Theoretic Criteria for Antibody Penetration into Solid Tumors and Micrometastases

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 tu-mor 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 pene-tration rate. Results: Even low rates of antigen internalization from constitutive membrane turnover can significantly retard an-tibody penetration. Rapid clearance of single-chain variable frag-ments 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 micro-metastases than vascularized tumors. Key Words: molecular imaging; monoclonal antibodies; radio-nuclide therapy; biodistribution; penetration; pharmacokinetic