InvivoPharm is a preclinical contract research organisation (CRO) providing services in the general areas of drug-
receptor occupancy, radiolabeled drug distribution and autoradiography.
Quantitative Whole-Body Autoradiography Service
Whole-body autoradiography produces an image of the distribution of a radiolabeled test drug over the entire animal.
Radioactivity is imaged and quantified using phosphor imaging. Whole-body autoradiography is useful for
determination of the following drug distribution parameters:
• Biodistribution and pharmacokinetics in both target and non-target organs
• Sites of accumulation or retention of the drug, including small organs and individual tissues
• Ability to cross blood-brain and placental barriers or penetrate tumors
• Guiding toxicology studies
• Potential of radiopharmaceuticals for PET / SPECT imaging and organ dosimetry
• Routes of elimination
In Vitro Autoradiography Service
In vitro autoradiography images the distribution of radioactivity in the brain or other target organ following incubation of
cryostat-cut tissue sections in a radioactive drug. It can be used for determining the distribution and density of drug
receptors in the tissue sections. It can also be used for competition-type assays where IC50 for a non-radioactive test
drug to displace the receptor-binding of a standard radiotracer to various regions-of-interest in the sections is
determined.
In Vivo Receptor Occupancy
Measures the degree to which the test drug actually occupies its receptor in vivo. Receptor occupancy is determined
by measuring the ability of a systemic dose of the test drug (non-radioactive) to compete with in vivo binding of a
radiolabeled drug to the receptor. Useful to determine the dose or plasma concentration of the test drug needed to
reach a therapeutically effective occupancy level.
Examples of therapeutically effective receptor occupancy ranges for drugs:
receptor occupancy, radiolabeled drug distribution and autoradiography.
Quantitative Whole-Body Autoradiography Service
Whole-body autoradiography produces an image of the distribution of a radiolabeled test drug over the entire animal.
Radioactivity is imaged and quantified using phosphor imaging. Whole-body autoradiography is useful for
determination of the following drug distribution parameters:
• Biodistribution and pharmacokinetics in both target and non-target organs
• Sites of accumulation or retention of the drug, including small organs and individual tissues
• Ability to cross blood-brain and placental barriers or penetrate tumors
• Guiding toxicology studies
• Potential of radiopharmaceuticals for PET / SPECT imaging and organ dosimetry
• Routes of elimination
In Vitro Autoradiography Service
In vitro autoradiography images the distribution of radioactivity in the brain or other target organ following incubation of
cryostat-cut tissue sections in a radioactive drug. It can be used for determining the distribution and density of drug
receptors in the tissue sections. It can also be used for competition-type assays where IC50 for a non-radioactive test
drug to displace the receptor-binding of a standard radiotracer to various regions-of-interest in the sections is
determined.
In Vivo Receptor Occupancy
Measures the degree to which the test drug actually occupies its receptor in vivo. Receptor occupancy is determined
by measuring the ability of a systemic dose of the test drug (non-radioactive) to compete with in vivo binding of a
radiolabeled drug to the receptor. Useful to determine the dose or plasma concentration of the test drug needed to
reach a therapeutically effective occupancy level.
Examples of therapeutically effective receptor occupancy ranges for drugs:
| Drug class |
Receptor |
Occupancy level (brain) |
Refs |
| Typical antipsychotics Atypical antipschotics Antidepressants Methylphenidate (ADHD) Rinonabant (appetite suppression) |
D2 receptor D2 receptor 5-HT uptake transporter DA uptake transporter CB1 receptor |
>65 % >45 % >80 % >50 % >65 % |
[1][2] [1][2] [3][4] [5] [6] |
References: [1] Waarde A., Curr Pharm Des 6 (2000) 1593-610; [2] Lee CM and Farde L., Trends Pharmacol Sci 27 (2006) 310-6; [3]
Meyer JH et al., Am J Psychiatry 158 (2001) 1843-9; [4] Meyer JH et al., Am J Psychiatry 161 (2004) 826-35; [5] Volkow ND et al., Am
J Psychiatry 155 (1998) 1325-31; [6] Need AB et al., Psychopharmacology 184 (2006) 26-35.
In Vitro Receptor Occupancy: Radioligand Binding Assay
Radioligand (competitive) binding assays determine the IC50 and Ki value for receptor-drug interactions in a tissue
homogenate by measuring the ability of the (non-radioactive) test drug to compete with binding of a radiolabeled drug
to the receptor.
Meyer JH et al., Am J Psychiatry 158 (2001) 1843-9; [4] Meyer JH et al., Am J Psychiatry 161 (2004) 826-35; [5] Volkow ND et al., Am
J Psychiatry 155 (1998) 1325-31; [6] Need AB et al., Psychopharmacology 184 (2006) 26-35.
In Vitro Receptor Occupancy: Radioligand Binding Assay
Radioligand (competitive) binding assays determine the IC50 and Ki value for receptor-drug interactions in a tissue
homogenate by measuring the ability of the (non-radioactive) test drug to compete with binding of a radiolabeled drug
to the receptor.
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Preclinical contract research services
InvivoPharm: Preclinical contract research CRO
© 2007, 2008 Invivopharm Inc.