ANG1005 for breast cancer brain metastases: correlation between 18F-FLT–PET after first cycle and MRI in response assessment

O’Sullivan, Ciara C.; Lindenberg, Maria Liza; Bryla, Christine; Patronas, Nicholas J.; Peer, Cody J.; Amiri‐Kordestani, Laleh; Davarpanah, Nicole N.; Gonzalez, E. M.; Burotto, Mauricio; Choyke, Peter L.; Steinberg, Seth M.; Liewehr, David J.; Figg, William D.; Fojo, Tito; Balasubramaniam, Sanjeeve; Bates, Susan E.

doi:10.1007/s10549-016-3972-z

Cited by 33 publications

(24 citation statements)

References 31 publications

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“…Specific PET tracers such as the monoclonal antibody 89 Zrtrastuzumab are able to detect brain metastases in HER2 + breast cancer with a good uptake-to-background ratio (Dijkers et al, 2010). For breast cancer brain metastases treated with paclitaxel covalently linked to angiopep-2, changes in FLT PET correlated with MRI findings in a pilot study of 10 patients after a single treatment cycle and appeared to correlate with outcome (O’Sullivan et al, 2016). Extracranially, changes at 3 weeks in HER2+ patients correlate with tumor response at 8 weeks as measured by CT; this is not true for FDG PET (Gaykema et al, 2013).…”

Section: Early Response Markersmentioning

confidence: 89%

Brain metastases: neuroimaging

Pope

2018

Handbook of Clinical Neurology

154

130

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Magnetic resonance imaging (MRI) is the cornerstone for evaluating patients with brain masses such as primary and metastatic tumors. Important challenges in effectively detecting and diagnosing brain metastases and in accurately characterizing their subsequent response to treatment remain. These difficulties include discriminating metastases from potential mimics such as primary brain tumors and infection, detecting small metastases, and differentiating treatment response from tumor recurrence and progression. Optimal patient management could be benefited by improved and well-validated prognostic and predictive imaging markers, as well as early response markers to identify successful treatment prior to changes in tumor size. To address these fundamental needs, newer MRI techniques including diffusion and perfusion imaging, MR spectroscopy, and positron emission tomography (PET) tracers beyond traditionally used 18-fluorodeoxyglucose are the subject of extensive ongoing investigations, with several promising avenues of added value already identified. These newer techniques provide a wealth of physiologic and metabolic information that may supplement standard MR evaluation, by providing the ability to monitor and characterize cellularity, angiogenesis, perfusion, pH, hypoxia, metabolite concentrations, and other critical features of malignancy. This chapter reviews standard and advanced imaging of brain metastases provided by computed tomography, MRI, and amino acid PET, focusing on potential biomarkers that can serve as problem-solving tools in the clinical management of patients with brain metastases.

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Section: Early Response Markersmentioning

confidence: 89%

Brain metastases: neuroimaging

Pope

2018

Handbook of Clinical Neurology

154

130

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“…Both peptides have already been extensively used in efforts to deliver drugs to gliomas [25,27]. ANG1005, a drug composed of paclitaxel covalently linked to An2, has been tested against brain metastases of breast cancer [40,41] and is undergoing other clinical trials. PAPTP and PCARBTP efficiently killed cultured glioma and glioblastoma cell lines but did not affect tumor growth in an orthotopic murine model [16].…”

Section: Introductionmentioning

confidence: 99%

An Angiopep2-PAPTP Construct Overcomes the Blood-Brain Barrier. New Perspectives against Brain Tumors

et al. 2021

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A developing family of chemotherapeutics—derived from 5-(4-phenoxybutoxy)psoralen (PAP-1)—target mitochondrial potassium channel mtKv1.3 to selectively induce oxidative stress and death of diseased cells. The key to their effectiveness is the presence of a positively charged triphenylphosphonium group which drives their accumulation in the organelles. These compounds have proven their preclinical worth in murine models of cancers such as melanoma and pancreatic adenocarcinoma. In in vitro experiments they also efficiently killed glioblastoma cells, but in vivo they were powerless against orthotopic glioma because they were completely unable to overcome the blood-brain barrier. In an effort to improve brain delivery we have now coupled one of these promising compounds, PAPTP, to well-known cell-penetrating and brain-targeting peptides TAT48–61 and Angiopep-2. Coupling has been obtained by linking one of the phenyl groups of the triphenylphosphonium to the first amino acid of the peptide via a reversible carbamate ester bond. Both TAT48–61 and Angiopep-2 allowed the delivery of 0.3–0.4 nmoles of construct per gram of brain tissue upon intravenous (i.v.) injection of 5 µmoles/kg bw to mice. This is the first evidence of PAPTP delivery to the brain; the chemical strategy described here opens the possibility to conjugate PAPTP to small peptides in order to fine-tune tissue distribution of this interesting compound.

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“…As a marker of proliferation, FLT seems to be useful in further evaluating the activity of metastatic brain lesions. O’Sullivan et al reported that there was quite a good correlation between FLT and MRI in assessing treatment responses using a novel agent for breast cancer derived brain metastatic disease and demonstrated the supporting valuable contribution of FLT-PET in these cases [16]. Compared to FDG in head and neck cancer and thoracic malignancies, FLT seems to perform better in metastatic intracranial lesions [17,18].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Performance of 18F-Fluorothymidine Positron Emission Tomography/Computed Tomography (18F-FLT-PET/CT) in Metastatic Brain Lesions

et al. 2019

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18F-fluorothymidine (18F-FLT) is a radiolabeled thymidine analog that has been reported to help monitor tumor proliferation and has been studied in primary brain tumors; however, knowledge about 18F-FLT positron emission tomography/computed tomography (PET/CT) in metastatic brain lesions is limited. The purpose of this study is to evaluate the performance of 18F-FLT-PET/CT in metastatic brain lesions. A total of 20 PET/CT examinations (33 lesions) were included in the study. Semiquantitative analysis was performed: standard uptake value (SUV) with the utilization of SUVmax, tumor-to-background ratio (T/B), SUVpeak, SUV1cm3, SUV0.5cm3, SUV50%, SUV75%, PV50% (volume × SUV50%), and PV75% (volume × SUV75%) were calculated. Sensitivity, specificity, and accuracy for each parameter were calculated. Optimal cutoff values for each parameter were obtained. Using a receiver operating characteristic (ROC) curve analysis, the optimal cutoff values of SUVmax, T/B, and SUVpeak for discriminating active from non-active lesions were found to be 0.615, 4.21, and 0.425, respectively. In an ROC curve analysis, the area under the curve (AUC) is higher for SUVmax (p-value 0.017) compared to the rest of the parameters, while using optimal cutoff T/B shows the highest sensitivity and accuracy. PVs (proliferation × volumes) did not show any significance in discriminating positive from negative lesions. 18F-FLT-PET/CT can detect active metastatic brain lesions and may be used as a complementary tool. Further investigation should be performed.

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ANG1005 for breast cancer brain metastases: correlation between 18F-FLT–PET after first cycle and MRI in response assessment

Abstract: ANG1005 warrants further study in BCBM. Results demonstrated a moderately strong association between MRI and F-FLT-PET imaging.

Cited by 33 publications

References 31 publications

Brain metastases: neuroimaging

Brain metastases: neuroimaging

An Angiopep2-PAPTP Construct Overcomes the Blood-Brain Barrier. New Perspectives against Brain Tumors

Evaluation of the Performance of 18F-Fluorothymidine Positron Emission Tomography/Computed Tomography (18F-FLT-PET/CT) in Metastatic Brain Lesions

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