Breast MRI for Extent of Disease: Association of Demographic Factors and Biopsy Compliance on Surgical Decisions in Patients with BI-RADS 4 and 5 Findings.

BACKGROUND: The decision to pursue bilateral mastectomy without pathological confirmation of additional preoperative MRI lesions is likely multifactorial. We investigated the association of demographic factors and biopsy compliance following preoperative breast MRI with changes in surgical management in patients with newly diagnosed breast cancer. METHODS: A retrospective review of BI-RADS 4 and 5 MRIs performed across a health system from March 2018 to November 2021 for assessment of disease extent and preoperative planning. Patient characteristics, including demographics, Tyrer-Cuzick risk score, pathology from index cancer and biopsy of MRI findings, and pre- and post-MRI surgical plans were recorded. Analysis compared patients who underwent biopsy with those who did not. RESULTS: The final cohort included 323 patients who underwent a biopsy and 89 who did not. Of patients who underwent a biopsy, 144/323 (44.6%) had additional cancer diagnoses. MRI did not change management in 179/323 patients (55.4%) who underwent biopsy and in 44/89 patients (51.7%) who did not. Patients with a biopsy were more likely to have additional breast conservation surgery (P < .001) and patients without a biopsy were more likely to have a change in management to bilateral mastectomy P = .009). Patients without a biopsy who underwent a management change to bilateral mastectomy were significantly younger (47.2 vs 58.6; P < .001) and more likely to be white (P = .02) compared to those choosing bilateral mastectomy after biopsy. DISCUSSION: Biopsy compliance is associated with changes in surgical decisions, and younger, white women are more likely to pursue aggressive surgical management without definitive pathologic diagnoses.

Embracing nanomaterials' interactions with the innate immune system.

Immunotherapy has firmly established itself as a compelling avenue for treating disease. Although many clinically approved immunotherapeutics engage the adaptive immune system, therapeutically targeting the innate immune system remains much less explored. Nanomedicine offers a compelling opportunity for innate immune system engagement, as many nanomaterials inherently interact with myeloid cells (e.g., monocytes, macrophages, neutrophils, and dendritic cells) or can be functionalized to target their cell-surface receptors. Here, we provide a perspective on exploiting nanomaterials for innate immune system regulation. We focus on specific nanomaterial design parameters, including size, form, rigidity, charge, and surface decoration. Furthermore, we examine the potential of high-throughput screening and machine learning, while also providing recommendations for advancing the field. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition.

Trained immunity, a functional state of myeloid cells, has been proposed as a compelling immune-oncological target. Its efficient induction requires direct engagement of myeloid progenitors in the bone marrow. For this purpose, we developed a bone marrow-avid nanobiologic platform designed specifically to induce trained immunity. We established the potent anti-tumor capabilities of our lead candidate MTP10-HDL in a B16F10 mouse melanoma model. These anti-tumor effects result from trained immunity-induced myelopoiesis caused by epigenetic rewiring of multipotent progenitors in the bone marrow, which overcomes the immunosuppressive tumor microenvironment. Furthermore, MTP10-HDL nanotherapy potentiates checkpoint inhibition in this melanoma model refractory to anti-PD-1 and anti-CTLA-4 therapy. Finally, we determined MTP10-HDL's favorable biodistribution and safety profile in non-human primates. In conclusion, we show that rationally designed nanobiologics can promote trained immunity and elicit a durable anti-tumor response either as a monotherapy or in combination with checkpoint inhibitor drugs.

Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor 64Cu-Macrin in Mice, Rabbits, and Pigs.

BACKGROUND: Macrophages, innate immune cells that reside in all organs, defend the host against infection and injury. In the heart and vasculature, inflammatory macrophages also enhance tissue damage and propel cardiovascular diseases. METHODS: We here use in vivo positron emission tomography (PET) imaging, flow cytometry, and confocal microscopy to evaluate quantitative noninvasive assessment of cardiac, arterial, and pulmonary macrophages using the nanotracer 64Cu-Macrin-a 20-nm spherical dextran nanoparticle assembled from nontoxic polyglucose. RESULTS: PET imaging using 64Cu-Macrin faithfully reported accumulation of macrophages in the heart and lung of mice with myocardial infarction, sepsis, or pneumonia. Flow cytometry and confocal microscopy detected the near-infrared fluorescent version of the nanoparticle (VT680Macrin) primarily in tissue macrophages. In 5-day-old mice, 64Cu-Macrin PET imaging quantified physiologically more numerous cardiac macrophages. Upon intravenous administration of 64Cu-Macrin in rabbits and pigs, we detected heightened macrophage numbers in the infarcted myocardium, inflamed lung regions, and atherosclerotic plaques using a clinical PET/magnetic resonance imaging scanner. Toxicity studies in rats and human dosimetry estimates suggest that 64Cu-Macrin is safe for use in humans. CONCLUSIONS: Taken together, these results indicate 64Cu-Macrin could serve as a facile PET nanotracer to survey spatiotemporal macrophage dynamics during various physiological and pathological conditions. 64Cu-Macrin PET imaging could stage inflammatory cardiovascular disease activity, assist disease management, and serve as an imaging biomarker for emerging macrophage-targeted therapeutics.