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18F-Alfatide II PET/CT for Identification of Breast Cancer: A Preliminary Clinical Study.

ABSTRACT: 18F-alfatide II has been proven to have excellent clinical translational potential. In this study, we investigated 18F-alfatide II for identifying breast cancer and compared the performances between 18F-alfatide II and 18F-FDG. Methods: Forty-four female patients with suspected primary breast cancer were recruited. PET/CT images using 18F-alfatide II and 18F-FDG were acquired within 7 d. Tracer uptake in breast lesions was evaluated by visual analysis, and semiquantitative analysis with SUVmax and SUVmean Results: Forty-two breast cancer lesions and 11 benign breast lesions were confirmed by histopathology in 44 patients. Both 18F-alfatide II and 18F-FDG had higher uptake in breast cancer lesions than in benign breast lesions (P < 0.05 for 18F-alfatide II, P < 0.05 for 18F-FDG). The area under the curve of 18F-alfatide II was slightly less than that of 18F-FDG. Both 18F-alfatide II and 18F-FDG had high sensitivity (88.1% vs. 90.5%), high positive predictive value (88.1% vs. 88.4%), moderate specificity (54.5% vs. 54.5%), and moderate negative predictive value (54.5% vs. 60.0%) for differentiating breast cancer from benign breast lesions. By combining 18F-alfatide II and 18F-FDG, the sensitivity and negative predictive value significantly increased to 97.6% and 85.7%, respectively, with positive predictive value slightly increased to 89.1% and no change to the specificity (54.5%). The uptake of 18F-alfatide II (SUVmax: 3.77 ± 1.78) was significantly lower than that of 18F-FDG (SUVmax: 7.37 ± 4.48) in breast cancer lesions (P < 0.05). 18F-alfatide II uptake in triple-negative subtype was significantly lower than that in luminal A and luminal B subtypes. By contrast, human epidermal growth factor receptor-2 (HER-2)-overexpressing subtype had higher 18F-FDG uptake than the other 3 subtypes. There were 8 breast cancer lesions with higher 18F-alfatide II uptake than 18F-FDG uptake, which all had a common characteristic that HER-2 expression was negative and estrogen receptor expression was strongly positive. Conclusion: 18F-alfatide II is suitable for clinical use in breast cancer patients. 18F-alfatide II is of good performance, but not superior to 18F-FDG in identifying breast cancer. 18F-alfatide II may have superiority to 18F-FDG in detecting breast cancer with strongly positive estrogen receptor expression and negative HER-2 expression.

SUBMITTER: Wu J

PROVIDER: S-EPMC6910641 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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18F-Alfatide II PET/CT for Identification of Breast Cancer: A Preliminary Clinical Study.

Wu Jiang J Wang Shaohua S Zhang Xianzhong X Teng Zhaogang Z Wang Jingjie J Yung Bryant C BC Niu Gang G Zhu Hong H Lu Guangming G Chen Xiaoyuan X

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20180426 12

18F-alfatide II has been proven to have excellent clinical translational potential. In this study, we investigated 18F-alfatide II for identifying breast cancer and compared the performances between 18F-alfatide II and 18F-FDG. Methods: Forty-four female patients with suspected primary breast cancer were recruited. PET/CT images using 18F-alfatide II and 18F-FDG were acquired within 7 d. Tracer uptake in breast lesions was ...[more]

PMID: 29700127

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Project description:Backgroundsignificance of incidental thyroid 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake on positron emission tomography/computed tomography (PET/CT) scans remains controversial. We aimed to evaluate the ability of [18F]FDG-PET/CT texture analysis to predict final diagnosis in thyroid incidentaloma.MethodsWe retrospectively evaluated medical records of all patients who performed a [18F]FDG-PET/CT from January 2012 to October 2016. Those patients who presented a thyroid incidentaloma described in the medical records and performed a fine needle aspiration in our institution were considered for the analysis. Cytological and/or histological results were used as reference standard to define the final diagnosis. In case of negative cytology, the nodule was considered benign. In case of non-diagnostic or inconclusive results ultrasound, follow-up and further cytology/histology were used as final diagnosis. For suspected or positive cytological result, histology was used as reference standard. PET images were segmented using a General Electric AW workstation running PET VCAR software (GE Healthcare, Waukesha, WI, USA) settled with a threshold of 40% SUVmax. LifeX software (http://www.lifexsoft.org) was used to perform texture analysis. Statistical analysis was performed with R package (https://www.r-project.org).ResultsWe identified 55 patients with incidental thyroid [18F]FDG uptake. Five patients were excluded from the analysis because a final diagnosis was not available. Thirty-two out of 50 patients had benign nodules while in 18/50 cases a malignancy (primary thyroid cancer = 15, metastases = 3) was diagnosed. Conventional PET parameters and histogram-based features were calculated for all 50 patients, while other matrices-based features were available for 28/50 patients. SUVmax and skewness resulted significantly different in benign and malignant nodules (p = 0.01 and = 0.02, respectively). Using ROC analysis, seven features were identified as potential predictors. Among all the textural features tested, skewness showed the best area under the curve (=?0.66). SUV-based parameters resulted in the highest specificity while MTV, TLG, skewness and kurtosis, as well as correlationGLCM resulted better in sensitivity.Conclusions[18F]FDG-PET/CT texture analysis seems to be a promising approach to stratify the patients with thyroid incidentaloma identified on PET scans, with respect to the risk of the diagnosis of a malignant thyroid nodule and thus, could refine the selection of the patients to be referred for cytology.

Project description:Background & aimsThe vitronectin receptor integrin αvβ3 drives fibrogenic activation of hepatic stellate cells (HSCs). Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on activated HSCs (aHSCs) in the injured liver. In this study, we sought to compare differences in the uptake of [18F]-Alfatide between normal and injured liver to evaluate its utility for assessment of hepatic fibrogenesis.MethodsPET with [18F]-Alfatide, non-enhanced CT, histopathology, immunofluorescence staining, immunoblotting and gene analysis were performed to evaluate and quantify hepatic integrin αvβ3 levels and liver fibrosis progression in mouse models of fibrosis (carbon tetrachloride [CCl4] and bile duct ligation [BDL]). The liver AUC divided by the blood AUC over 30 min was used as an integrin αvβ3-PET index to quantify fibrosis progression. Ex vivo analysis of frozen liver tissue from patients with fibrosis and cirrhosis verified the animal findings.ResultsFibrotic mouse livers showed enhanced [18F]-Alfatide uptake and retention compared to control livers. The radiotracer was demonstrated to bind specifically with integrin αvβ3, which is mainly expressed on aHSCs. Autoradiography and histopathology confirmed the PET imaging results. Further, the mRNA and protein level of integrin αvβ3 and its signaling complex were higher in CCl4 and BDL models than controls. The results obtained from analyses on human fibrotic liver sections supported the animal findings.ConclusionsImaging hepatic integrin αvβ3 with PET and [18F]-Alfatide offers a potential non-invasive method for monitoring the progression of liver fibrosis.Lay summaryIntegrin αvβ3 expression on activated hepatic stellate cells (aHSCs) is associated with HSC proliferation during hepatic fibrogenesis. Herein, we show that a radioactive tracer, [18F]-Alfatide, binds to integrin αvβ3 with high affinity and specificity. [18F]-Alfatide could thus be used as a non-invasive imaging biomarker to track hepatic fibrosis progression.

Project description:Background[18F]-fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) has been implemented sporadically in hospital settings as the standard of care examination for recurrent breast cancer. We aimed to explore the clinical impact of implementing [18F]FDG-PET/CT for patients with clinically suspected recurrent breast cancer and validate the diagnostic accuracy.MethodsWomen with suspected distant recurrent breast cancer were prospectively enrolled in the study between September 2017 and August 2019. [18F]FDG-PET/CT was performed, and the appearance of incidental benign and malignant findings was registered. Additional examinations, complications, and the final diagnosis were registered to reflect the clinical consequence of such findings. The diagnostic accuracy of [18F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard.Results[18F]FDG-PET/CT reported breast cancer metastases in 72 of 225 women (32.0%), and metastases were verified by biopsy in 52 (52/225, 23.1%). Prior probability and posterior probability of a positive test for suspected metastatic cancer and incidental malignancies were 27%/85% and 4%/20%, respectively. Suspected malignant incidental findings were reported in 46 patients (46/225, 20.4%), leading to further examinations and final detection of nine synchronous cancers (9/225, 4.0%). These cancers originated from the lung, thyroid, skin, pancreas, peritoneum, breast, kidney, one was malignant melanoma, and one was hematological cancer. False-positive incidental malignant findings were examined in 37/225 patients (16.4%), mainly in the colon (n = 12) and thyroid gland (n = 12). Ten incidental findings suspicious for benign disease were suggested by [18F]FDG-PET/CT, and further examinations resulted in the detection of three benign conditions requiring treatment. Sensitivity, specificity, and AUC-ROC for diagnosing distant metastases were 1.00 (0.93-1.0), 0.88 (0.82-0.92), and 0.98 (95% CI 0.97-0.99), respectively.Conclusion[18F]FDG-PET/CT provided a high posterior probability of positive test, and a negative test was able to rule out distant metastases in women with clinically suspected recurrent breast cancer. One-fifth of patients examined for incidental findings detected on [18F]FDG-PET/CT were diagnosed with clinically relevant conditions. Further examinations of false-positive incidental findings in one of six women should be weighed against the high accuracy for diagnosing metastatic breast cancer. Trial registration Clinical.Trials.gov. NCT03358589. Registered 30 November 2017-Retrospectively registered, http://www.ClinicalTrials.gov.

Project description:This study aimed to compare contrast-enhanced CT (CE-CT) and 18F-FDG PET/CT for response monitoring in metastatic breast cancer using the standardized response evaluation criteria RECIST 1.1 and PERCIST. The objective was to examine whether progressive disease was detected systematically earlier by one of the modalities. Methods: Women with biopsy-verified metastatic breast cancer were enrolled prospectively and monitored using combined CE-CT and 18F-FDG PET/CT every 9-12 wk to evaluate response to first-line treatment. CE-CT scans and RECIST 1.1 were used for clinical decision-making without accessing the 18F-FDG PET/CT scans. At study completion, 18F-FDG PET/CT scans were unmasked and assessed according to PERCIST. Visual assessment was used if response criteria could not be applied. The modality-specific time to progression was defined as the time from the baseline scan until the first scan demonstrating progression. Paired comparative analyses for CE-CT versus 18F-FDG PET/CT were applied, and the primary endpoint was earlier detection of progression by one modality. Secondary endpoints were time to detection of progression, response categorization, visualization of changes in response over time, and measurable disease according to RECIST and PERCIST. Results: In total, 87 women were evaluable, with a median of 6 (1-11) follow-up scans. Progression was detected first by 18F-FDG PET/CT in 43 (49.4%) of 87 patients and first by CE-CT in 1 (1.15%) of 87 patients (P < 0.0001). Excluding patients without progression (n = 32), progression was seen first on 18F-FDG PET/CT in 78.2% (43/55) of patients. The median time from detection of progression by 18F-FDG PET/CT to that of CE-CT was 6 mo (95% CI, 4.3-6.4 mo). At baseline, 76 (87.4%) of 87 patients had measurable disease according to PERCIST and 51 (58.6%) of 87 patients had measurable disease according to RECIST 1.1. Moreover, 18F-FDG PET/CT provided improved visualization of changes in response over time, as seen in the graphical abstract. Conclusion: Disease progression was detected earlier by 18F-FDG PET/CT than by CE-CT in most patients, with a potentially clinically relevant median 6-mo delay for CE-CT. More patients had measurable disease according to PERCIST than according to RECIST 1.1. The magnitude of the final benefit for patients is a perspective for future research.

Project description:Invasive lobular carcinoma (ILC) demonstrates lower conspicuity on 18F-FDG PET than the more common invasive ductal carcinoma. Other molecular imaging methods may be needed for evaluation of this malignancy. As ILC is nearly always (95%) estrogen receptor (ER)-positive, ER-targeting PET tracers such as 16α-18F-fluoroestradiol (18F-FES) may have value. We reviewed prospective trials at Memorial Sloan Kettering Cancer Center using 18F-FES PET/CT to evaluate metastatic ILC patients with synchronous 18F-FDG and 18F-FES PET/CT imaging, which allowed a head-to-head comparison of these 2 PET tracers. Methods: Six prospective clinical trials using 18F-FES PET/CT in patients with metastatic breast cancer were performed at Memorial Sloan Kettering Cancer Center from 2008 to 2019. These trials included 92 patients, of whom 14 (15%) were of ILC histology. Seven of 14 patients with ILC had 18F-FDG PET/CT performed within 5 wk of the research 18F-FES PET/CT and no intervening change in management. For these 7 patients, the 18F-FES and 18F-FDG PET/CT studies were analyzed to determine the total number of tracer-avid lesions, organ systems of involvement, and SUVmax of each organ system for both tracers. Results: In the 7 comparable pairs of scans, there were a total of 254 18F-FES-avid lesions (SUVmax, 2.6-17.9) and 111 18F-FDG-avid lesions (SUVmax, 3.3-9.9) suggestive of malignancy. For 5 of 7 (71%) ILC patients, 18F-FES PET/CT detected more metastatic lesions than 18F-FDG PET/CT. In the same 5 of 7 patients, the SUVmax of 18F-FES-avid lesions was greater than the SUVmax of 18F-FDG-avid lesions. One patient had 18F-FES-avid metastases with no corresponding 18F-FDG-avid metastases. There were no patients with 18F-FDG-avid distant metastases without 18F-FES-avid distant metastases, although in one patient liver metastases were evident on 18F-FDG but not on 18F-FES PET. Conclusion: 18F-FES PET/CT compared favorably with 18F-FDG PET/CT for detection of metastases in patients with metastatic ILC. Larger prospective trials of 18F-FES PET/CT in ILC should be considered to evaluate ER-targeted imaging for clinical value in patients with this histology of breast cancer.

Project description:PurposeThis study aimed to assess the diagnostic performance of [18F]FAPI-42 PET/CT and compare it with that of 2-[18F]FDG PET/CT in patients with differentiated thyroid cancer (DTC) with biochemical elevations in Tg or anti-Tg antibodies.MethodsA total of 42 patients with DTC with biochemical elevations in Tg or anti-Tg antibodies underwent [18F]FAPI-42 PET/CT as part of this study; of which, 11 additionally underwent 2-[18F]FDG PET/CT within 7 days. Images were semi-quantitatively and visually interpreted, and the quantity, location, and uptake values of lesions were noted. The diagnostic capacity of [18F]FAPI-42 PET/CT and biomarkers affecting the uptake of [18F]FAPI-42 were evaluated. In addition, the diagnostic performance and uptake of [18F]FAPI-42 and 2-[18F]FDG were compared, and the correlation between lesion diameter and quantitative parameters was investigated.ResultsA total of 161 lesions were detected in 27 (64%) patients on [18F]FAPI-42 PET/CT. FAPI-positive local recurrence showed the highest uptake intensity, followed by lymphatic, other site-associated (bone and pleura), and pulmonary lesions (mean SUVmax, 4.7 versus 3.7 versus 3.0 versus 2.2, respectively; P < 0.0001). The levels of TSH, Tg, and Tg-Ab did not affect the uptake value of lesions (median SUVmax: 2.4 versus 3.2, P = 0.56; 2.9 versus 2.4, P = 0.0935; 2.8 versus 2.6, P = 0.0525, respectively). A total of 90 positive lesions were detected in 7 patients using both modalities. All positive lesions showed statistically higher uptake of 2-[18F]FDG than that of [18F]FAPI-42 (SUVmax, 2.6 versus 2.1; P = 0.026). However, the SUVmax of [18F]FAPI-42 was higher than that of 2-[18F]FDG in local recurrences and lymphatic lesions (SUVmax, 4.2 versus 2.9 and 3.9 versus 3.4, respectively; P > 0.05).Conclusion[18F]FAPI-42 can be used for detecting lesions and reflecting FAP expression during local recurrence and metastasis in patients with DTC with biochemical elevations in Tg or anti-Tg antibodies. The diagnostic performance of [18F]FAPI-42 PET/CT is comparable with that of 2-[18F]FDG PET/CT in such patients.

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18F-Alfatide II PET/CT for Identification of Breast Cancer: A Preliminary Clinical Study.

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<sup>18</sup>F-Alfatide II PET/CT for Identification of Breast Cancer: A Preliminary Clinical Study.

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