Detection of apoptosis by PET/CT with the diethyl ester of [18F]ML-10 and fluorescence imaging with a dansyl analogue

Kadirvel, Manikandan; Fairclough, Michael; Cawthorne, Christopher; Rowling, Emily J.; Babur, Muhammad; McMahon, Adam; Birkket, Paul; Smigova, Alison; Freeman, Sally; Williams, Kaye J.; Brown, Gavin

doi:10.1016/j.bmc.2013.11.019

Cited by 15 publications

(5 citation statements)

References 21 publications

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“…The current nucleophilic fluorination was applied for the synthesis of precursors for fluoroethyl L-tyrosine (FET) [63] and 2-(5-fluoropentyl)-2-methyl malonic acid (FPMA or ML-10) [64,65]. The 18 F isotopomer of FET [66] is used as a tumor imaging agent while and 18 F isotopomer of ML-10 [67,68] is used as apoptosis imaging agent [69][70][71].…”

Section: Resultsmentioning

confidence: 99%

Catalytic nucleophilic fluorination by an imidazolium ionic liquid possessing trialkylphosphine oxide functionality

Paramanik

Singh

Mukhopadhyay

et al. 2015

Journal of Fluorine Chemistry

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Section: Resultsmentioning

confidence: 99%

Catalytic nucleophilic fluorination by an imidazolium ionic liquid possessing trialkylphosphine oxide functionality

Paramanik

Singh

Mukhopadhyay

et al. 2015

Journal of Fluorine Chemistry

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“…In vivo, [ 18 F]ML-10 distribution results were comparable to those obtained in humans with a very rapid clearance from non-target organs and a urinary elimination [19,24]. Compared to other radiotracers targeting apoptosis (radiolabeled annexin V and Caspase3 radiolabeled), [ 18 F]ML-10 PET presented a rapid distribution due to its low molecular weight, which allowed early tumor imaging after intravenous administration.…”

Section: Discussionmentioning

confidence: 55%

[18F]ML-10 PET imaging fails to assess early response to neoadjuvant chemotherapy in a preclinical model of triple negative breast cancer

et al. 2020

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Purpose: Pathological complete response to the neoadjuvant therapy (NAT) for triple negative breast cancer (TNBC) is predictive of prolonged patient survival. Methods for early evaluation of NAT efficiency are still needed, in order to rapidly adjust the therapeutic strategy in case of initial non-response. One option for this is molecular imaging of apoptosis induced by chemotherapy. Therefore, we investigated the capacity of [ 18 F]ML-10 PET imaging, an apoptosis radiotracer, to detect tumor cell apoptosis and early predict the therapeutic response of human TNBC.Results: Initially, the induction of apoptosis by different therapies was quantified. We confirmed, in vitro, that paclitaxel or epirubicin, the fundamental cytotoxic drugs for breast cancer, induce apoptosis in TNBC cell lines. Exposure of TNBC models MDA-MB-231 and MDA-MB-468 to these drugs induced a significant increase (p < 0.01) of the apoptotic hallmarks: DNA fragmentation, membrane phospholipid scrambling, and PARP activation. Secondarily, apoptotic fraction was compared to the intracellular accumulation of the radiotracer. [ 18 F]ML-10 accumulated in the apoptotic cells after 72 h of treatment by paclitaxel in vitro; this accumulation positively correlated with the apoptotic fraction. In vivo, [ 18 F]ML-10 was rapidly cleared from the nontarget organs and mainly eliminated by the kidneys. Comparison of the in vivo [ 18 F]FDG, [ 18 F]FMISO, and [ 18 F]ML-10 uptakes revealed that the tumor accumulation of [ 18 F]ML-10 was directly related to the tumor hypoxia level. Finally, after the in vivo treatment of TNBC murine xenografts by paclitaxel, apoptosis was well induced, as demonstrated by the cleaved caspase-3 levels; however, no significant increase of [ 18 F]ML-10 accumulation in the tumors was observed, either on day 3 or day 6 after the end of the treatment.Conclusions: These results highlighted that PET imaging using [ 18 F]ML-10 allows the visualization of apoptotic cells in TNBC models. Nevertheless, the increase of the chemotherapy-induced apoptotic response when using paclitaxel could not be assessed using this radiotracer in our mouse model.

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“…Different preclinical and clinical studies have demonstrated that 18 F-ML-10 has potential as a PET agent to detect tumor apoptosis using PET imaging. 23,[28][29][30] However, a major challenge to apoptosis imaging includes the need to specifically image a downstream signal from apoptosis. Another significant challenge is that apoptosis is a transient process of relatively short duration between the time of initiation and ultimate cell death.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Evaluation of ¹⁸F-ML-10 to Determine Timing of Apoptotic Response to Chemotherapy in Solid Tumors

et al. 2017

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Purpose:We investigated 2-(5-fluoro-pentyl)-2-methyl-malonic acid (18F-ML-10) positron emission tomography (PET) imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model.Procedures:BALB/c nude mice (4-8 weeks old) were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2). Small animal 18F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy. Using regions of interest around tumors, 18F-ML-10 uptake change was measured as %ID/g and uptake relative to liver. Terminal Uridine Nick-End Labeling (TUNEL) immunohistochemistry assay was performed using tumor samples of baseline and on days 1, 3, and 7 posttreatment.Results:Treated mice demonstrated increased 18F-ML-10 uptake compared to baseline and controls, and 10 of 13 mice showed tumor volume decreases. All control mice showed tumor volume increases. Tumor-to-liver (T/L) ratios from the control group mice did not show significant change from baseline (P > .05); however, T/L ratios of the treatment group showed significant 18F-ML-10 uptake differences from baseline compared to days 3 and 7 posttreatment (P < .05), but no significant difference at 1 day posttreatment.Conclusion:2-(5-Fluoro-pentyl)-2-methyl-malonic acid PET imaging has the potential for early assessment of treatment-induced apoptosis. Timing and image analysis strategies may require optimization, depending on the type of tumor and cancer treatment.

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Detection of apoptosis by PET/CT with the diethyl ester of [18F]ML-10 and fluorescence imaging with a dansyl analogue

Cited by 15 publications

References 21 publications

Catalytic nucleophilic fluorination by an imidazolium ionic liquid possessing trialkylphosphine oxide functionality

Catalytic nucleophilic fluorination by an imidazolium ionic liquid possessing trialkylphosphine oxide functionality

[18F]ML-10 PET imaging fails to assess early response to neoadjuvant chemotherapy in a preclinical model of triple negative breast cancer

Preclinical Evaluation of ¹⁸F-ML-10 to Determine Timing of Apoptotic Response to Chemotherapy in Solid Tumors

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Detection of apoptosis by PET/CT with the diethyl ester of [18F]ML-10 and fluorescence imaging with a dansyl analogue

Cited by 15 publications

References 21 publications

Catalytic nucleophilic fluorination by an imidazolium ionic liquid possessing trialkylphosphine oxide functionality

Catalytic nucleophilic fluorination by an imidazolium ionic liquid possessing trialkylphosphine oxide functionality

[18F]ML-10 PET imaging fails to assess early response to neoadjuvant chemotherapy in a preclinical model of triple negative breast cancer

Preclinical Evaluation of 18F-ML-10 to Determine Timing of Apoptotic Response to Chemotherapy in Solid Tumors

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Preclinical Evaluation of ¹⁸F-ML-10 to Determine Timing of Apoptotic Response to Chemotherapy in Solid Tumors