RT Journal Article
SR Electronic
T1 Quantification of Tumor Vascular Permeability by Positron Emission Tomography with [18F]FAl-NEB
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 87
OP 87
VO 57
IS supplement 2
A1 Haojun Chen
A1 Xiao Tong
A1 Lixin Lang
A1 Dale Kiesewetter
A1 Hua Wu
A1 Gang Niu
A1 Xiaoyuan Chen
YR 2016
UL http://jnm.snmjournals.org/content/57/supplement_2/87.abstract
AB 87Objectives Disorganized vasculature with increased vascular permeability is one of the key features of malignant tumors. With an albumin binding, NOTA conjugated truncated Evan’s Blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET.Methods Sixty-minute dynamic PET using [18F]FAl-NEB was performed in several xenograft tumor models including INS-1 human insulinoma, SCC-UM-22B human head and neck carcinoma and U87MG human glioblastoma. Tumor vascular permeability was quantified by the difference of the slopes between tumor and blood time-activity curve (TAC, expressed as Kp). A two-compartment kinetic model was also used to describe the kinetics of [18F]FAl-NEB from plasma to interstitial fluid to substantiate the accuracy of Kp. Tumor-bearing mice were injected with Evans blue dye for EB extraction and colorimetric analysis, which is the gold standard for vascular permeability assay. After validating the method, Kp was used to evaluate the therapy response of U87MG (bevacizumab-responsive) and SCC-UM-22B (bevacizumab-resistant) tumors at days 1, 4, and 7 after bevacizumab administration. Result:Results The Kp values calculated from tumor and blood TACs from multiple time-point static images are consistent with those from dynamic images. Moreover, the Kp showed a positive and significant correlation with EB extraction, which further confirmed the soundness of this methodology. The antiangiogenic effect of bevacizumab could be detected by [18F]FAl-NEB PET in U87MG tumors as early as 1 day after therapy, demonstrated by a substantial decrease of Kp. On the contrary, there was no significant change of Kp in bevacizumab treated 22B tumors, compared with control group.Conclusions We successfully developed a relatively convenient and novel strategy to evaluate vascular permeability using [18F]FAl-NEB PET. This method will be helpful in evaluating tumor vascular permeability, promoting drug delivery and monitoring tumor response to therapeutics that involve angiogenesis. Figure 1. (A) The time-activity curves (TAC) for tumor and blood were fitted through linear regression. The angle between the tumor TAC and “shifted” blood TAC (dotted line) was used to quantify tumor vascular permeability. (B) Correlation of Kp measured by [18F]FAl-NEB PET with Evans blue amount measured by EB extraction method from a total of 36 tumors. (C) Representative maximum-intensity-projection (MIP) [18F]FAl-NEB PET images (2 h time point) acquired from control and bevacizumab-treated U87MG tumor mice at days 1, 4, and 7 post-treatment (n = 4/group). (D) PET Quantification of tumor vascular permeability (Kp) values in treated and control U87MG tumors. [asterisk]P < 0.05.