title: Review: update on selection of optimal radiopharmaceuticals for clinical trials.
abstract: Multiple formulations of radiopharmaceuticals (RPs) are possible because of engineering at the nanometer scale. Yet, numbers of patients are limited, and the cost of each clinical trial is high. Thus, there is the need of preclinical evaluation of one agent versus another for the selection of an optimal choice. In the application of RPs to cancer, this selection involves both visualization and treatment aspects. In this paper, we propose the use of imaging and therapeutic figures of merit (IFOM and TFOM, respectively) to select the optimal structure and radiolabel for subsequent clinical trials given animal biodistribution results. Limiting cases and Monte Carlo simulation were used to demonstrate that these modern figures of merit are superior to traditional ratio functions that have been employed in these two contexts. Finally, there is the question of how animal and human results resemble each other kinetically. We considered allometry and compared mouse and human results for several of the cognate cT84.66 antibodies (anti-CEA; carcinoembryonic antigen). While kinetics of intact and 120-kDa engineered proteins are similar across the two species, the 80-kDa cognate shows a manifest difference in the RP first moment in the blood. In particular, human blood clearance is slower than that seen in the nude mouse. We suggest that such allometric comparisons become standard in the reporting of clinical trials.
authors.affiliation: City of Hope, Duarte, CA 91010, USA. lwilliams@coh.org <lwilliams@coh.org>
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Williams
authors.forename: George
authors.initials: G
authors.lastname: Lopatin
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Kaplan
authors.forename: An
authors.initials: A
authors.lastname: Liu
authors.forename: Jeffrey Y C
authors.initials: JY
authors.lastname: Wong
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000627:therapeutic use*
chemical_list: D019275:Radiopharmaceuticals