Patients with metastatic differentiated thyroid cancer (DTC) may be prepared using either thyroid-stimulating hormone withdrawal (THW) or recombinant human thyroid-stimulating hormone (rhTSH) injections before 131 I administration for treatment. The objective of this study was to compare the absorbed dose to the critical organs and tumors determined by 124 I PET/CT-based dosimetry for 131 I therapy of metastatic DTC when the same patient was prepared with and imaged after both THW and rhTSH injections. Methods: Four DTC patients at MedStar Washington Hospital Center were first prepared using the rhTSH method and imaged by 124 I PET/CT at 2, 24, 48, 72, and 96 h after administration of approximately 30-63 MBq of 124 I. After 5-8 wk, the same patients were prepared using the THW method and imaged as before. The 124 I PET/CT images acquired as part of a prospective study were used to perform retrospective dosimetric calculations for 131 I therapy for the normal organs with the dosimetry package 3D-RD. The absorbed doses from 131 I for the lungs, liver, heart, kidneys, and bone marrow were obtained for each study (rhTSH and THW). Twenty-two lesions in 3 patients were identified. The contours were drawn on each PET image of each study. Time-integrated activity coefficients were calculated and used as input in OLINDA/EXM sphere dose calculator to obtain the absorbed dose to tumors. Results: The THW-to-rhTSH organ absorbed dose ratio averaged over 5 organs for the first 3 patients was 1.5, 2.5, and 0.64, respectively, and averaged over 3 organs for the fourth patient was 1.1. The absorbed dose per unit administered activity to the bone marrow was 0.13, 0.086, 0.33, and 0.068 mGy/MBq after rhTSH and 0.11, 0.14, 0.22, and 0.080 mGy/MBq after THW for each patient, respectively. With the exception of 3 lesions of 1 patient, the absorbed dose per unit administered activity of 131 I was higher in the THW study than in the rhTSH study. The ratio of the average tumor absorbed dose after stimulation by THW compared with stimulation by rhTSH injections was 3.9, 27, and 1.4 for patient 1, patient 2, and patient 3, respectively. The ratio of mean tumor to bone marrow absorbed dose per unit administered activity of 131 I, after THW and rhTSH, was 232 and 62 (patient 1), 12 and 0.78 (patient 2), and 22 and 11 (patient 3), respectively. Conclusion: The results suggest a high patient variability in the overall absorbed dose to the normal organs per MBq of 131 I administered, between the 2 TSH stimulation methods. The tumorto-dose-limiting-organ (bone marrow) absorbed dose ratio, that is, the therapeutic index, was higher in the THW-aided than rhTSH-aided administrations. Additional comparison for tumor and normal organ absorbed dose in patients prepared using both methods is needed before definitive conclusions may be drawn regarding rhTSH versus THW patient preparation methods for 131 I therapy of metastatic DTC.

PEGylated polycation/DNA micellar nanoparticles have been developed that can undergo shape transformation upon cleavage of the PEG grafts in response to an environmental cue. As a proof-of-principle, DNA nanoparticles with higher PEG grafting density adopting long, worm- and rod-like morphologies, transition to more condensed nanoparticles with spherical and short-rod morphologies upon cleavage of a fraction of the PEG grafts from the copolymer. This shape transformation leads to increased surface charges, correlating with improved transfection efficiency.

Nanoparticles formed through complexation of plasmid DNA and copolymers are promising gene-delivery vectors, offering a wide range of advantages over alternative delivery strategies. Notably, recent research has shown that the shape of these particles can be tuned, which makes it possible to gain understanding of their shape-dependent transfection properties. Whereas earlier methods achieved shape tuning through the use of block copolymers and variation of solvent polarity, here we demonstrate through a combined experimental and computational approach that the same degree of shape control can be achieved through the use of graft copolymers that are easier to synthesize and provide a wider range of parameters for shape control. Moreover, the approach presented here does not require the use of organic solvents. The simulation work provides insight into the mechanism governing the shape variation as well as an effective model to guide further design of non-viral gene-delivery vectors. Our experimental findings offer important opportunities for the facile and large-scale synthesis of biocompatible gene-delivery vectors with well-controlled shape and tunable transfection properties. The in vitro study shows that both micelle shape and transfection efficiency are strongly correlated with the key structural parameters of the graft copolymer carriers.

We study the annihilation of topological solitons in the simplest setting: a one-dimensional ferromagnet with an easy axis. We develop an effective theory of the annihilation process in terms of four collective coordinates: two zero modes of the translational and rotational symmetries Z and Φ, representing the average position and azimuthal angle of the two solitons, and two conserved momenta ζ and ϕ, representing the relative distance and twist. Comparison with micromagnetic simulations shows that our approach captures well the essential physics of the process.The dynamics of topological solitons in ferromagnets [1] poses a class of problems of fundamental interest. Time evolution of magnetization is governed by the Landau-Lifshitz-Gilbert (LLG) equation [2,3] Here m(r, t) = M/|M| is the unit-vector field of magnetization, J = |M|/γ is the angular momentum density, h eff (r) = −δU/δm(r) is the effective magnetic field obtained from the potential energy functional U [m(r)] and α 1 is the Gilbert damping constant. Since the magnetization field has infinitely many modes that are coupled non-linearly, full analytic solution to a dynamical problem is unavailable in most cases.A powerful alternative approach is to identify a small number of relevant soft modes, parametrized in terms of collective coordinates, and formulate an effective theory only in terms of these. This method was first applied to magnetic solitons by Schryer and Walker [4] to describe the dynamics of a domain wall in an easy-axis ferromagnet in one spatial dimension, m = m(z, t), with the Lagrangian [1]and the potential energyHere θ and φ are the polar and azimuthal angles of magnetization m, A is the exchange constant, K is the anisotropy, andẑ is the direction of the easy axis. The unit of length is the width of the domain wall 0 = A/K and the unit of time is the inverse of the ferromagnetic resonance frequency,In what follows, we work in these natural units and set J = A = K = 0 = t 0 = 1. A topological soliton interpolating between the two ground states m = ±ẑ and minimizing the potential energy (3) is a domain wallThe position of a domain wall Z and its azimuthal angle Φ are collective coordinates describing the zero modes associated with the translational and rotational symmetries. Schryer and Walker showed that, in the presence of weak perturbations, the dynamics of a domain wall reduces to a time evolution of Z and Φ. By substituting the domain-wall Ansatz (4) into the LLG equation (1) or into the Lagrangian (2), one obtains an effective theory for this system in terms of the two collective coordinates arXiv:1702.02248v1 [cond-mat.mes-hall]