Theoretic Criteria for Antibody Penetration into Solid Tumors and Micrometastases

Journal of Nuclear Medicine

Greg M. Thurber¹  Stefan C. Zajic¹  K. Dane Wittrup¹ 

关键词: molecular imaging;    monoclonal antibodies;    radionuclide therapy;    biodistribution;    penetration;    pharmacokinetics;   

DOI  :  10.2967/jnumed.106.037069

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Targeting tumors with antibody-based therapeutics is a complex task presenting multiple kinetic barriers. Antibody internalization and clearance inhibit uptake both in solid tumors, limited by tumor vascular permeability, and in micrometastases, limited by diffusion. Methods: A modeling exercise is used to introduce 2 simple criteria that must be less than unity for saturation of both tumors and micrometastases. The clearance modulus and the Thiele modulus are ratios of the plasma clearance rate and antibody catabolism, respectively, to the tumor tissue penetration rate. Results: Even low rates of antigen internalization from constitutive membrane turnover can significantly retard antibody penetration. Rapid clearance of single-chain variable fragments also hinders uptake, often more than counterbalancing their more rapid extravasation and diffusion. Conclusion: The model illustrates that with the large resistance from the tumor capillary, antibodies may be more suitable for targeting micrometastases than vascularized tumors.

【 授权许可】

Unknown