William E. McLaughlin

Multimodality Animal Rotation Imaging System (MARS) for In Vivo Detection of Intraperitoneal Tumors

Citation Pizzonia J, Holmberg J, Orton S, Alvero A, Viteri O, Mclaughlin W, Feke G, Mor G. Multimodality animal rotation imaging system (MARS) for in vivo detection of intraperitoneal tumors. Am J Reprod Immunol 2012; 67: 84–90

Increased sensitivity in antigen detection with fluorescent latex nanosphere-IgG antibody conjugates.

IgG antibodies were conjugated to Kodak X-Sight nanospheres to develop fluorescent-labeled antibodies using two different synthetic routes: one involving the DTT reduction method, and the other involving Trauts Reagent modification method. These two methods result in different conjugation efficiencies and different performances in antigen detection. Western blotting shows that the nanosphere-IgG antibody conjugates synthesized using the DTT reduction method are more immunospecific than the conjugates synthesized using Trauts Reagent modification method. In addition, the conjugates synthesized using DTT reduction also show higher antigen detection sensitivity than other commercially available fluorescent-IgG antibody conjugates, including Alexa Fluor, Qdot, and CyDye conjugates.

Abstract 4288: in vivo Imaging of early inflammation response in bacterial infection

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Staphylococcus aureus (S. aureus) causes significant morbidity and mortality worldwide and a prime cause in hospital infections. Staphylococcus aureus bactereremia is prevalent in neutropenic cancer patients, and malignancies form a sizeable risk factor for methycillin-resistant S. aureus (MRSA) infections. Targeting the virulence products is a promising approach for developing novel therapeutics. A detailed understanding of the virulence factors and the resultant immune response is quite essential for such development. Here, we established an athymic mice model to assess the initial immune response to S.aureus inoculation. As the polymorphonuclear neutrophils(PMN)and macrophages are a part of the early response, determination of its myeloperoxidase (MPO) activity in vivo is established. MPO is an inflammatory heme protein and utilizes hydrogen peroxide in the process of reactive oxygen species generation. 24 hrs after the intra muscular injection of the S.aureus bacterial lysate, the MPO activity was detected by i.p injection of luminal in mice. The blue luminescence resulting from the MPO activity was imaged and the luminescence images were overlaid on planar X-ray images for anatomical co-registration. The results show a robust MPO activity in the mouse bladder. This increase in MPO activity as a result of neutrophil activation at the bladder region was further confirmed using non-invasive X-ray contrast imaging of the bladder and co-registering the luminescence and the X-ray density signals at the bladder. The initial response shown here has similarities with the mechanism suggested recently for myobacterium bovis bacillus Calmette-Guerin (BCG) treatment of bladder cancer. Bacterial components, its structures that are involved in eliciting the robust PMN infiltration in bladder will be very valuable in the developing better bladder cancer anti-tumor treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4288. doi:1538-7445.AM2012-4288

Abstract 5329: Degradable multimodal nanoparticles with fluorescence and magnetic resonance contrast

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Molecular Imaging is making rapid strides as a tool in understanding and the cure of cancer. Like no panacea, here again a need of multimodality exists, where more than one modality is becoming a necessity to cogently decipher the role or action of the biomolecule in the pathology or cure. Here, we developed a multimodal nanoparticle (NP) that can be simultaneously be imaged by optical, and magnetic resonance Imaging (MRI) modalities. In combination, the two modalities compensate each others deficiencies in the spatial resolution, sensitivity, and the depth detection. Encapsulation of MR contrast and amine functionalization was performed in a one pot synthesis by microemulsion technique with supra magnetic iron oxide (SPIO). The hydrodynamic radii of nanoparticle and zeta potential were measured using Nicomp 380 zls particle sizer. 9L gliosarcoma tumor bearing rat model was administered with the SPIO nanoparticles and validated using 7 tesla MRI scanner. PEGylated SPIO nanoparticles after conjugation with water soluble, near-infrared (NIR) tricarbocyanine, cyclic enamine-functionalized dye, were injected intratumorally and monitored noninvasively using near-IR fluorescence imager. Steady retention in the tumor as compared to the free near-infrared (NIR) dye injected into the control mice indicates the dye-colloidal particle dwell characteristics and suitability for targeted diagnostics. In summary, we have described the development of a simple and efficient dynamic Imaging multimodal nanoparticle to be used for NIRF and MR Imaging. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5329. doi:10.1158/1538-7445.AM2011-5329

Abstract 2649: Whole body vibration effects on binding kinetics and targeting of near-infrared dye conjugated bisphosphonate

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC A non-invasive means of targeting bisphophonate to specific skeletal sites, along with the passive binding/decay kinetics of the near-infrared bisphosphanate analog to the skeleton are determined. Bone is the third common site where breast, lung, and prostate cancer cells spread and metastasize. Debilitating pain is the major complication resulting from bone metastases in nearly 70% of the patients. The palliative bone pain management includes the bisphosphanate therapy. Bisphosphonates, a potent inhibitor of bone resorption, gives both pain relief and improves bone health. However these medications result in complications such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). Combinations of low-risk exercise programs along with reduced drug dosage are a likely alternative to counter such drug-related side effects. Site-selective skeletal targeting of bisphosphonates, if feasible, is however ideal to overcome drug-related side effects. We utilized whole body vibration (WBV), to target NIR dye conjugate bisphosphonate to specific skeletal sites. Using near-infrared (NIR) fluorescence imaging, both the targeting and the passive binding of the bisphosphonate in vivo was determined. Vibration loading, utilizing whole body vibration (WBV) was performed on twelve mice by subjecting them to vibration frequency of 35 Hz for fifteen min (5-10 times/week) duration. Alendronate was conjugated to near-infrared tricarbocyanine, cyclic enamine-functionalized dye, and was injected intravenously after 21-day exercise regime. Yet to be reported, we show that NIR-alendronate probe bound to the lumbar L6 vertebrae, resultant of direct high-frequency WBV stimulation. This is besides several other specific targeting sites. Further, both the passive binding and the decay kinetics of the NIR signal at the skeleton was determined in a six-week non-invasive longitudinal study of mouse pups. This provides opportunity to utilize such approaches in future translational studies in assessing the role of bisphosphonates in preventing spreading of cancer cells at other secondary sites, especially bone. The targeted drug binding in response to the vibratory protocol also provides hope in the development of whole body vibration (WBV) as a bisphosphonate-therapeutic aid. Further, to develop strategies in reducing the drug dosage in treatment of other morbidity factors that stem from complications from bone metastases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2649.