Imaging for Y90 Microscphere SIRT Planning Grant

abstract

  • Yttrium-90 (Y-90) microsphere radioembolization, known as Selective Internal Radiation Therapy (SIRT), via hepatic arterial administration is a treatment for patients with primary and metastatic liver cancer because the primary blood supply to liver tumors is from the hepatic artery while the majority of the blood supply to the normal liver is from the portal vein. The micro-vascular density of liver tumors is 3-200 times greater than the surrounding liver parenchyma further improving the selectivity of the therapy to the tumor. In this treatment, 30 5m diameter spheres labeled with the radioactive isotope Y-90 (a high-energy beta particle-emitting radioisotope) become lodged in the arterioles within the tumor and destroy the tumor while leaving the normal liver tissue mostly unharmed. For treatment planning Tc-99m-macro aggregated albumin (MAA) is infused into the proper hepatic artery and a perfusion scintigraphy is performed. However, the significant difference in size, shape, and other properties of the MAA and the Y-90 microspheres complicates the treatment planning because the MAA particles cannot be expected to distribute the same as the Y-90 microspheres. Thus it is desirable to develop and use a new biodegradable sphere for accurate SIRT planning. Nano and microparticles of biodegradable materials like Poly(lactic-co-glycolic acid) (PLGA), Polyanhydrides, and Chitosan, have been investigated widely for drug delivery. They have been shown to be both biocompatible and biodegradable. More recently, a new synthetic biodegradable elastomer Poly(glycerol Dodecanedioate) (PGD) has been developed for medical devices and tissue engineering scaffolds. These polymers will be used, employing different emulsion techniques, to produce approximately 30 5m size biodegradable microspheres to match the size and shape of the Y-90 microspheres used in the treatment. Once obtained, the different particles will be submitted to in vitro degradation studies in phosphate buffer and characterized with respect to shape, size, size distribution, surface roughness, and porosity using scanning electron microscope. Yttrium-90 (Y-90) microsphere radioembolization, known as Selective Internal Radiation Therapy (SIRT), via hepatic arterial administration is a treatment for patients with primary and metastatic liver cancer because the primary blood supply to liver tumors is from the hepatic artery while the majority of the blood supply to the normal liver is from the portal vein. The use of a specific chelator (coupling chemical) attached to the surface of the particles will also be evaluated for labeling yields, radiochemical purity and stability of the final product. The final step of the project is the in vivo evaluation of the particles; which will be evaluated in Sprague Dawley rats. The animals will be euthanized at different times and the samples of blood, lung, liver, kidney, and spleen will be collected for measuring of radioactive content in a gamma well counter. Numerical dosimetry calculations will be done to evaluate the radiation field and dose distributions and assure radioprotection standards are met. PUBLIC HEALTH RELEVANCE: Colorectal cancer is one of the most common malignancies in industrialized nations, ranking fourth behind lung, breast and prostate cancers. About 140,000 new cases are diagnosed annually in the United States according to the American Cancer Society. A new biodegradable spherical radio-microsphere used for Selective Internal Radiation Therapy (SIRT) planning will decrease the risk of lung and stomach damage, bone marrow suppression, liver and other organs failure that could result from Y-90 SIRT and thus improve the therapeutic effects of the SIRT in patients.

date/time interval

  • June 1, 2011 - May 31, 2014

sponsor award ID

  • 1R21CA159073-01A1

local award ID

  • AWD000000001540

contributor

keywords

  • 90Y
  • Albumins
  • American Cancer Society
  • Anatomy
  • Angiography
  • Animals
  • Beta Particle
  • Bile duct carcinoma
  • Biocompatible
  • Biodegradable microsphere
  • Biodegradation
  • Biodistribution
  • Blood Vessels
  • Blood specimen
  • Bone Marrow Suppression
  • Caliber
  • Chelating Agents
  • Chemicals
  • Chemistry
  • Chitosan
  • Clinical
  • Code
  • Colorectal
  • Colorectal Cancer
  • Computer software
  • Coupling
  • Deposition
  • Detection
  • Developed Countries
  • Diagnosis
  • Discipline of Nuclear Medicine
  • Dose
  • Drug Delivery Systems
  • Drug Formulations
  • Elastomers
  • Electron Microscope
  • Emulsions
  • Evaluation
  • Future
  • Glycerol
  • Glycolates
  • Goals
  • Hepatic
  • Hepatic artery
  • Hour
  • Image
  • Imaging technology
  • In Vitro
  • Kidney
  • Knowledge
  • Label
  • Left
  • Liver
  • Liver diseases
  • Liver neoplasms
  • Liver parenchyma
  • Lung
  • Malignant Neoplasms
  • Malignant neoplasm of liver
  • Malignant neoplasm of lung
  • Malignant neoplasm of prostate
  • Measurement
  • Measures
  • Medical Device
  • Methods
  • Microspheres
  • Modeling
  • Monitor
  • Neoplasm Metastasis
  • Neuroendocrine Tumors
  • Organ failure
  • Oryctolagus cuniculus
  • Outcome
  • Pancreas
  • Patients
  • Perfusion
  • Phosphate Buffer
  • Polyanhydrides
  • Polymers
  • Porosity
  • Portal vein structure
  • Primary Neoplasm
  • Property
  • Publishing
  • Radiation
  • Radiation therapy
  • Radio
  • Radioactive
  • Radioisotopes
  • Radiolabeled
  • Radionuclide Imaging
  • Radioprotection
  • Rattus
  • Research
  • Risk
  • Scanning
  • Shapes
  • Shunt Device
  • Site
  • Spleen
  • Sprague-Dawley Rats
  • Stomach
  • Surface
  • Survival Rate
  • Technetium 99m
  • Techniques
  • Testing
  • Therapeutic
  • Therapeutic Effect
  • Therapeutic Intervention
  • Time
  • Tissue Engineering
  • Tissues
  • United States
  • Unresectable
  • Vascular blood supply
  • Visceral
  • Work
  • arteriole
  • base
  • biocompatible polymer
  • biodegradable polymer
  • density
  • design
  • dosimetry
  • gastrointestinal
  • improved
  • in vivo
  • internal radiation
  • liver imaging
  • malignant breast neoplasm
  • meetings
  • metastatic colorectal
  • nano
  • outcome forecast
  • particle
  • radiochemical
  • radiotracer
  • response
  • scaffold
  • treatment planning
  • tumor
  • uptake