. There was no significant statistical difference in the SUVmax and SUVmean in all the three categories. Mean SUVmax ranges from 7.13 to 8.08 with its highest value in the stable disease and lowest value in the progressive disease categories. Similarly, the average SUVmean was 4.9 in the free of disease category and 4.68 in the progressive disease category. MTV and TLG were low in the free of disease and the highest in progressive disease. MTV increased from 2.25 cm3 in free of disease category to 3.23 cm3 and 7.29 cm3 in stable disease and progressive disease, respectively. TLG has increased from 11.7 in the disease-free survival category to 18.77 and 40.39 in the stable and progressive disease, respectively. Patients with low MTV had longer overall survival (OS) than patients with high MTV (37months versus 27months, p value = 0. 0018). In addition, OS was longer in patients with low TLG (36months versus 24months, p value = 0.016). TLG and MTV are more useful than SUVmax and SUVmean for predicting outcome, OS and progression-free survival (PFS) in patients receiving SABR. The TLG and MTV measurement on 18F-FDG PET imaging may be routinely recommended in baseline 18F-FDG PET/CT prior to SABR.

68Ga]Ga-RAYZ-8009: A Glypican-3-Targeted Diagnostic Radiopharmaceutical for Hepatocellular Carcinoma Molecular Imaging-A First-in-Human Case Series.

To date, the imaging and diagnosis of hepatocellular carcinoma (HCC) rely on CT/MRI, which have well-known limitations. Glypican-3 (GPC3) is a cell surface receptor highly expressed by HCC but not by normal or cirrhotic liver tissue. Here we report initial clinical results of GPC3-targeted PET imaging with [68Ga]Ga-DOTA-RYZ-GPC3 (RAYZ-8009), a peptide-based GPC3 ligand in patients with known or suspected HCC. Methods: [68Ga]Ga-RAYZ-8009 was obtained after labeling the peptide precursor with 68Ga from a 68Ge/68Ga generator and heating at 90°C for 10 min followed by sterile filtration. After administration of [68Ga]Ga-RAYZ-8009, a dynamic or static PET/CT scan was acquired between 45 min and 4 h after administration. Radiotracer uptake was measured by SUVs for the following tissues: suspected or actual HCC or hepatoblastoma lesions, non-tumor-bearing liver, renal cortex, blood pool in the left ventricle, and gastric fundus. Additionally, tumor-to-healthy-liver ratios (TLRs) were calculated. Results: Twenty-four patients (5 patients in the dynamic protocol; 19 patients in the static protocol) were scanned. No adverse events occurred. Two patients had no lesion detected and did not have HCC during follow-up. In total, 50 lesions were detected and analyzed. The mean SUVmax of these lesions was 19.6 (range, 2.7-95.3), and the mean SUVmean was 10.1 (range, 1.0-49.2) at approximately 60 min after administration. Uptake in non-tumor-bearing liver and blood pool rapidly decreased over time and became negligible 45 min after administration (mean SUVmean, <1.6), with a continuous decline to 4 h after administration (mean SUVmean, 1.0). The opposite was observed for HCC lesions, for which SUVs and TLRs continuously increased for up to 4 h after administration. In individual lesion analysis, TLR was the highest between 60 and 120 min after administration. Uptake in the gastric fundus gradually increased for up to 45 min (to an SUVmax of 31.3) and decreased gradually afterward. Conclusion: [68Ga]Ga-RAYZ-8009 is safe and allows for high-contrast imaging of GPC3-positive HCC, with rapid clearance from most normal organs. Thereby, [68Ga]Ga-RAYZ-8009 is promising for HCC diagnosis and staging. Further research is warranted.

Detection of tumour heterogeneity in patients with advanced, metastatic castration-resistant prostate cancer on [68Ga]Ga-/[18F]F-PSMA-11/-1007, [68Ga]Ga-FAPI-46 and 2-[18F]FDG PET/CT: a pilot study

PurposeIn metastatic castration-resistant prostate cancer (mCRPC), some patients show low/absent PSMA expression in tumour lesions on positron emission tomography (PET) scans, indicating heterogeneity and heightened risk of non-response to PSMA-RLT (radioligand therapy). Imaging cancer-associated fibroblasts and glucose uptake may further characterise tumour heterogeneity in mCRPC patients. Here, we aimed to evaluate tumour heterogeneity and its potential implications for management in mCRPC patients assessed for PSMA-RLT using [68Ga]Ga-FAPI-46, 2-[18F]FDG and [68Ga]Ga-/[18F]F-PSMA-11/-1007 PET.Material and MethodsPatients with advanced, progressive mCRPC underwent clinical [68Ga]Ga-/[18F]F-PSMA-11/-1007, 2-[18F]FDG and [68Ga]Ga-FAPI-46 PET/CT to evaluate treatment with PSMA-directed RLT. Tumour detection/semiquantitative parameters were compared on a per-lesion/-region basis. Two phenotypes were defined: Criteria for the mixed phenotype were: (a) PSMA-negative findings for lymph node metastases ≥ 2.5 cm, any solid organ metastases ≥ 1.0 cm, or bone metastases with soft tissue component ≥ 1.0 cm, (b) low [68Ga]Ga-/[18F]F-PSMA-11/-1007 uptake and/or (c) balanced tumour uptake of all radioligands. The PSMA-dominant phenotype was assigned if the criteria were not met.ResultsIn ten patients, 472 lesions were detected on all imaging modalities (miTNM regions: M1b: 327 (69.3%), M1a: 95 (20.1%), N1: 26 (5.5%), M1c: 18 (3.8%), T: 5 (1.1%) and Tr: 1 (0.2%). [68Ga]Ga-/[18F]F-PSMA-11/-1007 (n = 453 (96.0%)) demonstrates the highest detection rate, followed by [68Ga]Ga-FAPI-46 (n = 268 (56.8%))/2-[18F]FDG (n = 241 (51.1%)). Semiquantitative uptake was highest for [68Ga]Ga-/[18F]F-PSMA-11/-1007 (mean SUVmax (interquartile range): 22.7 (22.5), vs. [68Ga]Ga-FAPI-46 (7.7 (3.7)) and 2-[18F]FDG (6.8 (4.7)). Seven/three patients were retrospectively assigned to the PSMA-dominant/mixed phenotype. Median overall survival was significantly longer for patients who underwent [177Lu]Lu-PSMA-617 RLT and were retrospectively assigned to the PSMA-dominant phenotype (19.7 vs. 9.3 months).ConclusionThrough whole-body imaging, we identify considerable inter- and intra-patient heterogeneity of mCRPC and potential imaging phenotypes. Regarding uptake and tumour detection, [68Ga]Ga-/[18F]F-PSMA-11/-1007 was superior to [68Ga]Ga-FAPI-46 and 2-[18F]FDG, while the latter two were comparable. Patients who underwent [177Lu]Lu-PSMA-617 RLT based on clinical-decision making had a longer overall survival and could be assigned to the PSMA-dominant phenotype.Graphical

Evaluation of 68Ga-FAPI PET/CT and 18F-FDG PET/CT for the diagnosis of recurrent colorectal cancers

ObjectiveThe present study aimed to compare the diagnostic value of gallium-68-labeled fibroblast activation protein inhibitor positron emission tomography/computed tomography (68Ga-FAPI PET/CT) and fluorine-18-labeled fluorodeoxyglucose PET/CT (18F-FDG PET/CT) for detecting recurrent colorectal cancers (CRCs). Materials and MethodsFifty-six patients (age: 18–80 years, 31 men and 25 women) with suspected recurrent CRC were enrolled and underwent 18F-FDG PET/CT and 68Ga-FAPI PET/CT sequentially within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were estimated and compared between the two modalities by using Student’s t-test. The Wilcoxon signed-rank test was used to compare peritoneal carcinoma index (PCI) scores between the two imaging modalities. Results68Ga-FAPI PET/CT showed higher sensitivity for detecting recurrence (93 % vs. 79 %); lymph node metastasis (89 % vs. 78 %), particularly peritoneal lymph node metastasis (92 % vs. 63 %); and metastatic implantation on the intestinal wall (100 % vs. 25 %) compared to 18F-FDG PET/CT. However, 68Ga-FAPI PET/CT showed lower sensitivity for detecting bone metastasis (67 % vs. 100 %). The mean SUVmax values of peritoneal metastases and metastatic implantation on the intestinal wall were 4.28 ± 2.70 and 7.58 ± 1.66 for 18F-FDG PET/CT and 5.66 ± 1.97 and 6.70 ± 0.25 for 68Ga-FAPI PET/CT, respectively. Furthermore, 68Ga-FAPI PET/CT showed significantly higher TBR for peritoneal metastatic lesions (4.22 ± 1.47 vs. 1.41 ± 0.89, p < 0.0001) and metastatic implantation on the intestinal wall (5.63 ± 1.24 vs. 2.20 ± 0.5, p = 0.02) compared to 18F-FDG PET/CT. For the same patient, 68Ga-FAPI PET/CT yielded a more accurate PCI score and a greater area under the curve value for the receiver operating characteristic curve (p < 0.01) than 18F-FDG PET/CT. Conclusion68Ga-FAPI PET/CT was superior to 18F-FDG PET/CT for detecting recurrence and peritoneal metastases. Hence, we propose the combination of these two modalities for better clinical diagnosis and management of patients with CRC.

[68 Ga]Ga-CXCR4 PET/CT imaging in high-grade glioma for assessment of CXCR4 receptor expression

PurposeGliomas account for 75 % of primary malignant CNS tumors. High-grade glioma (CNS WHO grades 3 and 4) have an unfavorable treatment response and poor outcome. CXCR4 is a G protein-coupled receptor that plays an important part in the signaling pathway between cancer cells and tumor microenvironment. CXCR4 overexpression has been shown in a variety of cancers. In this study, we evaluate the potential value of [68Ga]Ga-Pentixafor as a PET/CT CXCR4-probe for in vivo assessment of CXCR4 expression in patients with high-grade glioma and its correlation with tumor grade. Materials and Methods[68Ga]Ga-CXCR4 PET/CT was performed in the prospective single-center study in treatment-naïve biopsy-proven patients with high-grade glioma. The acquired images were analyzed qualitatively and semi-quantitatively. ResultA total of 26 patients (mean age: 53.3±14.4 years, 11 women, 15 men) were enrolled. CNS WHO grade 3 pathology was seen in 19 % (5/26) of the sample. The patient-based sensitivity of 68Ga-CXCR4 was 96.2 %. Overall, 28 pathologic lesions were detected, leading to a lesion-based sensitivity of 96.4 %. The median (IQR) SUVmax of grade 4 lesions was substantially greater than the grade 3(3.03(2.5–3.7) vs. 1.51(1.2–1.8), p = 0.0145).). The highest tracer activity of organs −beside bladder as the main excretion reservoir-was in lymphoid tissue of Waldeyer’s ring (mean SUVmax: 7.41), and spleen (mean SUVmax: 6.62). ConclusionIn conclusion, this new application for [68Ga]Ga-Pentixafor PET tracer exhibits excellent visual and semi-quantitative diagnostic properties. Further studies are warranted.