Overexpression of folate receptors (FRs) on different tumor types (e.g., ovarian, lung) make FRs attractive in vivo targets for directed diagnostic/therapeutic agents. Currently, no diagnostic agent suitable for positron emission tomography (PET) has been adopted for clinical FR imaging. In this work, two 55Co-labeled albumin-binding folate derivatives-[55Co]Co-cm10 and [55Co]Co-rf42-with characteristics suitable for PET imaging have been developed and evaluated. High radiochemical yields (≥95%) and in vitro stabilities (≥93%) were achieved for both compounds, and cell assays demonstrated FR-mediated uptake. Both 55Co-labeled folate conjugates demonstrated high tumor uptake of 17% injected activity per gram of tissue (IA/g) at 4 h in biodistribution studies performed in KB tumor-bearing mice. Renal uptake was similar to other albumin-binding folate derivatives, and liver uptake was lower than that of previously reported [64Cu]Cu-rf42. Small animal PET/CT images confirmed the biodistribution results and showed the clear delineation of FR-expressing tumors.
19 April 2022 in Journal of Biomechanical Engineering
Wall shear stress (WSS) is an important mediator of cardiovascular pathologies and there is a need for its reliable evaluation as a potential prognostic indicator. The purpose of this work was to develop a method that quantifies WSS from two-dimensional (2D) phase contrast magnetic resonance (PCMR) imaging derived flow waveforms, apply this method to PCMR data acquired in the abdominal aorta of healthy volunteers, and to compare PCMR-derived WSS values to values predicted from a computational fluid dynamics (CFD) simulation. The method uses PCMR-derived flow versus time waveforms constrained by the Womersley solution for pulsatile flow in a cylindrical tube. The method was evaluated for sensitivity to input parameters, intrastudy repeatability and was compared with results from a patient-specific CFD simulation. 2D-PCMR data were acquired in the aortas of healthy men (n = 12) and women (n = 15) and time-averaged WSS (TAWSS) was compared. Agreement was observed when comparing TAWSS between CFD and the PCMR flow-based method with a correlation coefficient of 0.88 (CFD: 15.0 ± 1.9 versus MRI: 13.5 ± 2.4 dyn/cm2) though comparison of WSS values between the PCMR-based method and CFD predictions indicate that the PCMR method underestimated instantaneous WSS by 3.7 ± 7.6 dyn/cm2. We found no significant difference in TAWSS magnitude between the sexes; 8.19 ± 2.25 versus 8.07 ± 1.71 dyn/cm2, p = 0.16 for men and women, respectively.