Study Purpose
This study aims to determine the tissue distribution of radiolabeled test articles derived radioactivity using the quantitative whole-body autoradiography (QWBA) method. Based on the exposure and half-life in rodent tissues, the distribution results can provide the estimated effective dose of radioactivity to human subjects.
Platform Introduction
The radioactivity experimental platform of DMPK can provide a variety of species (CD-1 mouse, C57 mouse, SD rat, LE rat, NHP, small dog, etc.) models for QWBA study.
One animal/gender will be euthanized at a specific time point post dosing. All animals will be euthanized, and the carcasses will be immediately frozen. Quantitative whole-body autoradiography (QWBA) is applied to determine total radioactivity in various tissues (the table below) and in the area of interest (AOI).
Whole-body sections of the carcass in the CMC block will be performed in the large cryostat microtome and exposure to a 14C sensitive phosphor imaging plate. Selected tissues and AOI will be analyzed using quantitative whole-body autoradiography (QWBA) techniques and within AIDA software using a region sampling tool.
Tissue Group and Name
Vascular
Plasma (LSC)
Aorta
Blood (cardiac)
Endocrine
Adrenal gland
Adrenal cortex
Adrenal medulla
Pituitary gland
Thyroid gland
Muscular
Heart
Muscle (femoral)
Diaphragm
Skeletal
Bone (femur)
Bone marrow (femur)
Central Nervous System
Brain (whole)
Cerebellum
Brainstem
Spinal cord
Fatty
Brown fat
White fat (inguinal)
Reproductive
Epididymis
Prostate
Seminal vesicle
Testis
Secretory
Lachrymal gland
Ex-orbital lachrymal gland
Intra-orbital lachrymal gland
Harderian gland
Pancreas
Salivary gland
Ocular
Eye (whole)
Eye (ciliary body)
Eye (cornea)
Eye (iris)
Eye (sclera)
Eye (vitreous humor)
Lens
Uveal tract
Gastrointestinal (GI)
Oral mucosa
Tongue
Esophagus wall
Stomach wall (glandular)
Stomach wall (non-glandular)
Small intestine wall
Large intestine wall
Cecum mucosa
GI Tract Contents
Stomach contents
Small intestine contents
Large intestine contents
Cecum contents
Dermal
Skin; non-pigmented skin
Skin; pigmented skin
Metabolic/Excretory
Kidney
Kidney medulla
Kidney cortex
Bile (in duct)
Liver
Urinary bladder wall
Respiratory
Lung
Nasal turbinates
Trachea
Lymphatic
Lymph node (cervical)
Spleen
Thymus
Representative Quantitative Whole-body Autoradiography Images at Various Time Points following Oral Administration of [14C] Test Article to Male LE Rats
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