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Practical approach for comparative analysis of multilesion molecular imaging using a semiautomated program for PET/CT.

ABSTRACT: We propose a standardized approach to quantitative molecular imaging (MI) in cancer patients with multiple lesions.Twenty patients with castration-resistant prostate cancer underwent (18)F-FDG and (18)F-16?-fluoro-5-dihydrotestosterone ((18)F-FDHT) PET/CT scans. Using a 5-point confidence scale, 2 readers interpreted coregistered scan sets on a workstation. Two hundred three sites per scan (specified in a lexicon) were reviewed. (18)F-FDG-positive lesion bookmarks were propagated onto (18)F-FDHT studies and then manually accepted or rejected. Discordance-positive (18)F-FDHT lesions were similarly bookmarked. Lesional SUV(max) was recorded. Tracer- and tissue-specific background correction factors were calculated via receiver-operating-characteristic analysis of 65 scan sets.Readers agreed on more than 99% of (18)F-FDG- and (18)F-FDHT-negative sites. Positive-site agreement was 83% and 85%, respectively. Consensus-lesion maximum standardized uptake value (SUV(max)) was highly reproducible (concordance correlation coefficient > 0.98). Receiver-operating-characteristic curves yielded 4 correction factors (SUV(max) 1.8-2.6). A novel scatterplot (Larson-Fox-Gonen plot) depicted tumor burden and change in SUV(max) for response assessments.Multilesion molecular imaging is optimized with a 5-step approach incorporating a confidence scale, site lexicon, semiautomated PET software, background correction, and Larson-Fox-Gonen graphing.

SUBMITTER: Fox JJ

PROVIDER: S-EPMC3409842 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Practical approach for comparative analysis of multilesion molecular imaging using a semiautomated program for PET/CT.

Fox Josef J JJ Autran-Blanc Estelle E Morris Michael J MJ Gavane Somali S Nehmeh Sadek S Van Nuffel André A Gönen Mithat M Schöder Heiko H Humm John L JL Scher Howard I HI Larson Steven M SM

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20111007 11

<h4>Unlabelled</h4>We propose a standardized approach to quantitative molecular imaging (MI) in cancer patients with multiple lesions.<h4>Methods</h4>Twenty patients with castration-resistant prostate cancer underwent (18)F-FDG and (18)F-16β-fluoro-5-dihydrotestosterone ((18)F-FDHT) PET/CT scans. Using a 5-point confidence scale, 2 readers interpreted coregistered scan sets on a workstation. Two hundred three sites per scan (specified in a lexicon) were reviewed. (18)F-FDG-positive lesion bookma ...[more]

PMID: 21984797

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Project description:UNLABELLED:Atherosclerosis is inherently an inflammatory process that is strongly affected by the chemokine-chemokine receptor axes regulating the trafficking of inflammatory cells at all stages of the disease. Of the chemokine receptor family, some specifically upregulated on macrophages play a critical role in plaque development and may have the potential to track plaque progression. However, the diagnostic potential of these chemokine receptors has not been fully realized. On the basis of our previous work using a broad-spectrum peptide antagonist imaging 8 chemokine receptors together, the purpose of this study was to develop a targeted nanoparticle for sensitive and specific detection of these chemokine receptors in both a mouse vascular injury model and a spontaneously developed mouse atherosclerosis model. METHODS:The viral macrophage inflammatory protein-II (vMIP-II) was conjugated to a biocompatible poly(methyl methacrylate)-core/polyethylene glycol-shell amphiphilic comblike nanoparticle through controlled conjugation and polymerization before radiolabeling with (64)Cu for PET imaging in an apolipoprotein E-deficient (ApoE(-/-)) mouse vascular injury model and a spontaneous ApoE(-/-) mouse atherosclerosis model. Histology, immunohistochemistry, and real-time reverse transcription polymerase chain reaction were performed to assess the plaque progression and upregulation of chemokine receptors. RESULTS:The chemokine receptor-targeted (64)Cu-vMIP-II-comb showed extended blood retention and improved biodistribution. PET imaging showed specific tracer accumulation at plaques in ApoE(-/-) mice, confirmed by competitive receptor blocking studies and assessment in wild-type mice. Histopathologic characterization showed the progression of plaque including size and macrophage population, corresponding to the elevated concentration of chemokine receptors and more importantly increased PET signals. CONCLUSION:This work provides a useful nanoplatform for sensitive and specific detection of chemokine receptors to assess plaque progression in mouse atherosclerosis models.

Project description:PurposeTracking cells in vivo using imaging can provide non-invasive information to understand the pharmacology, efficacy, and safety of novel cell therapies. Zirconium-89 (t1/2 = 78.4 h) has recently been used to synthesize [89Zr]Zr(oxinate)4 for cell tracking using positron emission tomography (PET). This work presents an in vitro approach to estimate the detection limit for in vivo PET imaging of Jurkat T cells directly labeled with [89Zr]Zr(oxinate)4 utilizing clinical PET/CT and PET/MRI.MethodsJurkat T cells were labeled with varying concentrations of [89Zr]Zr(oxinate)4 to generate different cell-specific activities (0.43-31.91 kBq/106 cells). Different concentrations of labeled cell suspensions (104, 105, and 106 cells) were seeded on 6-well plates and into a 3 × 3 cubic-well plate with 1 cm3 cubic wells as a gel matrix. Plates were imaged on clinical PET/CT and PET/MRI scanners for 30 min. The total activity in each well was determined by drawing volumes of interest over each well on PET images. The total cell-associated activity was measured using a well counter and correlated with imaging data. Simulations for non-specific signal were performed to model the effect of non-specific radioactivity on detection.ResultsUsing this in vitro model, the lowest cell number that could be visualized on 6-well plate images was 6.8 × 104, when the specific activity was 27.8 kBq/106 cells. For the 3 × 3 cubic-well, a plate of 3.3 × 104 cells could be detected on images with a specific activity of 15.4 kBq/106 cells.ConclusionThe results show the feasibility of detecting [89Zr]Zr(oxinate)4-labeled Jurkat T cells on clinical PET systems. The results provide a best-case scenario, as in vivo detection using PET/CT or PET/MRI will be affected by cell number, specific activity per cell, the density of cells within the target volume, and non-specific signal. This work has important implications for cell labeling studies in patients, particularly when using radiosensitive cells (e.g., T cells), which require detection of low cell numbers while minimizing radiation dose per cell.

Dataset Information

Practical approach for comparative analysis of multilesion molecular imaging using a semiautomated program for PET/CT.

Publications

Practical approach for comparative analysis of multilesion molecular imaging using a semiautomated program for PET/CT.

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