Professor
Undergraduate Program Director
Curriculum Vitae
Anthony.McGoron@fiu.edu
Office: EC 2677
Phone: (305) 348-1352
Fax: (305) 348-6954
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Drug Delivery, Molecular Imaging and Image guided Therapy
Molecular Imaging allows visualization of not only organs and cells, but also biochemical processes within the cells that are associated with a specific disease. This information can improve the accuracy of a diagnosis, provide better assessment of the severity of disease and even monitor the response to therapy. Molecular imaging approaches, such as nuclear (including PET and SPECT) and near-infrared fluorescence, have been applied to understand the molecular basis of diseases, biochemical processes, gene delivery and expression, tissue receptor-ligand activity, enzyme mediated processes, drug discovery, monitoring novel therapy techniques, etc. Our laboratory has been developing image guided therapy and dosimetry technologies for cancer and three-dimensional cell culture spheroid and organoid models to evaluate the therapies and more accurately predict the clinical response. We have developed micro and nanoparticles for image and therapy of cancer and image processing methods for improved dosimetry for therapy planning. We have developed PET radiochemicals that report regional metabolic/functional variables of various organs or tumors and examine their cellular uptake kinetics. In addition to clinical studies, tests are conducted in whole animal, isolated organ and isolated cell models. We are developing tools for automatic segmentation and registration of organs and tumors to accurately determine tumor functional and anatomical volumes, which is required for accurate dosimetry calculations for planning targeted radiotherapies.
A schematic of an ideal drug/imaging agent carrier for image guided therapy.
Radioactive Iodine Avidity of Differentiated Thyroid Cancer
Radioactive iodine (RAI) treatment is an established therapeutic tool for “differentiated thyroid cancers.” The therapeutic effectiveness is linked to the preservation of the iodine concentrating ability of the neoplastic tissue, a unique, inherent quality of a normal thyroid gland. Iodine concentration is a function involving expression of transport proteins and organification. Thyroid differentiation score (TDS) is an integrated quantity conveying the relative expression of proteins involved in histogenesis, morphologic and functional differentiation of thyroid tissue. The concept is well-described for expression of metabolic suppression of thyroid cancers associated with RAI-refractoriness. We evaluated the mRNA expressions of thyroid metabolomics-specific genes, comparing normal thyroid to neoplastic tissue in a cohort where patient-specific, paired data was available. Our analysis demonstrated that there was significant downregulation of the RAI theranostic transcriptome, much more significant in BRAF-initiated cancers vs RAS-initiated ones. There was also notable heterogeneity in respective mutational categories where individual assessment of thyroid differentiation profile (TDP) would potentially be clinically relevant for RAI treatment planning. Determination of TDP and development of a theranostic thyroid differentiation score (T-TDS) may have an impact on clinical decision making as to the extent of thyroidectomy and post-operative RAI therapy.
Heat map of the normalized log2(TPM+1) expression of each gene from normal tissue and from tumor tissue from each of 4 mutation status groups. The NIS gene (SLC5A5) is outlined in a white box.
Brain Organoid and Extracellular Vesicles
Cells communicate with each other and their surroundings to direct cellular development, movement, maintenance of homeostasis, immunological responses, and disease development. Much of the cell-cell communication occurs through nano-sized extravascular vesicles (EVs), which are released by all cells of the body. Since the EV content consists of biomolecules containing information related to the functional state of the cell generating them, they are of high interest in disease diagnosis. A better understanding of the role that EVs play in cell-cell communication will contribute to the development of diagnostics and therapeutics. Research to understand the role of EVs in cell-cell communication has generally used EVs generated from a 2-dimensional (2D) monolayer of cells to expose other cells and monitor the EV-mediated response of recipient cells. More recently, it was observed that cells grown as a 3-dimensional (3D) construct (spheroids), which more closely resemble the natural tissue shape, affects the number, and possibly the content, of EVs formed. It is predicted that EVs from organoids of multiple cell types and a more natural extracellular environment will recapitulate natural physiology even closer compared to spheroids and therefore the number and content of the EVs formed will be even more realistic.
68Ga-MAA Study
Selective internal radiation treatment (SIRT), a technique used to treat metastatic liver cancer, could also benefit from a PET perfusion tracer. During the planning stage, a 99mTc-MAA perfusion scan is performed to assess the allocation in lung and gastrointestinal tract. It is also used to calculate tumor to normal liver allocation ratio. The distribution acts as a predictor of the treatment safety and effectiveness. A PET perfusion agent (e.g., 68Ga-MAA) was developed that could provide valuable, quantifiable information to calculate precise doses, which could potentially improve the treatment outcome.
MAA microscope images; A: From original un-modified MAA kit and B: From re-lyophilized MAA on a hemocytometer slide.
Chitosan Microspheres for Imaging and Therapy
Fast biodegradable (12 h < half-life < 48 h) radioactive labeled microspheres are needed for PET and SPECT lung perfusion and radiomicrosphere therapy and therapy planning. We used an emulsion method to synthesize microspheres with biodegradable Chitosan glycol (CHSg). Microspheres were characterized and labeled with 99mTc or 68Ga as an alternative to MAA in perfusion PET and SPECT studies. The particles were also co-labeled with Y90 for therapy. Surface decoration of CHSg microspheres with p-SCN-Bn-NOTA was performed to increase 68Ga in vivo stability. 99mTc was labeled directly to the CHSg microspheres. p-SCN-Bn-DOTA was used for Y90 labeling. Labeling yield and in vitro radiochemical stability were evaluated.
Conjugation Chemistry of Ga-68 to Chitosan Microspheres
Chitosan microspheres
3D Liver Segmentation Method Using Computed Tomography for Selective Internal Radiation Therapy
Clinically, accurate liver volume determination for therapy planning is most often accomplished through tedious manual segmentation of the entire computerized tomography (CT) scan, a task greatly dependent on the skill of the operator. Automatic/semiautomatic approaches are thus geared towards segmenting and determining the volume of the liver accurately while facilitating the operational process from a clinician/physician’s viewpoint. We developed a novel liver segmentation approach for estimating anatomic liver volumes towards selective internal radiation treatment (SIRT). The algorithm requires minimal human interaction since the initialization process to segment the entire liver in 3D relied on a single computed tomography (CT) slice. The algorithm integrates a localized contouring algorithm with a modified k-means method. The modified k-means segments each slice into five distinct regions belonging to different structures. The liver region is further segmented using localized contouring. The novelty of the algorithm is in the design of the initialization masks for region contouring to minimize human intervention.
Modular block diagram of the main steps for liver segmentation and volume calculation.
3D-Model of liver tumors and supplying vasculature. Representation of the tumor and liver perfusion field. Selective treatment of individual lobes requires multimodal imaging (metabolism (FDG), perfusion (MAA) and anatomy (multiphase CT angiography).
FLT Study
Clinical evaluation and quantification of proliferative activity and tumor invasiveness can be performed using 3’-deoxy-3’-(18F)-fluorothymidine (18F-FLT) PET imaging. 18F-FLT works as a terminator of the growing DNA chain. Actually little 18F-FLT is accumulated in DNA, it is rather retained intracellularly after phosphorylation by thymidine kinase 1. This is analogous to the imaging of the glucose pathway with 18F-FDG after trapping by hexokinase. Both compounds therefore reflect accumulation by transport and subsequent activation by the first step in the utilization pathways. However, 18F-FLT does not reflect the whole of DNA synthesis just as 18F-FDG does not reflect the whole of glucose use.
We examined the imaging characteristics of pancreatic cancer patients to determine the correlation between the metabolic and proliferative activity of pancreatic cancer using FDG and FLT PET images, respectively. The parameters of interest were functional tumor volume (FTV), Total glycolytic index (TGI) and Total proliferative index (TPI). FTV, TGI and TPI were determined from both FDG and FLT PET images. These parameters measure the metabolic and proliferation activity of tumors using FDG and FLT PET/CT images, respectively, which have clinical value in the assessment of tumor biology, prognosis, response to treatment evaluation, and patient selection for therapeutic interventions.
3D rendered volume of pancreas (red) and tumor volume delineated based on the uptake of only FDG (yellow) (left), and FDG and FLT (pink) superimposed (right)
https://www.ncbi.nlm.nih.gov/sites/myncbi/anthony.mcgoron.1/bibliography/46421990/public/?sortby=pubDate&sdirection=descending