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Pilot Prospective Evaluation of (18)F-Alfatide II for Detection of Skeletal Metastases.

ABSTRACT: This pilot prospective evaluation study is to verify the efficiency of (18)F-Alfatide II, a specific PET imaging agent for integrin ?v?3, in detecting bone metastasis in human, with comparison to (18)F-FDG PET. Thirty recruited patients underwent (18)F-FDG and (18)F-alfatide II PET/CT successively within days. The final diagnosis of bone lesions was established based on the comprehensive assessment of all available data and clinical follow-up, which fall into four groups: osteolytic, osteoblastic, mixed and bone marrow. Visual analysis and quantification of SUVmax were performed to compare the detection sensitivity of (18)F-Alfatide II and (18)F-FDG PET. Eleven patients were found to have a total of 126 bone metastasis lesions. (18)F-Alfatide II PET can detect the bone metastatic lesions with good contrast and higher sensitivity (positive rate of 92%) than (18)F-FDG PET (77%). Especially, (18)F-Alfatide II PET showed superiority to (18)F-FDG PET in detecting osteoblastic (70% vs. 53%) and bone marrow metastatic lesions (98% vs. 77%). In conclusion, (18)F-Alfatide II PET/CT can be used to detect skeletal and bone marrow metastases, with nearly 100% sensitivity in osteolytic, mixed and bone marrow lesions. The sensitivity of (18)F-Alfatide II PET/CT in osteoblastic metastases is relatively low but still significantly higher than that of (18)F-FDG PET/CT. This pilot clinical study warrants the further application of (18)F-Alfatide II PET/CT in metastatic lesion detection, patient management and drug therapy response monitoring.

SUBMITTER: Mi B

PROVIDER: S-EPMC4508500 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Pilot Prospective Evaluation of (18)F-Alfatide II for Detection of Skeletal Metastases.

Mi Baoming B Yu Chunjing C Pan Donghui D Yang Min M Wan Weixing W Niu Gang G Chen Xiaoyuan X

Theranostics 20150712 10

This pilot prospective evaluation study is to verify the efficiency of (18)F-Alfatide II, a specific PET imaging agent for integrin αvβ3, in detecting bone metastasis in human, with comparison to (18)F-FDG PET. Thirty recruited patients underwent (18)F-FDG and (18)F-alfatide II PET/CT successively within days. The final diagnosis of bone lesions was established based on the comprehensive assessment of all available data and clinical follow-up, which fall into four groups: osteolytic, osteoblasti ...[more]

PMID: 26199649

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Project description:A single dynamic PET acquisition using multiple tracers administered closely in time could provide valuable complementary information about a tumor's status under quasiconstant conditions. This study aimed to investigate the utility of dual-tracer dynamic PET imaging with (18)F-alfatide II ((18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2) and (18)F-FDG for parametric monitoring of tumor responses to therapy.We administered doxorubicin to one group of athymic nude mice with U87MG tumors and paclitaxel protein-bound particles to another group of mice with MDA-MB-435 tumors. To monitor therapeutic responses, we performed dual-tracer dynamic imaging, in sessions that lasted 90 min, starting with injection via the tail vein catheters with (18)F-alfatide II, followed 40 min later by (18)F-FDG. To achieve signal separation of the 2 tracers, we fit a 3-compartment reversible model to the time-activity curve of (18)F-alfatide II for the 40 min before (18)F-FDG injection and then extrapolated to 90 min. The (18)F-FDG tumor time-activity curve was isolated from the 90-min dual-tracer tumor time-activity curve by subtracting the fitted (18)F-alfatide II tumor time-activity curve. With separated tumor time-activity curves, the (18)F-alfatide II binding potential (Bp = k3/k4) and volume of distribution (VD) and (18)F-FDG influx rate ((K1 × k3)/(k2 + k3)) based on the Patlak method were calculated to validate the signal recovery in a comparison with 60-min single-tracer imaging and to monitor therapeutic response.The transport and binding rate parameters K1-k3 of (18)F-alfatide II, calculated from the first 40 min of the dual-tracer dynamic scan, as well as Bp and VD correlated well with the parameters from the 60-min single-tracer scan (R(2) > 0.95). Compared with the results of single-tracer PET imaging, (18)F-FDG tumor uptake and influx were recovered well from dual-tracer imaging. On doxorubicin treatment, whereas no significant changes in static tracer uptake values of (18)F-alfatide II or (18)F-FDG were observed, both (18)F-alfatide II Bp and (18)F-FDG influx from kinetic analysis in tumors showed significant decreases. For therapy of MDA-MB-435 tumors with paclitaxel protein-bound particles, a significant decrease was observed only with (18)F-alfatide II Bp value from kinetic analysis but not (18)F-FDG influx.The parameters fitted with compartmental modeling from the dual-tracer dynamic imaging are consistent with those from single-tracer imaging, substantiating the feasibility of this methodology. Even though no significant differences in tumor size were found until 5 d after doxorubicin treatment started, at day 3 there were already substantial differences in (18)F-alfatide II Bp and (18)F-FDG influx rate. Dual-tracer imaging can measure (18)F-alfatide II Bp value and (18)F-FDG influx simultaneously to evaluate tumor angiogenesis and metabolism. Such changes are known to precede anatomic changes, and thus parametric imaging may offer the promise of early prediction of therapy response.

Project description: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.

Project description:PurposeMeta-[18F]fluorobenzylguanidine ([18F]mFBG) is a positron emission tomography (PET) radiotracer that allows for fast and high-resolution imaging of tumours expressing the norepinephrine transporter. This pilot study investigates the feasibility of [18F]mFBG PET-CT for imaging in neuroblastoma.MethodsIn a prospective, single-centre study, we recruited children with neuroblastoma, referred for meta-[123I]iodobenzylguanidine ([123I]mIBG) scanning, consisting of total body planar scintigraphy in combination with single-photon emission computed tomography-CT (SPECT-CT). Within two weeks of [123I]mIBG scanning, total body PET-CTs were performed at 1 h and 2 h after injection of [18F]mFBG (2 MBq/kg). Detected tumour localisations on scan pairs were compared. Soft tissue disease was quantified by number of lesions and skeletal disease by SIOPEN score.ResultsTwenty paired [123I]mIBG and [18F]mFBG scans were performed in 14 patients (median age 4.9 years, n = 13 stage 4 disease and n = 1 stage 4S). [18F]mFBG injection was well tolerated and no related adverse events occurred in any of the patients. Mean scan time for [18F]mFBG PET-CT (9.0 min, SD 1.9) was significantly shorter than for [123I]mIBG scanning (84.5 min, SD 10.5), p < 0.01. Most tumour localisations were detected on the 1 h versus 2 h post-injection [18F]mFBG PET-CT. Compared to [123I]mIBG scanning, [18F]mFBG PET-CT detected a higher, equal, and lower number of soft tissue lesions in 40%, 55%, and 5% of scan pairs, respectively, and a higher, equal, and lower SIOPEN score in 55%, 30%, and 15% of scan pairs, respectively. On average, two more soft tissue lesions and a 6-point higher SIOPEN score were detected per patient on [18F]mFBG PET-CT compared to [123I]mIBG scanning.ConclusionResults of this study demonstrate feasibility of [18F]mFBG PET-CT for neuroblastoma imaging. More neuroblastoma localisations were detected on [18F]mFBG PET-CT compared to [123I]mIBG scanning. [18F]mFBG PET-CT shows promise for future staging and response assessment in neuroblastoma.Trial registrationDutch Trial Register NL8152.

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:OBJECTIVE. The purpose of this study was to assess the utility of PET with (2S)-2-[[(1S)-1-carboxy-5-[(6-(18F)fluoranylpyridine-3-carbonyl)amino]pentyl]carbamoylamino]pentanedioic acid (18F-DCFPyL), a prostate-specific membrane antigen (PSMA)-targeted radiotracer, in the detection of high-risk localized prostate cancer as compared with multiparametric MRI (mpMRI). SUBJECTS AND METHODS. This HIPAA-compliant prospective study included 26 consecutive patients with localized high-risk prostate cancer (median age, 69.5 years [range, 53-81 years]; median prostate-specific antigen [PSA] level, 18.88 ng/mL [range, 1.03-20.00 ng/mL]) imaged with 18F-DCFPyL PET/CT and mpMRI. Images from PET/CT and mpMRI were evaluated separately, and suspicious areas underwent targeted biopsy. Lesion-based sensitivity and tumor detection rate were compared for PSMA PET and mpMRI. Standardized uptake value (SUV) and PSMA PET parameters were correlated with histopathology score, and uptake in tumor was compared with that in nonmalignant tissue. On a patient level, SUV and PSMA tumor volume were correlated with PSA density. RESULTS. Forty-four tumors (one in Gleason grade [GG] group 1, 12 in GG group 2, seven in GG group 3, nine in GG group 4, and 15 in GG group 5) were identified at histopathology. Sensitivity and tumor detection rate of 18F-DCFPyL PET/CT and mpMRI were similar (PET/CT, 90.9% and 80%; mpMRI, 86.4% and 88.4%; p = 0.58/0.17). Total lesion PSMA and PSMA tumor volume showed a relationship with GG (τ = 0.27 and p = 0.08, τ = 0.30 and p = 0.06, respectively). Maximum SUV in tumor was significantly higher than that in nonmalignant tissue (p < 0.05). Tumor burden density moderately correlated with PSA density (r = 0.47, p = 0.01). Five true-positive tumors identified on 18F-DCFPyL PET/CT were not identified on mpMRI. CONCLUSION. In patients with high-risk prostate cancer, 18F-DCFPyL PET/CT is highly sensitive in detecting intraprostatic tumors and can detect tumors missed on mpMRI. Measured uptake is significantly higher in tumor tissue, and PSMA-derived tumor burden is associated with severity of disease.

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Pilot Prospective Evaluation of (18)F-Alfatide II for Detection of Skeletal Metastases.

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Pilot Prospective Evaluation of (18)F-Alfatide II for Detection of Skeletal Metastases.

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