Imaging spontaneous MMTVneu transgenic murine mammary tumors: targeting metabolic activity versus genetic products.

INTRODUCTION: Despite the great strides made in imaging breast cancer (BC) in humans, the current imaging modalities miss up to 30% of BC, do not distinguish malignant lesions from benign ones, and require histologic examinations for which invasive biopsy must be performed. Annually in the United States, approximately 5.6 million biopsies find benign lesions. More than 50% of human BCs overexpress cyclin D1, and all BCs exhibit VPAC1 oncogene products. Together, these gene products may provide an excellent biomarker for the early and accurate detection of BC. We have evaluated 4 biologically active peptide analogs that have high affinity for VPAC1. The transgenic MMTVneu mice spontaneously develop BC and metastatic lesions that overexpress cyclin D1 and VPAC1 biomarkers. The MMTVneu mouse, therefore, provides an excellent animal model that mimics the pathogenesis of human BC. The objective of this investigation was to determine the ability of 1 of the peptide analogs, (64)Cu-TP3805, to detect BC in MMTVneu mice using (18)F-FDG as a gold standard. METHODS: The transgenic MMTVneu mouse colony was maintained. Offspring were screened for transgenic status by reverse transcriptase polymerase chain reaction (RT-PCR). Nine mice with visible, palpable, or unknown metastatic lesions were entered into the protocol. (18)F-FDG (6,475 +/- 1,628 kBq [175 +/- 44 microCi]) PET served as a control, followed by a CT scan and 24-48 h later by PET with (64)Cu-TP3805 (4,588 +/- 962 kBq [124 +/- 26 microCi]). RT-PCR on excised tumors determined VPAC1 expression, and histology ascertained the pathology. RESULTS: Ten tumors were detected by PET. Four tumors were detected both by (18)F-FDG and by (64)Cu-TP3805. Additionally, 4 tumors were imaged with (64)Cu-TP3805 only. These 8 tumors overexpressed VPAC1 receptors and were malignant by histology. The 2 remaining tumors were visualized with (18)F-FDG only. These tumors did not express the VPAC1 oncogene product and had benign histology. The standard uptake value ranged from 3.1 to 18.3 for (64)Cu-TP3805 and 0.9 to 1.4 for (18)F-FDG. CONCLUSION: (64)Cu-TP3805 identified all malignant lesions unequivocally that overexpressed the VPAC1 oncogene surface product. The 2 benign tumors that did not express the VPAC1 receptor were not imaged. (64)Cu-TP3805 promises to have the potential for the early and accurate imaging of primary and metastatic BC

Targeting apoptosis for optical imaging of infection

PURPOSE: Infection is ubiquitous and a major cause of morbidity and mortality. The most reliable method for localizing infection requires radiolabeling autologous white blood cells ex vivo. A compound that can be injected directly into a patient and can selectively image infectious foci will eliminate the drawbacks. The resolution of infection is associated with neutrophil apoptosis and necrosis presenting phosphatidylserine (PS) on the neutrophil outer leaflet. Targeting PS with intravenous administration of a PS-specific, near-infrared (NIR) fluorophore will permit localization of infectious foci by optical imaging. METHODS: Bacterial infection and sterile inflammation were induced in separate groups (n = 5) of mice. PS was targeted with a NIR fluorophore, PSVue(®)794 (2.7 pmol). Imaging was performed (ex = 730 nm, em = 830 nm) using Kodak Multispectral FX-Pro system. The contralateral normal thigh served as an individualized control. Confocal microscopy of normal and apoptotic neutrophils and bacteria confirmed PS specificity. RESULTS: Lesions, with a 10-s image acquisition, were unequivocally visible at 5 min post-injection. At 3 h post-injection, the lesion to background intensity ratios in the foci of infection (6.6 ± 0.2) were greater than those in inflammation (3.2 ± 0.5). Image fusions confirmed anatomical locations of the lesions. Confocal microscopy determined the fluorophore specificity for PS. CONCLUSIONS: Targeting PS presented on the outer leaflet of apoptotic or necrotic neutrophils as well as gram-positive microorganism with PS-specific NIR fluorophore provides a sensitive means of imaging infection. Literature indicates that NIR fluorophores can be detected 7-14 cm deep in tissue. This observation together with the excellent results and the continued development of versatile imaging devices could make optical imaging a simple, specific, and rapid modality for imaging infection

Three Dimensional Projection Environment for Molecular Design and Surgical Simulation

Poster presented at Medicine Meets Virtual Reality conference February 8-12, 2011 in Newport Beach, California. Conclusions: Turning 2D CT/PET slices into 3D objects assists in understanding the topology surrounding tumor masses. Incorporating the visual and physical characteristics of a patient’s anatomy will provide surgeons with an informative pre-operative tool to plan and practice the operation before the first incision. Including haptic feedback provides a familiar \u27feel\u27 to surgeons as they palpate the target organ, trying to locate the tumor and determine how large a margin of resection will be needed. The development of genetic PET imaging and contrast CT into a combined visual will further improve the surgeons’ knowledge by more accurately pinpointing malignant tissue and any hidden blood vessels