Evaluation of [18F]gefitinib as a molecular imaging probe for the assessment of the epidermal growth factor receptor status in malignant tumors

Su, Helen C.; Seimbille, Yann; Ferl, Gregory Z.; Bodenstein, Claudia; Fueger, Barbara J.; Kim, Kevin J.; Hsu, Yu-Tien; Dubinett, Steven M.; Phelps, Michael E.; Czernin, Johannes; Weber, Wolfgang

doi:10.1007/s00259-007-0636-6

Cited by 97 publications

(87 citation statements)

References 31 publications

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“…Reversible TKI agent gefitinib was labeled with 18 F (t 1/2 = 110 min) to image the EGFR status of different cancer cells. However it was discovered that [ 18 F]-gefitinib uptake did not correlate with EGFR expression levels due to high non-specific cellular uptake (Su et al, 2008). This finding is in agreement with other studies showing that most reversible TKIs were inadequate for in vivo imaging despite impressive in vitro profile, including high affinity and specificity toward EGFR.…”

Section: Tki Derivativessupporting

confidence: 81%

Targeting EGFR and HER2 for Molecular Imaging of Cancer

Gong¹,

Sampath²,

Kovar³

et al. 2012

Molecular Imaging

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Section: Tki Derivativessupporting

confidence: 81%

Targeting EGFR and HER2 for Molecular Imaging of Cancer

Gong¹,

Sampath²,

Kovar³

et al. 2012

Molecular Imaging

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“…However, they can only detect the level of EGFR expression on the cell membrane; they cannot detect intracellular TK activity directly or determine the status of the EGFR signaling pathway accurately. Other quinazoline derivatives, including 18 F-gefitinib, were previously demonstrated to be candidates for EGFR imaging as well (24)(25)(26). However, rapid metabolism and nonspecific binding to the target receptor kinase made most of these agents ineffective as tracers for EGFR imaging, although some in vitro experiments indicated efficacy.…”

Section: Discussionmentioning

confidence: 99%

PET-Based Biodistribution and Radiation Dosimetry of Epidermal Growth Factor Receptor–Selective Tracer ¹¹C-PD153035 in Humans

Liu¹,

Li²,

Li³

et al. 2009

J Nucl Med

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The present study estimated the biodistribution and radiationabsorbed dose of epidermal growth factor receptor (EGFR) radioligand 11 C-PD153035 in whole-body PET examinations of healthy volunteers. Methods: Two-dimensional whole-body PET was performed on 9 subjects after injection of 11 C-PD153035 at 329.3 6 77.8 MBq (mean 6 SD). A total of 12 frames were acquired for approximately 90 min in 7 segments of the body. Regions of interest were drawn on PET images of source organs. Residence time was calculated as the area under the timeactivity curve. Radiation dosimetry was calculated from organ residence time by use of MIRDOSE3 software. Results: The renal and hepatobiliary systems played important roles in 11 C-PD153035 excretion from the body, accounting for the excretion of approximately 23% and 19% of the injected radioactivity, respectively. Blood-pool activity was only moderate and declined over time. Tracer accumulation in the lungs, bone marrow, and muscles was slight, resulting in low background activity in the chest. The organs with the highest radiation-absorbed doses were the urinary bladder and the gallbladder; the effective doses were 6.08E202 6 1.85E202 and 2.40E202 6 8.01E203 mGy/ MBq, respectively. The effective dose equivalent was 7.43E203 6 1.10E203 mSv/MBq, and the dose-limiting organ was the urinary bladder. Conclusion: On the basis of the estimated absorbed dose, 11 C-PD153035 displayed a favorable radiation dose profile in humans and therefore could be used in multiple PET examinations of the same subject per year. 11 C-PD153035 is a promising ligand for the investigation of EGFR in humans, especially in chest tumors such as non-small cell lung cancer.

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“…This biodistribution was similar to that of other EGFR-TK imaging agents. 14,19) One preferable characteristic is that 125 I-PHY uptake in blood, lung and brain is low, resulting in relatively high T/B and T/L ratios. This suggests that radioiodinated PHY is useful for imaging lung and brain tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Although 18 F-gefitinib was investigated to monitor EGFR expression and mutation status, tumor uptake was not correlated with EGFR expression levels and mutation status. 14) Development of various EGFR-TK imaging agents based exclusively on the anilinoquinazoline structure has been attempted for more than a decade, but further optimization of the properties of imaging agents with respect to high specificity to EGFR, selectivity to mutant types of kinase and high tumor uptake is required. [15][16][17][18][19][20] Thus, novel imaging agents to accurately detect EGFR-TK activity are needed in order to predict and monitor the therapeutic effects.…”

mentioning

confidence: 99%

Monitoring of Gefitinib Sensitivity with Radioiodinated PHY Based on EGFR Expression

Yoshimoto

Hirata

Kanai

et al. 2014

Biological & Pharmaceutical Bulletin

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Epidermal growth factor receptor (EGFR) is attractive target for tumor diagnosis and therapy, as it is specifically and abundantly expressed in tumor cells. EGFR-tyrosine kinase (TK) inhibitors such as gefitinib and erlotinib are widely used in the treatment of non-small cell lung cancer (NSCLC). In this study, we investigated whether radioiodinated 4-(3-iodo-phenoxy)-6,7-diethoxy-quinazoline (PHY), which is a candidate EGFR-TK imaging agent for single photon emission computed tomography (SPECT) is able to predict gefitinib sensitivity. We used four NSCLC cell lines-A549 (wild-type EGFR), H1650 (mutant EGFR; del E746_A750), H1975 (mutant EGFR; L858R, T790M) and H3255 (mutant EGFR; L858R)-and one epidermoid carcinoma cell line, A431 (wild-type EGFR). Cell proliferation assay and Western blotting revealed that A431 and H3255 with high EGFR expression showed high sensitivity to gefitinib. On the other hand, A549, H1650 and H1975 showed much lower sensitivity to gefitinib. The blocking study revealed that gefitinib decreased tumor uptake in 125 I-PHY in A431-bearing mice. Moreover, in vivo tumor uptake of 125 I-PHY was correlated with the IC 50 of gefitinib for cell proliferation. In the present study, tumor uptake of 125 I-PHY was correlated with the gefitinib sensitivity and this uptake was based on expression levels of EGFR, but not on mutation status. Although the mutation status is the most important factor for predicting gefitinib sensitivity, the abundant expression of EGFR is essential for therapy with EGFR-TK inhibitors. Therefore, radioiodinated PHY is a potential imaging agent to predict gefitinib sensitivity based on EGFR expression levels though further modifications of the imaging agent is needed to accurately estimate the mutation status.Key words tumor imaging; gefitinib; epidermal growth factor receptor tyrosine kinase; lung cancer; single photon emission computed tomography Epidermal growth factor receptor (EGFR) is overexpressed in a variety of tumors including non-small cell lung cancer (NSCLC), head and neck cancer, glioma and ovarian cancer.

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Evaluation of [18F]gefitinib as a molecular imaging probe for the assessment of the epidermal growth factor receptor status in malignant tumors

Cited by 97 publications

References 31 publications

Targeting EGFR and HER2 for Molecular Imaging of Cancer

Targeting EGFR and HER2 for Molecular Imaging of Cancer

PET-Based Biodistribution and Radiation Dosimetry of Epidermal Growth Factor Receptor–Selective Tracer ¹¹C-PD153035 in Humans

Monitoring of Gefitinib Sensitivity with Radioiodinated PHY Based on EGFR Expression

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Evaluation of [18F]gefitinib as a molecular imaging probe for the assessment of the epidermal growth factor receptor status in malignant tumors

Cited by 97 publications

References 31 publications

Targeting EGFR and HER2 for Molecular Imaging of Cancer

Targeting EGFR and HER2 for Molecular Imaging of Cancer

PET-Based Biodistribution and Radiation Dosimetry of Epidermal Growth Factor Receptor–Selective Tracer 11C-PD153035 in Humans

Monitoring of Gefitinib Sensitivity with Radioiodinated PHY Based on EGFR Expression

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PET-Based Biodistribution and Radiation Dosimetry of Epidermal Growth Factor Receptor–Selective Tracer ¹¹C-PD153035 in Humans