Imaging of angiogenesis in metastatic breast cancer by positron emission tomography (PET) using [18F]AH11585, an [18F]- labeled alphaVbeta3 (αvβ3) peptide

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14067-14067
Author(s):  
L. M. Kenny ◽  
E. Aboagye ◽  
P. S. Cohen ◽  
M. Miller ◽  
F. Turkheimer ◽  
...  

14067 Background: In vivo imaging of avβ3 expression in tumors and tumor endothelial cells may be a useful biomarker of angiogenesis. [18F]AH11585 is a novel peptide containing an Arginine-Glycine-Aspartic Acid (RGD) motif that binds to avβ3 with high affinity designed for use in PET studies. Methods: 7 patients with metastatic breast cancer (aged 37–68 years) received intravenous injections of [18F]AH11585 and were scanned dynamically by PET over 61.5 mins. Radioactivity concentrations, derived from regions of interest placed on tumour and normal tissues, were analysed mathematically to determine the net irreversible uptake (Ki), fractional retention (FRT) and standardized uptake at 56.5min (SUV) of the radiotracer. Computed tomography (CT) was performed within 4 weeks of the scan. Results: Tumor lesions were clearly visible on PET images in 6/7 patients. In one patient with a palpable supraclavicular lymph node not visible on CT, we were unsure if a hyperintense region visible by PET was tumor. In total 18/19 tumor lesions were identified on both PET and corresponding CT images. Tumors in areas of low background were hyperintense (lung, bone, breast) whereas those in areas of high background were hypointense regions (liver). Tumors with central necrosis showed high uptake of [18F]AH11585 around the periphery only. Mathematical analysis demonstrated irreversible retention of [18F]AH11585 in tumors. [18F]AH11585-PET discriminated between non-liver lesions (n=10) and normal tissues: Ki (p=0.002), FRT (p=0.0039), SUV (p=0.002). Corresponding comparisons for liver lesions (n=8) were significant for FRT (p=0.0078) and SUV (p=0.0078) only. Conclusions: [18F]AH11585 PET is a promisng method for in vivo imaging of avβ3 integrin expression in metastatic breast cancer. No significant financial relationships to disclose.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mariane Le Fur ◽  
Alana Ross ◽  
Pamela Pantazopoulos ◽  
Nicholas Rotile ◽  
Iris Zhou ◽  
...  

Abstract Background In our earlier work, we identified microRNA-10b (miR10b) as a master regulator of the viability of metastatic tumor cells. This knowledge allowed us to design a miR10b-targeted therapeutic consisting of an anti-miR10b antagomir conjugated to ultrasmall iron oxide nanoparticles (MN), termed MN-anti-miR10b. In mouse models of breast cancer, we demonstrated that MN-anti-miR10b caused durable regressions of established metastases with no evidence of systemic toxicity. As a first step towards translating MN-anti-miR10b for the treatment of metastatic breast cancer, we needed to determine if MN-anti-miR10b, which is so effective in mice, will also accumulate in human metastases. Results In this study, we devised a method to efficiently radiolabel MN-anti-miR10b with Cu-64 (64Cu) and evaluated the pharmacokinetics and biodistribution of the radiolabeled product at two different doses: a therapeutic dose, referred to as macrodose, corresponding to 64Cu-MN-anti-miR10b co-injected with non-labeled MN-anti-miR10b, and a tracer-level dose of 64Cu-MN-anti-miR10b, referred to as microdose. In addition, we evaluated the uptake of 64Cu-MN-anti-miR10b by metastatic lesions using both in vivo and ex vivo positron emission tomography–magnetic resonance imaging (PET–MRI). A comparable distribution of the therapeutic was observed after administration of a microdose or macrodose. Uptake of the therapeutic by metastatic lymph nodes, lungs, and bone was also demonstrated by PET–MRI with a significantly higher PET signal than in the same organs devoid of metastatic lesions. Conclusion Our results demonstrate that PET–MRI following a microdose injection of the agent will accurately reflect the innate biodistribution of the therapeutic. The tools developed in the present study lay the groundwork for the clinical testing of MN-anti-miR10b and other similar therapeutics in patients with cancer.


2016 ◽  
Vol 76 (18) ◽  
pp. 5209-5218 ◽  
Author(s):  
Shreyas S. Rao ◽  
Grace G. Bushnell ◽  
Samira M. Azarin ◽  
Graham Spicer ◽  
Brian A. Aguado ◽  
...  

2021 ◽  
pp. 600-614
Author(s):  
Jennifer L. Caswell-Jin ◽  
Alison Callahan ◽  
Natasha Purington ◽  
Summer S. Han ◽  
Haruka Itakura ◽  
...  

PURPOSE Treatment and monitoring options for patients with metastatic breast cancer (MBC) are increasing, but little is known about variability in care. We sought to improve understanding of MBC care and its correlates by analyzing real-world claims data using a search engine with a novel query language to enable temporal electronic phenotyping. METHODS Using the Advanced Cohort Engine, we identified 6,180 women who met criteria for having estrogen receptor–positive, human epidermal growth factor receptor 2–negative MBC from IBM MarketScan US insurance claims (2007-2014). We characterized treatment, monitoring, and hospice usage, along with clinical and nonclinical factors affecting care. RESULTS We observed wide variability in treatment modality and monitoring across patients and geography. Most women received first-recorded therapy with endocrine (67%) versus chemotherapy, underwent more computed tomography (CT) (76%) than positron emission tomography-CT, and were monitored using tumor markers (58%). Nearly half (46%) met criteria for aggressive disease, which were associated with receiving chemotherapy first, monitoring primarily with CT, and more frequent imaging. Older age was associated with endocrine therapy first, less frequent imaging, and less use of tumor markers. After controlling for clinical factors, care strategies varied significantly by nonclinical factors (median regional income with first-recorded therapy and imaging type, geographic region with these and with imaging frequency and use of tumor markers; P < .0001). CONCLUSION Variability in US MBC care is explained by patient and disease factors and by nonclinical factors such as geographic region, suggesting that treatment decisions are influenced by local practice patterns and/or resources. A search engine designed to express complex electronic phenotypes from longitudinal patient records enables the identification of variability in patient care, helping to define disparities and areas for improvement.


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