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Noninvasive blood-free full quantification of positron emission tomography radioligand binding.

ABSTRACT: Full quantification of a positron emission tomography (PET) radioligand binding to its target is preferred because it requires the fewest assumptions, but generally involves measuring the concentration of free radioligand in the arterial plasma by collecting blood samples from the subject's radial artery during the scan, and performing metabolite analysis. This invasive, costly procedure deters subjects' participation, and requires specialized staff and equipment. Simultaneous estimation (SIME) can fully quantify binding using only PET data from multiple brain regions and one individual anchor value, which is based on a single arterial blood sample. Drawing this sample can still be challenging in clinical settings, particularly when using simultaneous PET/magnetic resonance scanners. Here we propose a methodology for full quantification of binding that does not require any blood samples. The methodology substitutes the SIME blood-based anchor with a value predicted using multiple linear regression of noninvasive, easy-to-collect variables related to the radioligand blood concentration, and individual metabolism, such as injected dose, body mass index, or body surface area. As a study case, we show here the methodology in comparison to analysis with full arterial-line blood sampling in a cohort of 23 available scans with [(11)C]CUMI-101, a partial agonist of the serotonin 5-HT1A receptors.

SUBMITTER: Zanderigo F

PROVIDER: S-EPMC4294408 | biostudies-other | 2015 Jan

REPOSITORIES: biostudies-other

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Project description:Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. 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. Experimental design: Sixty-minute dynamic PET using [18F]FAl-NEB was performed in three xenograft tumor models including INS-1 rat insulinoma, UM-SCC-22B human head and neck carcinoma and U-87 MG human glioblastoma. Tumor vascular permeability was quantified by the difference of the slopes between tumor and blood time-activity curve (TACs, expressed as Ps ). The method was further substantiated by EB extraction and colorimetric assay and correlates with that calculated from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). The changes in tumor vasculature at different time points were assessed with NEB PET in U-87 MG and UM-SCC-22B tumor models after treatment with bevacizumab or doxorubicin. Result: The Ps values calculated from tumor and blood TACs from multiple time-point static images are consistent with those from dynamic images. Moreover, the Ps showed a positive and significant correlation with extracted EB concentration and KPS-MRI generated from DCE-MRI, which further confirmed the soundness of this methodology. The antiangiogenic effect of bevacizumab could be revealed by NEB PET in U-87 MG tumors as early as 8 hrs after therapy, demonstrated by a substantial decrease of Ps. On the contrary, there was no significant change of Ps in bevacizumab treated UM-SCC-22B tumors, compared with control group. However, the significant changes of Ps were overestimated in doxorubicin treated UM-SCC-22B tumors. Conclusions: We successfully developed a relatively convenient and novel strategy to evaluate vascular permeability and blood volume using NEB PET. This method will be advantageous in evaluating vascular permeability, promoting drug delivery, and monitoring tumor response to therapeutics that affect tumor angiogenesis.

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Noninvasive blood-free full quantification of positron emission tomography radioligand binding.

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