Changes in Lognormal Shape Parameter Guide Design of Patient-Specific Radiochemotherapy Cocktails

The Advantage of Antibody Cocktails for Targeted Alpha Therapy Depends on Specific Activity

“…5A); note that these curves begin to saturate at about 1.0 mg/mL as well. This parallels observations made by Akudugu et al when MDA-MB-231 cells were treated with doxorubicin, daunomycin, and 210 Po-citrate (16). The saturation in the Ab4 curve occurred despite the linear increase in mean antibody binding over the entire concentration range studied.…”

“…The cell culture protocol followed that of Akudugu et al (6,15,16). Briefly, MDA-MB-231-luc-D3H1 (MDA-MB-231) human breast cancer cells (Caliper Life Sciences) were grown in minimum essential medium (Cellgro catalog number 10-010-CV).…”

NVP-BEZ235 Enhances Radiosensitivity of Human Prostate Cancer Cells but Acts as a Radioprotector to Normal Prostate Cells

“…Targeting of single signaling components often does not result in optimal cytotoxicity. This is partly due to non-uniform distributions of target antigen expression in cell populations, which may limit the ability to target all cells with toxic levels of therapeutic agents [14][15][16]. Therefore, developing therapeutic approaches that concomitantly target multiple signaling components of the EGFR and PI3K pathways might significantly sensitise prostate cancer cells to radiotherapy and improve treatment outcome.…”

Cell-Level Dosimetry and Biologic Response Modeling of Heterogeneously Distributed Radionuclides: A Step Forward

“…Novel features of this cell culture model and dosimetric analysis include a structurally heterogeneous, more realistic milieu comprising water-equivalent cells, a Cytomatrix carbon scaffold (mass density, 2 gÁcm 23 ) in the form of irregular ligaments, and a water-filled extracellular space; empirically validated modeling of the differential radiobiologic effectiveness between cell selfand cross-doses (corresponding to mean lethal doses D 37 of 400 and 120 cGy, respectively, for low-linearenergy-transfer radiations) (21-23); and a lognormal distribution of activity among cells, with quantitative assessment of the effect on overall survival of varying degrees of nonuniformity of the activity per cell (i.e., corresponding to values of 0.6, 1.0, and 2.0 of the so-called shape parameter s of the lognormal probability density function) (22,24,25). On the basis of the calculated cell nuclei doses and previously published models of cell killing, survival curves were derived and characterized in relation to the electron energy and the nonuniformity of the activity distribution.…”

“…Projecting forward, a catalog of shape parameter values for different histologic types of tumors and different radiopharmaceuticals could perhaps be compiled by quantitative autoradiography of tumor specimens surgically harvested after tracer administrations to a limited number of patients. The individually optimized radionuclide or cocktail of radionuclides (25), tumor dose, and administered activity could then be prescribed for a patient's specific histologic tumor type (i.e., shape parameter value) using mean tumor doses per unit of administered activity derived on a case-by-case basis from routine quantitative imaging studies. With increasingly realistic dosimetric analyses-such as the method proposed by Rajon et al (11)-and the biologic insights they provide, such a hypothetical leap forward warrants at least some consideration.…”