Molecular imaging in cancer treatment

Michalski, Mark; Chen, Xiaoyuan

doi:10.1007/s00259-010-1569-z

Cited by 74 publications

(82 citation statements)

References 173 publications

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“…For several malignancies, including colorectal cancer, 18 F-FDG PET/CT examination is today recommended for preoperative staging and detection of recurrence (3)(4)(5)(6), and there is growing research attention to expanding the use of 18 F-FDG PET/CT in evaluating the response of metastatic disease (7)(8)(9)(10). To create the reproducibility that is needed for comparison of response rates between trials, the use of 18 F-FDG PET/CT in the setting of metastatic disease requires a fundamental standardization and consensus on response quantification methodology (11)(12)(13). Otherwise, the potential benefit for patients and for anticancer drug development could be lost.…”

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confidence: 99%

Comparison of EORTC Criteria and PERCIST for PET/CT Response Evaluation of Patients with Metastatic Colorectal Cancer Treated with Irinotecan and Cetuximab

et al. 2013

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The study aim was to compare European Organization for Research and Treatment of Cancer (EORTC) criteria with PET Response Criteria in Solid Tumors (PERCIST) for response evaluation of patients with metastatic colorectal cancer treated with a combination of the chemotherapeutic drug irinotecan and the monoclonal antibody cetuximab. Methods: From 2006 to 2009, patients with metastatic colorectal cancer were prospectively included in a phase II trial evaluating the combination of irinotecan and cetuximab every second week, as third-line treatment. 18 F-FDG PET/CT was performed between 1 and 14 d before the first treatment and after every fourth treatment cycle until progression was identified by CT with Response Evaluation Criteria in Solid Tumors (RECIST). Response evaluation with 18 F-FDG PET/CT was retrospectively performed according to both EORTC criteria and PERCIST, classifying the patients into 4 response categories: complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). Individual best overall metabolic response (BOmR) was registered with both sets of criteria, as well as survival within response categories, and compared. Results: A total of 61 patients and 203 PET/CT scans were eligible for response evaluation. With EORTC criteria, 38 had PMR, 16 had SMD, and 7 had PMD as their BOmR. With PERCIST, 34 had PMR, 20 had SMD, and 7 had PMD as their BOmR. None of the patients had CMR. There was agreement between EORTC criteria and PERCIST in 87% of the patients, and the corresponding k-coefficient was 0.76. Disagreements were confined to PMR and SMD. Median overall survival (OS) in months with EORTC criteria was 14.2 in the PMR group and 7.2 in the combined SMD 1 PMD group. With PERCIST, it was 14.5 in the PMR group and 7.9 in the SMD 1 PMD group. Conclusion: Response evaluation with EORTC criteria and PERCIST gave similar responses and OS outcomes with good agreement on BOmR (k-coefficient, 0.76) and similar significant differences in median OS between response groups. Compared with EORTC criteria, we find PERCIST unambiguous because of clear definitions and therefore more straightforward to use.

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confidence: 99%

Comparison of EORTC Criteria and PERCIST for PET/CT Response Evaluation of Patients with Metastatic Colorectal Cancer Treated with Irinotecan and Cetuximab

et al. 2013

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“…VEGF/VEGFR antibodies have been labeled with various radioisotopes for the imaging of VEGFR expression in various disease models (20). For example, extracellular VEGF imaging was accomplished by coupling anti-VEGF monoclonal antibodies (bevacizumab, HuMV833) with 89 Zr (21,22), 111 In (23), and 124 I (24).…”

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confidence: 99%

A Tyrosine Kinase Inhibitor–Based High-Affinity PET Radiopharmaceutical Targets Vascular Endothelial Growth Factor Receptor

Jiang

et al. 2014

J Nucl Med

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Tyrosine kinase receptors including vascular endothelial growth factor receptor (VEGFR) have gained significant attention as pharmacologic targets. However, clinical evaluation of small-molecule drugs or biologics that target these pathways has so far yielded mixed results in a variety of solid tumors. The reasons for response variability remain unknown, including the temporal and spatial patterns of receptor tyrosine kinase expression. Methods to detect and quantify the presence of such cellular receptors would greatly facilitate drug development and therapy response assessment. We aimed to generate specific imaging agents as potential companion diagnostics that could also be used for targeted radionuclide therapy. Here, we report on the synthesis and initial preclinical performance of 64 Cu-labeled probes that were based on the kinase inhibitor already in clinical use, vandetanib (ZD6474), as a VEGFR-selective theranostic radiopharmaceutical. Methods: A monomeric (ZD-G1) and a dimeric (ZD-G2) derivative of ZD6474 were synthesized and conjugated with DOTA for chelation with 64 Cu to produce the probes 64 Cu-DOTA-ZD-G1 and 64 Cu-DOTA-ZD-G2. The binding affinity and specificity to VEGFR were measured using U-87 MG cells known to overexpress VEGFR. Small-animal PET and biodistribution studies were performed with 64 Cu-labeled probes (3-4 MBq) intravenously administered in U-87 MG tumor-bearing mice with or without coinjection of unlabeled ZD-G2 for up to 24 h after injection. Results: Receptor-binding assays yielded a mean equilibrium dissociation constant of 44.7 and 0.45 nM for monomeric and dimeric forms, respectively, indicating a synergistic effect in VEGFR affinity by multivalency. Small-animal PET/CT imaging showed rapid tumor accumulation of 64 Cu-DOTA-ZD-G2, with excellent tumor-to-normal tissue contrast by 24 h. Coinjection of the 64 Cu-DOTA-ZD-G2 with 50 nmol (60 μg) of nonradioactive ZD-G2 effectively blocked tumor uptake. Conclusion: A 64 Cu-labeled probe derived from an approved oncologic drug selective for VEGFR demonstrates excellent tumor targeting, particularly for the dimeric form. The multivalent probe yielded a 100-fold improvement in receptor affinity while maintaining pharmacokinetic and biodistribution properties well suited for PET imaging in our preclinical model. These results indicate that a clinically relevant theranostic platform can be rapidly developed from known small molecules that target key cellular receptors.

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“…It can also reveal more in-depth information on the boilogy of tissue cells that are closer to the essence of life, including those involved in processes such as metabolism, proliferation, angiogenesis and gene expression. The use of molecular imaging not only helps improve the accuracy of early diagnosis of a tumor, but can also provide the necessary early clinical evidence of metastasis and prediction of efficacy of a particular therapy at the molecular level [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Distribution of c-erbB2 Antisense Probe Labeled with Superparamagnetic Iron Oxide Nanoparticles in the Major Organs of Mice on MR Imaging

Wen¹,

Liu²,

He³

et al. 2013

ANP

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Background: The aim of this study was to investigate the distribution of the c-erbB2 antisense probe labeled with superparamagnetic iron oxide nanoparticles in the major organs of mice by MR imaging. Methods: Sixty BALB/c mice were randomly divided into experimental and control groups. MR scans were performed in each mouse of the experimental group at five different time points (10, 30, 60, 180 and 360 min) after injection of the antisense probe. The signal from each major organ (liver, spleen, heart, kidney and muscle tissue) in comparison with the background signal (signal to noise ratio) was determined at each time point as a measure of the distribution of the antisense probe. Six control mice were killed at each of the same time points and the organs immediately removed for determination of their iron content. Results: After injection of the antisense probe, the highest enrichment of the probe was seen in the spleen, reaching a peak at 180 min, followed by the liver, muscle, heart and kidney. Conclusions: MR imaging can visualize the distribution of c-erbB2 antisense probe labeled with superparamagnetic iron oxide nanoparticles in the major organs of mice, and this may provide the basis for further in vivo studies of MR imaging time and dose selection.

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Molecular imaging in cancer treatment

Cited by 74 publications

References 173 publications

Comparison of EORTC Criteria and PERCIST for PET/CT Response Evaluation of Patients with Metastatic Colorectal Cancer Treated with Irinotecan and Cetuximab

Comparison of EORTC Criteria and PERCIST for PET/CT Response Evaluation of Patients with Metastatic Colorectal Cancer Treated with Irinotecan and Cetuximab

A Tyrosine Kinase Inhibitor–Based High-Affinity PET Radiopharmaceutical Targets Vascular Endothelial Growth Factor Receptor

Distribution of c-erbB2 Antisense Probe Labeled with Superparamagnetic Iron Oxide Nanoparticles in the Major Organs of Mice on MR Imaging

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