Monitoring fluoropyrimidine metabolism in solid tumors with in vivo 19F magnetic resonance spectroscopy

Laarhoven, Hanneke W. M. van; Punt, Cornelis J.A.; Kamm, Y.J.L.; Heerschap, Arend

doi:10.1016/j.critrevonc.2005.03.009

Cited by 29 publications

(20 citation statements)

References 116 publications

(141 reference statements)

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“…The in vivo uptake and retention of fluorinated drugs in human liver can be measured non-invasively by means of 19 F MR spectroscopy ( 19 F MRS) (13). It has been suggested that an increased half-life of FU in the tumor as measured by 19 F MRS compared with the half-life of FU in blood, so-called tumor trapping, correlates with the response to FU therapy (14).…”

Section: Introductionmentioning

confidence: 99%

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Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium‐DTPA‐enhanced MRI and localized ¹⁹F MRS pharmacokinetic studies of 5‐fluorouracil

et al. 2006

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Systemic chemotherapy is effective in only a subset of patients with metastasized colorectal cancer. Therefore, early selection of patients who are most likely to benefit from chemotherapy is desirable. Response to treatment may be determined by the delivery of the drug to the tumor, retention of the drug in the tumor and by the amount of intracellular uptake, metabolic activation and catabolism, as well as other factors. The first aim of this study was to investigate the predictive value of DCE-MRI with the contrast agent Gd-DTPA for tumor response to first-line chemotherapy in patients with liver metastases of colorectal cancer. The second aim was to investigate the predictive value of 5-fluorouracil (FU) uptake, retention and catabolism as measured by localized (19)F MRS for tumor response to FU therapy. Since FU uptake, retention and metabolism may depend on tumor vascularization, the relationship between (19)F MRS and the DCE-MRI parameters k(ep), K(trans) and v(e) was also examined (1). In this study, 37 patients were included. The kinetic parameters of DCE-MRI, k(ep), K(trans) and v(e), before start of treatment did not predict tumor response after 2 months, suggesting that the delivery of chemotherapy by tumor vasculature is not a major factor determining response in first-line treatment. No evident correlations between (19)F MRS parameters and tumor response were found. This suggests that in liver metastases that are not selected on the basis of their tumor diameter, FU uptake and catabolism are not limiting factors for response. The transfer constant K(trans), as measured by DCE-MRI before start of treatment, was negatively correlated with FU half-life in the liver metastases, which suggests that, in metastases with a larger tumor blood flow or permeability surface area product, FU is rapidly washed out from the tumor.

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Section: Introductionmentioning

confidence: 99%

“…F MRS is a potentially powerful tool for the in vivo monitoring of fluorinated drugs (13). However, its clinical application is hampered by the relatively low SNR of 19 F MR spectra owing to low tissue concentration of the drugs (22).…”

mentioning

confidence: 99%

Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium‐DTPA‐enhanced MRI and localized ¹⁹F MRS pharmacokinetic studies of 5‐fluorouracil

et al. 2006

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“…These methods are a powerful means of repeatedly investigating the target tissue, e.g., tumor vasculature and hypoxia, metabolism, proliferation, and drug pharmacokinetics (5)(6)(7)(8). All these methods have been used as earlyresponse markers (5)(6)(7)9), but sparser clinical data suggest they could also be used as stratifiers, e.g., IFP was identified as an independent prognostic indicator in cervical cancer (10) and high tumor vascularity (K trans ) was associated with a better response to sorafenib in renal cancer (11).…”

mentioning

confidence: 99%

“…All these methods have been used as earlyresponse markers (5)(6)(7)9), but sparser clinical data suggest they could also be used as stratifiers, e.g., IFP was identified as an independent prognostic indicator in cervical cancer (10) and high tumor vascularity (K trans ) was associated with a better response to sorafenib in renal cancer (11). Nevertheless, these methods remain less than optimal because of one or more of the following: (a) complex and expensive chemistry, (b) low sensitivity, (c) nonquantitative, (d) require injections and modeling, (e) not applicable to all indications, and (f) add significant time to a protocol.…”

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confidence: 99%

Quantified Tumor T1 Is a Generic Early-Response Imaging Biomarker for Chemotherapy Reflecting Cell Viability

McSheehy

Weidensteiner

Cannet

et al. 2010

Clinical Cancer Research

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Purpose: Identification of a generic response biomarker by comparison of chemotherapeutics with different action mechanisms on several noninvasive biomarkers in experimental tumor models.Experimental Design: The spin-lattice relaxation time of water protons (T 1 ) was quantified using an inversion recovery-TrueFISP magnetic resonance imaging method in eight different experimental tumor models before and after treatment at several different time points with five different chemotherapeutics. Effects on T 1 were compared with other minimally invasive biomarkers including vascular parameters, apparent diffusion coefficient, and interstitial fluid pressure, and were correlated with efficacy at the endpoint and histologic parameters.Results: In all cases, successful chemotherapy significantly lowered tumor T 1 compared with vehicle and the fractional change in T 1 (ΔT 1 ) correlated with the eventual change in tumor size (range: r 2 = 0.21, P < 0.05 to r 2 = 0.73, P < 0.0001), except for models specifically resistant to that drug. In RIF-1 tumors, interstitial fluid pressure was decreased, but apparent diffusion coefficient and permeability increased in response to the microtubule stabilizer patupilone and 5-fluorouracil. Although ΔT 1 was small (maximum of −20%), the variability was very low (5%) compared with other magnetic resonance imaging methods (24-48%). Analyses ex vivo showed unchanged necrosis, increased apoptosis, and decreased %Ki67 and total choline, but only Ki67 and choline correlated with ΔT 1 . Correlation of Ki67 and ΔT 1 were observed in other models using patupilone, paclitaxel, a VEGF-R inhibitor, and the mammalian target of rapamycin inhibitor everolimus. Conclusions: These results suggest that a decrease in tumor T 1 reflects hypocellularity and is a generic marker of response. The speed and robustness of the method should facilitate its use in clinical trials. Clin Cancer Res; 16(1); 212-25. ©2010 AACR.

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“…The signals of a few endogenous metabolites can be observed and until now in a few cases only the fate of a drug in the target organ could be monitored using MRS. For instance, 19 F MRS has been successfully applied to assess the pharmacokinetics of fluorinated drugs, [154][155][156][157][158] and 13 C MRS to detect the distribution of 13 C labeled compounds in tumors. 159,160 The presence of metabolic (anabolic and/or catabolic) products of anti-neoplastic drugs has also been assessed in vivo using proton (iproplatin 161 ), 19 F (5-flurouracil 162,163 ) and 31 P MRS techniques (ifosfamide, 164,165 cyclophosphamide 165 ).…”

Section: In Vivo Magnetic Resonance Spectroscopy (Mrs)mentioning

confidence: 99%

Magnetic Resonance Methods and Applications in Pharmaceutical Research

Rodríguez

Pérez-Rial

Gonzáléz-Jiménez

et al. 2008

Journal of Pharmaceutical Sciences

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Monitoring fluoropyrimidine metabolism in solid tumors with in vivo 19F magnetic resonance spectroscopy

Cited by 29 publications

References 116 publications

Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium‐DTPA‐enhanced MRI and localized ¹⁹F MRS pharmacokinetic studies of 5‐fluorouracil

Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium‐DTPA‐enhanced MRI and localized ¹⁹F MRS pharmacokinetic studies of 5‐fluorouracil

Quantified Tumor T1 Is a Generic Early-Response Imaging Biomarker for Chemotherapy Reflecting Cell Viability

Magnetic Resonance Methods and Applications in Pharmaceutical Research

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Monitoring fluoropyrimidine metabolism in solid tumors with in vivo 19F magnetic resonance spectroscopy

Cited by 29 publications

References 116 publications

Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium‐DTPA‐enhanced MRI and localized 19F MRS pharmacokinetic studies of 5‐fluorouracil

Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium‐DTPA‐enhanced MRI and localized 19F MRS pharmacokinetic studies of 5‐fluorouracil

Quantified Tumor T1 Is a Generic Early-Response Imaging Biomarker for Chemotherapy Reflecting Cell Viability

Magnetic Resonance Methods and Applications in Pharmaceutical Research

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Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium‐DTPA‐enhanced MRI and localized ¹⁹F MRS pharmacokinetic studies of 5‐fluorouracil

Prediction of chemotherapeutic response of colorectal liver metastases with dynamic gadolinium‐DTPA‐enhanced MRI and localized ¹⁹F MRS pharmacokinetic studies of 5‐fluorouracil