[18F]ML-10 Imaging for Assessment of Apoptosis Response of Intracranial Tumor Early after Radiosurgery by PET/CT

Sun, Lu; Zhou, Kedi; Zhang, Xiaojun; Ju, Zhongjian; Qu, Baolin; Zhang, Zhizhong; Wang, Jin‐Yuan; Ling, Zhipei; Yu, Xin-guang; Zhang, Jinming; Pan, Longsheng

doi:10.1155/2018/9365174

Cited by 14 publications

(9 citation statements)

References 26 publications

(33 reference statements)

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“…All lesions studied were detected by 18 F-ML-10 PET and a highly significant correlation was found between early changes on the 18 F-ML-10 scans and later changes in tumour anatomical dimensions assessed using sequential MRI-imaging. Similar results were obtained by Sun et al in a study of 29 patients, diagnosed with intracranial tumours that underwent a cyberknife treatment at 14-24 Gy in 1-3 fractions, as well as a baseline and 48 h post-treatment 18 F-ML-10 PET scan [48]. It was found that malignant tumours tended to be more sensitive to the CK treatment but that the treatment outcome was not affected by the pre-CK apoptotic status of tumour cells, as assessed using 18 F-ML-1P PET.…”

Section: Cell Membrane Acidification Targeting Radioligandssupporting

confidence: 88%

Apoptosis Imaging in Oncology by Means of Positron Emission Tomography: A Review

Wiele

Ustmert

Spiegeleer

et al. 2021

IJMS

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To date, a wide variety of potential PET-apoptosis imaging radiopharmaceuticals targeting apoptosis-induced cell membrane asymmetry and acidification, as well as caspase 3 activation (substrates and inhibitors) have been developed with the purpose of rapidly assessing the response to treatment in cancer patients. Many of these probes were shown to specifically bind to their apoptotic target in vitro and their uptake to be enhanced in the in vivo-xenografted tumours in mice treated by means of chemotherapy, however, to a significantly variable degree. This may, in part, relate to the tumour model used given the fact that different tumour cell lines bear a different sensitivity to a similar chemotherapeutic agent, to differences in the chemotherapeutic concentration and exposure time, as well as to the different timing of imaging performed post-treatment. The best validated cell membrane acidification and caspase 3 targeting radioligands, respectively 18F-ML-10 from the Aposense family and the radiolabelled caspase 3 substrate 18F-CP18, have also been injected in healthy individuals and shown to bear favourable dosimetric and safety characteristics. However, in contrast to, for instance, the 99mTc-HYNIC-Annexin V, neither of both tracers was taken up to a significant degree by the bone marrow in the healthy individuals under study. Removal of white and red blood cells from the bone marrow through apoptosis plays a major role in the maintenance of hematopoietic cell homeostasis. The major apoptotic population in normal bone marrow are immature erythroblasts. While an accurate estimate of the number of immature erythroblasts undergoing apoptosis is not feasible due to their unknown clearance rate, their number is likely substantial given the ineffective quote of the erythropoietic process described in healthy subjects. Thus, the clinical value of both 18F-ML-10 and 18F-CP18 for apoptosis imaging in cancer patients, as suggested by a small number of subsequent clinical phase I/II trials in patients suffering from primary or secondary brain malignancies using 18F-ML-10 and in an ongoing trial in patients suffering from cancer of the ovaries using 18F-CP18, remains to be proven and warrants further investigation.

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Section: Cell Membrane Acidification Targeting Radioligandssupporting

confidence: 88%

Apoptosis Imaging in Oncology by Means of Positron Emission Tomography: A Review

Wiele

Ustmert

Spiegeleer

et al. 2021

IJMS

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“…Several small-molecule imaging probes that detect cell or mitochondrial membrane depolarisation and/or acidification of apoptotic cells have also been developed. In patients with intracranial tumours, the change in 18 F-ML-10 uptake from before to 48 h after CyberKnife stereotactic radiotherapy correlated with the decrease in tumour volume measured at 2–4 months after treatment [25]. Similar correlations have been made in patients with brain metastases imaged before and nine days after whole-brain radiotherapy [26].…”

Section: Imaging Apoptosis and Necrosismentioning

confidence: 73%

Emerging Functional Imaging Biomarkers of Tumour Responses to Radiotherapy

Campbell

Davis

Wilkinson

et al. 2019

Cancers

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Tumour responses to radiotherapy are currently primarily assessed by changes in size. Imaging permits non-invasive, whole-body assessment of tumour burden and guides treatment options for most tumours. However, in most tumours, changes in size are slow to manifest and can sometimes be difficult to interpret or misleading, potentially leading to prolonged durations of ineffective treatment and delays in changing therapy. Functional imaging techniques that monitor biological processes have the potential to detect tumour responses to treatment earlier and refine treatment options based on tumour biology rather than solely on size and staging. By considering the biological effects of radiotherapy, this review focusses on emerging functional imaging techniques with the potential to augment morphological imaging and serve as biomarkers of early response to radiotherapy.

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“…Indeed, this inflammation leads to two phenomena: an activation of the immune system which will induce an increase in blood flow and an acidification of the microenvironment due to the release of immune cells and cytokines [34]. As a consequence, precedent clinical trials used [ 18 F]ML-10 for PET imaging of apoptosis following radiotherapy treatments [21,35].…”

Section: Discussionmentioning

confidence: 99%

“…The [ 18 F]ML-10 radiotracer is highly stable in vivo and presents a rapid clearance from non-targeted organs and a favorable dosimetry profile [19]. Several clinical trials have recently evaluated [ 18 F]ML-10 for early detection of response to radiation therapy in patients with brain metastases [20,21]. In those studies, early treatmentinduced changes in the [ 18 F]ML-10 tumor accumulation were measured by voxel-based analysis and correlated with changes in anatomical dimensions, as visualized with magnetic resonance imaging (MRI).…”

Section: Introductionmentioning

confidence: 99%

[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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[18F]ML-10 Imaging for Assessment of Apoptosis Response of Intracranial Tumor Early after Radiosurgery by PET/CT

Cited by 14 publications

References 26 publications

Apoptosis Imaging in Oncology by Means of Positron Emission Tomography: A Review

Apoptosis Imaging in Oncology by Means of Positron Emission Tomography: A Review

Emerging Functional Imaging Biomarkers of Tumour Responses to Radiotherapy

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

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