Event
Bioengineering Seminar Series: Mikhail Papisov
Friday, May 4, 2012
11:00 a.m.-12:00 p.m.
Room 1200 Jeong H. Kim Engineering Bldg.
Professor Silvia Muro
muro@umd.edu
Development of Clinically Feasible Nanoconstructs: the Role of Quantitative PET Imaging
Mikhail Papisov
Assistant Professor of Radiology
Massachusetts General Hospital
With the growing number of biopharmaceuticals and drug-carrying nanoconstructs entering preclinical and clinical studies (over 60% of the industry pipeline), quantitative imaging of their pharmacokinetics (PK) is playing an increasingly important role. PET is a fully quantitative imaging modality most suitable for PK research in vivo, in small and large animals.
The intrinsically slow in vivo transfer of many large molecules requires labeling of the drug candidate with radionuclides that have long physical half-lives. Among all currently available positron emitters suitable for PET, 124I has the longest physical half-life (4.2 d) but is a known as non-pure positron emitter. The objective of our studies was to determine whether PET with 124I enables image and data quality suitable for PK studies.
Imaging was performed using MicroPET P4 and MicroPET Focus 220 (Siemens/Concorde Microsystems), the latter in combination with CT imaging. Spatial resolution and linearity of the positron count-rate were measured in vitro. In vivo, imaging studies were carried out in mice, rats and non-human primates. Five recombinant human enzymes, soluble polymers, virions and synthetic and phage particles were labeled with 124I their pharmacokinetics were investigated by quantitative imaging on different time frames, from minutes to two weeks.
The results suggest that PET, in particular with 124I, is an exceptional method for quantitative investigation of slow as well as fast stages of the PK of biopharmaceuticals. PET is especially advantageous for studies in large and rare animals. PET also provides excellent information for both visual and quantitative analysis of systems with complex pharmacokinetics, such as biomolecule delivery to CNS via intrathecal (leptomeningeal) route. PET studies in nonhuman primates facilitate mechanistic analysis and data scaling, and thus provide valuable guidance for the planning of clinical trials.
