It takes two: “transport cocktails” for solid tumor alpha-particle radiotherapy and their digital twins
Speaker
Yannis Kevrekidis
Bloomberg Distinguished Professor, Chemical and Biomolecular Engineering, Applied Mathematics and Statistics & the Medical School at John Hopkins University
Stavroula Sofou
Professor and Director of Graduate Studies in the Department of Chemical
and Biomolecular Engineering at Johns Hopkins University
Abstract
It takes two: “transport cocktails” for solid tumor alpha-particle radiotherapy and their digital twins
Heterogeneous intratumoral alpha-particle microdistributions, which are especially pronounced in established (i.e. large, vascularized) solid tumors, are a major reason for treatment failure, since cancer cells not being hit by alpha-particles will likely not be killed. We interrogated a novel therapeutic strategy of simultaneously employing more than one, separate delivery carriers of the same alpha-particle emitter, Actinium-225. The carriers were chosen to deliver their therapeutic cargo in complementary regions of the same solid tumor. Collectively, the alpha-particle emitters became well-spread within established, soft-tissue solid tumors. This strategy resulted in remarkable improvements in cancer therapy, namely, better tumor growth inhibition and prolonged survival, in tumor bearing mice at low administered activities. This was shown to be a tumor agnostic strategy by demonstrating its applicability on solid tumors of different origin. The physics, transport considerations, dosimetry and therapeutic effects are investigated and presented at the single-cell scale, the scale of multicellular spheroids and/or the whole-body animal scale. Additionally, a digital twin was built using first principles reaction-transport models (quantitatively informed by experiments) that reproduces and rationalizes the "geographically complementary" behaviours of such “carrier cocktails.” This mathematical model opens the way to the optimal design of carrier cocktails along with their delivery protocols.
Bio
Stavroula Sofou is a Professor and Director of Graduate studies in the department of Chemical and Biomolecular Engineering at Johns Hopkins University (JHU). She is a member of the Cancer Invasion and Metastasis Program at the JHU Sidney Kimmel Comprehensive Cancer Center, has a secondary appointment in the Department of Oncology, and is an associate member at the Institute of NanoBioTechnology. Sofou is most known for her non-traditional approaches to combat difficult-to-kill cancers in diffusion-limited environments. Her research interests range from fundamental studies of lipid bilayers to applications of biomaterials for drug delivery (alpha-particle emitters, chemotherapeutics, gene therapy). Sofou earned her PhD in Chemical Engineering at Columbia University, held a post-doctoral fellowship in Medical Physics/Experimental Therapeutics at Memorial Sloan-Kettering Cancer Center, was an assistant professor at NYU-Poly (now Tandon School of Engineering) and associate professor at Rutgers University. The first publication on the two-carrier approach was the featured basic science article in JNM, and was awarded the 2023 top cancer research paper by the Academy of Athens, Greece.
Yannis Kevrekidis studied Chemical Engineering at the National Technical University in Athens. He then followed the steps of many alumni of that department to the University of Minnesota, where he studied with Rutherford Aris and Lanny Schmidt (as well as Don Aronson and Dick McGehee in Math). He was a Director's Fellow at the Center for Nonlinear Studies in Los Alamos in 1985-86 (when Soviets still existed and research funds were plentiful). He then had the good fortune of joining the faculty at Princeton, where he taught Chemical Engineering and also Applied and Computational Mathematics for 31 years; seven years ago he became Emeritus and started fresh at Johns Hopkins (where he somehow is also Professor of Urology). His work always had to do with nonlinear dynamics (from instabilities and bifurcation algorithms to spatiotemporal patterns to data science in the 90s, nonlinear identification, multiscale modeling, and back to data science/ML); and he had the additional good fortune to work with several truly talented experimentalists, like G. Ertl's group in Berlin. Currently -on leave from Hopkins- he works with the Defense Sciences Office at DARPA. When young and promising he was a Packard Fellow, a Presidential Young Investigator and the Ulam Scholar at Los Alamos National Laboratory. He holds the Colburn, CAST Wilhelm and Walker awards of the AIChE, the Crawford and the Reid prizes of SIAM, he is a member of the NAE, the American Academy of Arts and Sciences, and the Academy of Athens.