The principle of magnetic drug targeting, wherein therapy is attached to magnetically responsive carriers and magnetic fields are used to direct that therapy to disease locations, has been around for nearly two decades. Yet our ability to safely and effectively direct therapy to where it needs to go, for instance to deep tissue targets, remains limited. To date, magnetic targeting methods have not yet passed regulatory approval or reached clinical use. Below we outline key challenges to magnetic targeting, which include designing and selecting magnetic carriers for specific clinical indications, safely and effectively reaching targets behind tissue and anatomical barriers, real-time carrier imaging, and magnet design and control for deep and precise targeting. Addressing these challenges will require interactions across disciplines. Nanofabricators and chemists should work with biologists, mathematicians and engineers to better understand how carriers move through live tissues and how to optimize carrier and magnet designs to better direct therapy to disease targets. Clinicians should be involved early on and throughout the whole process to ensure the methods that are being developed meet a compelling clinical need and will be practical in a clinical setting. Our hope is that highlighting these challenges will help researchers translate magnetic drug targeting from a novel concept to a clinically-available treatment that can put therapy where it needs to go in human patients.
We sought to prospectively assess the diagnostic performance of a high-resolution positron emission tomography (PET) scanner using mild breast compression (positron emission mammography [PEM]). Data were collected on concomitant medical conditions to assess potential confounding factors. At four centers, 94 consecutive women with known breast cancer or suspicious breast lesions received 18F-fluorodeoxyglucose (FDG) intravenously, followed by PEM scans. Readers were provided clinical histories and x-ray mammograms (when available). After excluding inevaluable cases and two cases of lymphoma, PEM readings were correlated with histopathology for 92 lesions in 77 women: 77 index lesions (42 malignant), 3 ipsilateral lesions (3 malignant), and 12 contralateral lesions (3 malignant). Of 48 cancers, 16 (33%) were clinically evident; 11 (23%) were ductal carcinoma in situ (DCIS), and 37 (77%) were invasive (30 ductal, 4 lobular, and 3 mixed; median size 21 mm). PEM depicted 10 of 11 (91%) DCIS and 33 of 37 (89%) invasive cancers. PEM was positive in 1 of 2 T1a tumors, 4 of 6 T1b tumors, 7 of 7 T1c tumors, and 4 of 4 cases where tumor size was not available (e.g., no surgical follow-up). PEM sensitivity for detecting cancer was 90%, specificity 86%, positive predictive value (PPV) 88%, negative predictive value (NPV) 88%, accuracy 88%, and area under the receiver-operating characteristic curve (Az) 0.918. In three patients, cancer foci were identified only on PEM, significantly changing patient management. Excluding eight diabetic subjects and eight subjects whose lesions were characterized as clearly benign with conventional imaging, PEM sensitivity was 91%, specificity 93%, PPV 95%, NPV 88%, accuracy 92%, and Az 0.949 when interpreted with mammographic and clinical findings. FDG PEM has high diagnostic accuracy for breast lesions, including DCIS.
A feasibility study is presented for a small, low-cost, dedicated device for positron emission mammography. Two detector arrays above and below the breast would be placed in a conventional mammography unit. These detectors are sensitive to positron annihilation radiation, and are connected to a coincidence circuit and a multiplane image memory. Images of the distribution of positron-emitting isotope are obtained in real time by incrementing the memory location at the intersection of each line of response. Monte Carlo simulations of a breast phantom are compared with actual scans of this phantom in a conventional PET scanner. The simulations and experimental data are used to predict the performance of the proposed system. Spatial resolution experiments using very narrow bismuth germanate BGO crystals suggest that spatial resolutions of about 2 mm should be possible. The efficiency of the proposed device is about ten times that of a conventional brain scanner. The scatter fraction is greater, but the scattered radiation has a very flat distribution. By designing the device to fit in an existing mammography unit, conventional mammograms can be taken after the injection of the radio-pharmaceutical allowing exact registration of the emission and conventional mammographic images.
The use of biocidal copper oxide impregnated textiles in a long-term care ward may significantly reduce HAI, fever, antibiotic consumption, and related treatment costs.
We are developing a high specificity technique for detecting the increased metabolic rate of breast tiiinours. The glitcose analog FDG is known to concentrate in breast tiinlours rendering them easily detectable in conventional PET scans. Since PET is a relatively expensive imging technique it has not been used routinely in the detection of breast cancer. Positron emission mtnrnography (PEM) will provide a highly eficient, high sputial resolution, and low cost positron irtulging system whose rnetabolic irnages are co-registered with conventional mnmtnography. Coincidences betweeti hoo BGO blocks CUI into 2 x 2 tnrn squares coitpled to two 7.5 crn square inuiging PMTs are detected and back-projected to form reultirne multiple plane irnages. The design is about 20 tinles more sensitive than a conventional multi-slice PET body scanner, so much less radio-pharmaceiitical can be wed, reducing the patient dose and cost per scan. Protoepe detectors hose been t n d e and extensive rneasurernents done. The device is expected to have an in-plane spatial resolution about 2 intn FWHM. Besides the application as N secondup screening tool the device may be beneficial in rrzeasiiring a tiirrwur's response to ruriio-therapy or cherno-therapy as well as uiding the surgeon in optimizing the removal of inalignant tissue.
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