Diffusivity Characteristics Of Glucose In Alginate Immobilization Matrices

Conventional techniques of measuring diffusivity (D{dollar}\sb{lcub}\rm e{rcub}{dollar}) in gel entrapment matrices are not practical due to the poor mechanical stability of such solids. A novel apparatus was therefore designed to measure D{dollar}\sb {lcub}\rm e{rcub}{dollar} and partition coefficient (K{dollar}\sb{lcub}\rm p{rcub}){dollar} of glucose in alginate gels using radiotracer techniques. In this method, a specially prepared, large, spherical alginate bead was mounted to a stainless-steel rod and the sphere immersed in a liquid phase of limited volume. By rotating the bead at high angular velocities, the rate of C{dollar}\sp{lcub}14{rcub}{dollar}-glucose uptake or release was measured using a scintillation spectrometer, under conditions of near ideal mixing and negligible film mass transfer resistance. A model equation describing unsteady-state mass transfer in a sphere immersed in a liquid phase of limited volume was used to evaluate D{dollar}\sb{lcub}\rm e{rcub}{dollar}.;When the initial glucose concentration in the liquid phase was increased from 3 to 300 kg.m{dollar}\sp{lcub}-3{rcub}{dollar}, an exponential increase in D{dollar}\sb{lcub}\rm e{rcub}{dollar} values was observed. However, at all concentrations the ratio D{dollar}\sb{lcub}\rm e{rcub}{dollar}/D was constant at 0.91 where D is the free-phase diffusivity of glucose in water. The temperature dependence of D{dollar}\sb{lcub}\rm e{rcub}{dollar} obeyed the Arrhenius relationship and the activation energy for diffusion of glucose in cell-free and cell-occupied (118 kg dry weight/m{dollar}\sp 3{dollar} of gel) Ca-alginate beads was found to be 21.3 and 20.1 kJ.mol{dollar}\sp{lcub}-1{rcub}{dollar}, respectively.;Increase in the concentration of either Ca-alginate, chelating agent (CaCl{dollar}\sb 2{dollar} or BaCl{dollar}\sb 2{dollar}), or entrapped yeast cells, all caused significant reductions in the values of D{dollar}\sb{lcub}\rm e{rcub}{dollar}.;Attempts were made to develop appropriate correlations for predicting D{dollar}\sb{lcub}\rm e{rcub}{dollar} and suitable literature correlations tested whenever possible. The significance of the data reported in this study was assessed in terms of the stability characteristics of the alginate gel matrix and the reported kinetic properties of entrapped cells

Intratumoral Delivery of MDNA55, an Interleukin-4 Receptor Targeted Immunotherapy, by MRI-Guided Convective Delivery for the Treatment of Recurrent Glioblastoma

https://digitalcommons.psjhealth.org/other_pubs/1047/thumbnail.jp

Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma

PurposeThe current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM).Patients and methodsA total of 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and centrally by an independent radiologic faculty, then standard RANO, iRANO, and mRANO criteria were applied.ResultsA total of 41 of 47 patients (mean age 56 ± 11.7) were evaluable for response. PFS was significantly shorter using standard RANO compared with iRANO (log-rank, P < 0.0001; HR = 0.3) and mRANO (P < 0.0001; HR = 0.3). In patients who died and had confirmed progression on standard RANO, no correlation was observed between PFS and OS (local, P = 0.47; central, P = 0.34). Using iRANO, a weak association was observed between confirmed PFS and OS via local site measurements (P = 0.017), but not central measurements (P = 0.18). A total of 24 of 41 patients (59%) were censored using iRANO and because they lacked confirmation of progression 3 months after initial progression. A strong correlation was observed between mRANO PFS and OS for both local (R2 = 0.66, P < 0.0001) and centrally determined reads (R2 = 0.57, P = 0.0007).ConclusionsNo correlation between radiographic PFS and OS was observed for standard RANO or iRANO, but a correlation was observed between PFS and OS using the mRANO criteria. Also, the iRANO criteria was difficult to implement due to need to confirm progression 3 months after initial progression, censoring more than half the patients

Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma.

PURPOSE: The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM). PATIENTS AND METHODS: A total of 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and centrally by an independent radiologic faculty, then standard RANO, iRANO, and mRANO criteria were applied. RESULTS: A total of 41 of 47 patients (mean age 56 ± 11.7) were evaluable for response. PFS was significantly shorter using standard RANO compared with iRANO (log-rank, CONCLUSIONS: No correlation between radiographic PFS and OS was observed for standard RANO or iRANO, but a correlation was observed between PFS and OS using the mRANO criteria. Also, the iRANO criteria was difficult to implement due to need to confirm progression 3 months after initial progression, censoring more than half the patients