scholarly journals A Three-Compartment Pharmacokinetic Model to Predict the Interstitial Concentration of Talaporfin Sodium in the Myocardium for Photodynamic Therapy: A Method Combining Measured Fluorescence and Analysis of the Compartmental Origin of the Fluorescence

2018 ◽  
Vol 6 (1) ◽  
pp. 1
Author(s):  
Yuko Uno ◽  
Emiyu Ogawa ◽  
Eitaro Aiyoshi ◽  
Tsunenori Arai

To evaluate the effectiveness of photodynamic therapy occurring in the interstitial space of the myocardium, we estimated the interstitial concentration of talaporfin sodium in the canine myocardium by constructing a three-compartment pharmacokinetic model based on measured changes in talaporfin sodium plasma concentration and myocardial fluorescence. Differential rate equations of talaporfin sodium concentration in the plasma, interstitial space, and cell compartment were developed with individual compartment volume, concentration, and rate constants. Using measured volume ratios based on histological examinations, we defined that the myocardial fluorescence consisted of the linear addition of fluorescence generated from these three compartments. The rate constants were obtained by fitting to minimize the sum of the squared errors between the measured talaporfin sodium concentrations and the calculated concentrations divided by the number of data points using the conjugate gradient method in MATLAB. We confirmed that this fitting operation may be appropriate, because a coefficient of determination between the measured talaporfin sodium changes and the calculated concentrations using our equations was 0.99. Consequently, to estimate the interstitial concentration in the canine myocardium, we propose a three-compartment pharmacokinetic model construction methodology using measured changes in talaporfin sodium plasma concentration and changes in myocardial fluorescence.

Esophagus ◽  
2020 ◽  
Author(s):  
Tomoyuki Hayashi ◽  
Yoshiro Asahina ◽  
Hiroyoshi Nakanishi ◽  
Takeshi Terashima ◽  
Koichi Okamoto ◽  
...  

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e103126 ◽  
Author(s):  
Shinya Ohashi ◽  
Osamu Kikuchi ◽  
Mihoko Tsurumaki ◽  
Yukie Nakai ◽  
Hiroi Kasai ◽  
...  

2008 ◽  
Vol 1784 (9) ◽  
pp. 1192-1199 ◽  
Author(s):  
Tooru Nakamura ◽  
Miyo Sakai ◽  
Yutaka Sadakane ◽  
Tatsuya Haga ◽  
Yuji Goto ◽  
...  

Lung Cancer ◽  
2007 ◽  
Vol 58 (3) ◽  
pp. 317-323 ◽  
Author(s):  
Jitsuo Usuda ◽  
Hidemitsu Tsutsui ◽  
Hidetoshi Honda ◽  
Shuji Ichinose ◽  
Taichirou Ishizumi ◽  
...  

2019 ◽  
Vol 34 (2) ◽  
pp. 899-906 ◽  
Author(s):  
Tatsunori Minamide ◽  
Yusuke Yoda ◽  
Keisuke Hori ◽  
Kensuke Shinmura ◽  
Yasuhiro Oono ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3641
Author(s):  
Tatsuya Kobayashi ◽  
Makoto Miyazaki ◽  
Nobuyoshi Sasaki ◽  
Shun Yamamuro ◽  
Eita Uchida ◽  
...  

To manage refractory and invasive glioblastomas (GBM)s, photodynamic therapy (PDT) using talaporfin sodium (NPe6) (NPe6-PDT) was recently approved in clinical practice. However, the molecular machineries regulating resistance against NPe6-PDT in GBMs and mechanisms underlying the changes in GBM phenotypes following NPe6-PDT remain unknown. Herein, we established an in vitro NPe6-mediated PDT model using human GBM cell lines. NPe6-PDT induced GBM cell death in a NPe6 dose-dependent manner. However, this NPe6-PDT-induced GBM cell death was not completely blocked by the pan-caspase inhibitor, suggesting NPe6-PDT induces both caspase-dependent and -independent cell death. Moreover, treatment with poly (ADP-ribose) polymerase inhibitor blocked NPe6-PDT-triggered caspase-independent GBM cell death. Next, it was also revealed resistance to re-NPe6-PDT of GBM cells and GBM stem cells survived following NPe6-PDT (NPe6-PDT-R cells), as well as migration and invasion of NPe6-PDT-R cells were enhanced. Immunoblotting of NPe6-PDT-R cells to assess the behavior of the proteins that are known to be stress-induced revealed that only ERK1/2 activation exhibited the same trend as migration. Importantly, treatment with the MEK1/2 inhibitor trametinib reversed resistance against re-NPe6-PDT and suppressed the enhanced migration and invasion of NPe6-PDT-R cells. Overall, enhanced ERK1/2 activation is suggested as a key regulator of elevated malignant phenotypes of GBM cells surviving NPe6-PDT and is therefore considered as a potential therapeutic target against GBM.


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