Advanced

Reduced myelotoxicity with sustained tumor concentration of radioimmunoconjugates in rats after extracorporeal depletion.

Mårtensson, Linda LU ; Nilsson, Rune; Ohlsson, Tomas G LU ; Sjögren, Hans Olov LU ; Strand, Sven-Erik LU and Tennvall, Jan LU (2007) In Journal of Nuclear Medicine 48(2). p.269-276
Abstract
The aim of this study was to evaluate the possibility of decreasing the myelotoxicity associated with radioimmunotherapy (RIT) by extracorporeal depletion of radioimmunoconjugates (RIC) from the circulation. The optimal combination of radionuclide and the time interval between injection of the RIC and the subsequent extracorporeal depletion procedure was assessed in immunocompetent rats, with respect to both myelotoxicity and tumor concentration of RIC. Methods: Rats were injected with (177)tumor Y-90-labeled antibody conjugate (mAb-DOTA-biotin) (mAb is monoclonal antibody; DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid) and subjected to removal of the conjugate from the circulation by extracorporeal affinity... (More)
The aim of this study was to evaluate the possibility of decreasing the myelotoxicity associated with radioimmunotherapy (RIT) by extracorporeal depletion of radioimmunoconjugates (RIC) from the circulation. The optimal combination of radionuclide and the time interval between injection of the RIC and the subsequent extracorporeal depletion procedure was assessed in immunocompetent rats, with respect to both myelotoxicity and tumor concentration of RIC. Methods: Rats were injected with (177)tumor Y-90-labeled antibody conjugate (mAb-DOTA-biotin) (mAb is monoclonal antibody; DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid) and subjected to removal of the conjugate from the circulation by extracorporeal affinity adsorption treatment (ECAT) 12, 24, or 48 h after injection. Myelotoxicity was assessed by analysis of blood parameters for 10 wk. The effect of ECAT on the tumor concentration of RIC was evaluated in parallel by scintillation camera imaging in rats injected with In-111-labeled RIC. Results: ECAT reduced the blood content of RIC by 95%. Thus, myelotoxicity was significantly milder in animals subjected to ECAT than that in controls. The timing of ECAT influenced the rate and level of bone marrow recovery, with an earlier recovery in animals subjected to ECAT early after injection. The toxicity-reducing effect of ECAT was more distinct in animals injected with Lu-177-labeled RIC than in animals injected with 90Y-labeled RIC. Scintillation camera imaging of tumors before and after ECAT revealed that subjecting animals to ECAT at 12 h after injection considerably reduced the total activity in tumors (34%), whereas the effect was lower at both 24 h (18%) and 48 h (18%) after injection. Conclusion: ECAT can efficiently reduce myelotoxicity associated with RIT, and the concentration of RIC in tumor can be sustained, provided ECAT is performed at an optimal time after antibody administration. The choice of radionuclide for RIT in combination with ECAT is important, as the physical half-life is crucial for the toxicity-reducing potential of ECAT at a specific time. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
oncology, antibody, radionuclide therapy, radioimmunotherapy, syngeneic, tumor model
in
Journal of Nuclear Medicine
volume
48
issue
2
pages
269 - 276
publisher
Society of Nuclear Medicine
external identifiers
  • wos:000244115600034
  • scopus:34047201766
ISSN
0161-5505
language
English
LU publication?
yes
id
7521ef39-beba-40e9-b8d0-80e4d6f4d09d (old id 165982)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17268025&dopt=Abstract
date added to LUP
2007-07-16 12:50:25
date last changed
2017-01-01 07:25:31
@article{7521ef39-beba-40e9-b8d0-80e4d6f4d09d,
  abstract     = {The aim of this study was to evaluate the possibility of decreasing the myelotoxicity associated with radioimmunotherapy (RIT) by extracorporeal depletion of radioimmunoconjugates (RIC) from the circulation. The optimal combination of radionuclide and the time interval between injection of the RIC and the subsequent extracorporeal depletion procedure was assessed in immunocompetent rats, with respect to both myelotoxicity and tumor concentration of RIC. Methods: Rats were injected with (177)tumor Y-90-labeled antibody conjugate (mAb-DOTA-biotin) (mAb is monoclonal antibody; DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid) and subjected to removal of the conjugate from the circulation by extracorporeal affinity adsorption treatment (ECAT) 12, 24, or 48 h after injection. Myelotoxicity was assessed by analysis of blood parameters for 10 wk. The effect of ECAT on the tumor concentration of RIC was evaluated in parallel by scintillation camera imaging in rats injected with In-111-labeled RIC. Results: ECAT reduced the blood content of RIC by 95%. Thus, myelotoxicity was significantly milder in animals subjected to ECAT than that in controls. The timing of ECAT influenced the rate and level of bone marrow recovery, with an earlier recovery in animals subjected to ECAT early after injection. The toxicity-reducing effect of ECAT was more distinct in animals injected with Lu-177-labeled RIC than in animals injected with 90Y-labeled RIC. Scintillation camera imaging of tumors before and after ECAT revealed that subjecting animals to ECAT at 12 h after injection considerably reduced the total activity in tumors (34%), whereas the effect was lower at both 24 h (18%) and 48 h (18%) after injection. Conclusion: ECAT can efficiently reduce myelotoxicity associated with RIT, and the concentration of RIC in tumor can be sustained, provided ECAT is performed at an optimal time after antibody administration. The choice of radionuclide for RIT in combination with ECAT is important, as the physical half-life is crucial for the toxicity-reducing potential of ECAT at a specific time.},
  author       = {Mårtensson, Linda and Nilsson, Rune and Ohlsson, Tomas G and Sjögren, Hans Olov and Strand, Sven-Erik and Tennvall, Jan},
  issn         = {0161-5505},
  keyword      = {oncology,antibody,radionuclide therapy,radioimmunotherapy,syngeneic,tumor model},
  language     = {eng},
  number       = {2},
  pages        = {269--276},
  publisher    = {Society of Nuclear Medicine},
  series       = {Journal of Nuclear Medicine},
  title        = {Reduced myelotoxicity with sustained tumor concentration of radioimmunoconjugates in rats after extracorporeal depletion.},
  volume       = {48},
  year         = {2007},
}