Positron Emission Tomography as a Method for Measuring Drug Delivery to Tumors in vivo: The Example of [11C]docetaxel

Veldt, Astrid A.M. van der; Smit, Egbert F.; Lammertsma, Adriaan A.

doi:10.3389/fonc.2013.00208

Cited by 29 publications

(27 citation statements)

References 33 publications

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“…Radiolabeled analogs or derivatives of taxanes such as [ 11 C]docetaxel and [ 18 F]fluoropaclitaxel have been evaluated in cancer patients as predictors of successful therapy (Kurdziel et al, 2011;van der Veldt et al, 2013avan der Veldt et al, , 2013b.…”

Section: Imaging Transporter Function In Cancer Tissuesmentioning

confidence: 99%

Imaging techniques to study drug transporter function in vivo

Tournier

Stieger

Langer

2018

Pharmacology & Therapeutics

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Transporter systems involved in the permeation of drugs and solutes across biological membranes are recognized as key determinants of pharmacokinetics. Typically, the action of membrane transporters on drug exposure to tissues in living organisms is inferred from invasive procedures, which cannot be applied in humans. In recent years, imaging methods have greatly progressed in terms of instruments, synthesis of novel imaging probes as well as tools for data analysis. Imaging allows pharmacokinetic parameters in different tissues and organs to be obtained in a non-invasive or minimally invasive way. The aim of this overview is to summarize the current status in the field of molecular imaging of drug transporters. The overview is focused on human studies, both for the characterization of transport systems for imaging agents as well as for the determination of drug pharmacokinetics, and makes reference to animal studies where necessary. We conclude that despite certain methodological limitations, imaging has a great potential to study transporters at work in humans and that imaging will become an important tool, not only in drug development but also in medicine. Imaging allows the mechanistic aspects of transport proteins to be studied, as well as elucidating the influence of genetic background, pathophysiological states and drug-drug interactions on the function of transporters involved in the disposition of drugs.

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Section: Imaging Transporter Function In Cancer Tissuesmentioning

confidence: 99%

Imaging techniques to study drug transporter function in vivo

Tournier

Stieger

Langer

2018

Pharmacology & Therapeutics

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“…Positron emission tomography is one method previously used to identify the optimal volume/concentration for intratumoral administration. 72 There are two major methods of transportation: the passive and active targeting. The active transportation is based on the ligand-receptor interaction, while in the passive transportation the diffusion of a compound within the tissue is based on its physical properties.…”

Section: Resultsmentioning

confidence: 99%

Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector–p53

et al. 2013

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Lung cancer still remains to be challenged by novel treatment modalities. Novel locally targeted routes of administration are a methodology to enhance treatment and reduce side effects. Intratumoral gene therapy is a method for local treatment and could be used either in early-stage lung cancer before surgery or at advanced stages as palliative care. Novel non-viral vectors are also in demand for efficient gene transfection to target local cancer tissue and at the same time protect the normal tissue. In the current study, C57BL/6 mice were divided into three groups: (a) control, (b) intravenous and (c) intatumoral gene therapy. The novel 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector (Ryujyu Science Corporation) was conjugated with plasmid pSicop53 from the company Addgene for the first time. The aim of the study was to evaluate the safety and efficacy of targeted gene therapy in a Lewis lung cancer model. Indeed, although the pharmacokinetics of the different administration modalities differs, the intratumoral administration presented increased survival and decreased distant metastasis. Intratumoral gene therapy could be considered as an efficient local therapy for lung cancer.

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“…Importantly, this [18F]FDG PET scan was acquired within 3 days after administration of the second cycle of chemotherapy. A study by van der Veldt et al [34] showed that bevacizumab reduces tumor perfusion and [11C] docetaxel uptake in NSCLC, which was accompanied by rapid reduction in circulating levels of VEGF. This decrease in tumor blood flow after bevacizumab administration may explain the lower uptake of FDG in the tumor.…”

Section: Discussionmentioning

confidence: 99%

[18F]FDG PET/CT-based response assessment of stage IV non-small cell lung cancer treated with paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches

Jong

Elmpt

Hoekstra

et al. 2016

Eur J Nucl Med Mol Imaging

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PurposeNitroglycerin (NTG) is a vasodilating drug, which increases tumor blood flow and consequently decreases hypoxia. Therefore, changes in [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG PET) uptake pattern may occur. In this analysis, we investigated the feasibility of [18F]FDG PET for response assessment to paclitaxel-carboplatin-bevacizumab (PCB) treatment with and without NTG patches. And we compared the [18F]FDG PET response assessment to RECIST response assessment and survival.MethodsA total of 223 stage IV non-small cell lung cancer (NSCLC) patients were included in a phase II study (NCT01171170) randomizing between PCB treatment with or without NTG patches. For 60 participating patients, a baseline and a second [18F]FDG PET/computed tomography (CT) scan, performed between day 22 and 24 after the start of treatment, were available. Tumor response was defined as a 30 % decrease in CT and PET parameters, and was compared to RECIST response at week 6. The predictive value of these assessments for progression free survival (PFS) and overall survival (OS) was assessed with and without NTG.ResultsA 30 % decrease in SUVpeak assessment identified more patients as responders compared to a 30 % decrease in CT diameter assessment (73 % vs. 18 %), however, this was not correlated to OS (SUVpeak30 p = 0.833; CTdiameter30 p = 0.557). Changes in PET parameters between the baseline and the second scan were not significantly different for the NTG group compared to the control group (p value range 0.159–0.634). The CT-based (part of the [18F]FDG PET/CT) parameters showed a significant difference between the baseline and the second scan for the NTG group compared to the control group (CT diameter decrease of 7 ± 23 % vs. 19 ± 14 %, p = 0.016, respectively).ConclusionsThe decrease in tumoral FDG uptake in advanced NSCLC patients treated with chemotherapy with and without NTG did not differ between both treatment arms. Early PET-based response assessment showed more tumor responders than CT-based response assessment (part of the [18F]FDG PET/CT); this was not correlated to survival. This might be due to timing of the [18F]FDG PET shortly after the bevacizumab infusion.

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Positron Emission Tomography as a Method for Measuring Drug Delivery to Tumors in vivo: The Example of [11C]docetaxel

Cited by 29 publications

References 33 publications

Imaging techniques to study drug transporter function in vivo

Imaging techniques to study drug transporter function in vivo

Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector–p53

[18F]FDG PET/CT-based response assessment of stage IV non-small cell lung cancer treated with paclitaxel-carboplatin-bevacizumab with or without nitroglycerin patches

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