Sökning: WFRF:(Jacobsson Lars 1947) >
Therapeutic efficac...
Therapeutic efficacy and tumor dose estimations in radioimmunotherapy of intraperitoneally growing OVCAR-3 cells in nude mice with (211)At-labeled monoclonal antibody MX35
-
- Elgqvist, Jörgen, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för radiofysik,Institute of Selected Clinical Sciences, Department of Radiation Physics
-
- Andersson, Håkan, 1944 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för onkologi,Institute of Selected Clinical Sciences, Department of Oncology
-
- Bäck, Tom, 1964 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för radiofysik,Institute of Selected Clinical Sciences, Department of Radiation Physics
-
visa fler...
-
- Hultborn, Ragnar, 1946 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för onkologi,Institute of Selected Clinical Sciences, Department of Oncology
-
Jensen, H. (författare)
-
- Karlsson, Börje (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för radiofysik,Institute of Selected Clinical Sciences, Department of Radiation Physics
-
- Lindegren, Sture, 1960 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för radiofysik,Institute of Selected Clinical Sciences, Department of Radiation Physics
-
- Palm, Stig, 1964 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för radiofysik,Institute of Selected Clinical Sciences, Department of Radiation Physics
-
- Warnhammar Finnborg, Elisabet, 1942 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för onkologi,Institute of Selected Clinical Sciences, Department of Oncology
-
- Jacobsson, Lars, 1947 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för särskilda specialiteter, Avdelningen för radiofysik,Institute of Selected Clinical Sciences, Department of Radiation Physics
-
visa färre...
-
(creator_code:org_t)
- 2005
- 2005
- Engelska.
-
Ingår i: J Nucl Med. - 0161-5505. ; 46:11, s. 1907-15
- Relaterad länk:
-
https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- The purpose of this study was to investigate the therapeutic efficacy of-and to estimate the absorbed dose to-tumor cells from radioimmunotherapy (RIT) in an ovarian cancer model using the alpha-particle-emitting nuclide (211)At labeled to monoclonal antibody (mAb) MX35. Previous studies on mAb MOv18 did not allow for dosimetry because of antigen shedding in vitro. METHODS: Five-week-old female nude BALB/c nu/nu mice were inoculated intraperitoneally with 1 x 10(7) cells of the human tumor cell line OVCAR-3. Three weeks later, the animals were given approximately 400, 800, or 1,200 kBq of (211)At-labeled mAb MX35 intraperitoneally. As controls, one group of animals was injected with unlabeled mAb and another group was injected with phosphate-buffered saline (PBS). Another group was given approximately 400 kBq of (211)At labeled to the previously investigated mAb MOv18 for efficacy comparison. Two months after treatment, the animals were sacrificed and the presence of macroscopic and microscopic tumors, as well as ascites, was determined. The absorbed dose to tumor cells on the peritoneal surface was estimated in terms of the sum of a specific and a nonspecific contribution. The specific contribution, arising from mAbs binding to the antigenic sites on the cell membrane, was calculated using a dynamic compartment model developed in-house and Monte Carlo software. The model used as input values the number of mAbs injected into the abdominal cavity, N(mAb), the specific activity, A(sp), the association rate constant, k(on), and the maximal number of mAbs bound per cell, B(max)-all determined by in vitro experiments. This specific component of the absorbed dose was calculated for assumed cell cluster sizes with radii of 25, 50, and 100 microm. The nonspecific contribution to the absorbed dose was derived from unbound mAbs freely circulating in the abdominal cavity, also using the Monte Carlo software. RESULTS: In the control groups given unlabeled MX35 or PBS, all 18 animals had ascites, 6 of 9 animals in each group had macroscopic tumors, and all animals had microscopic growth. In the 3 groups given different amounts of (211)At-MX35, only 3 of 25 animals developed ascites. None of these animals had any sign of macroscopic tumors, but 8 had microscopic growth. In the group given (211)At-MOv18, no animals had ascites or macroscopic tumors, but 3 of 10 animals had microscopic tumors. After injecting 400 kBq of (211)At-MX35, the absorbed dose due to specific binding, for a cell cluster with a radius of 50 microm, ranged from 413 to 223 Gy between 0- and 45-microm distance from the cluster center, assuming a homogeneous distribution of (211)At-MX35 in the cluster. The contribution from unbound (211)At-MX35 and (211)At-MX35 only distributed on the cluster surface, for this cluster size, ranged from 7 to 14 Gy and from 29 to 94 Gy, between 0- and 45-microm distance from the cluster center, respectively. The calculated total absorbed doses are in a clinically relevant range and were effective as verified in the nude mice with subclinical intraperitoneal growth of OVCAR-3 cells. CONCLUSION: (211)At-MX35 injected intraperitoneally exhibits a high efficacy when treating micrometastatic growth of the ovarian cancer cell line OVCAR-3 on the peritoneum of nude mice.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Animals
- Antibodies
- Monoclonal/ pharmacokinetics/ therapeutic use
- Body Burden
- Cell Line
- Tumor
- Female
- Humans
- Mice
- Mice
- Inbred BALB C
- Mice
- Nude
- Organometallic Compounds/ pharmacokinetics/ therapeutic use
- Ovarian Neoplasms/ metabolism/pathology/ radiotherapy
- Peritoneal Neoplasms/metabolism/pathology/radiotherapy
- Radiometry/methods
- Radiopharmaceuticals/ pharmacokinetics/ therapeutic use
- Radiotherapy Dosage
- Treatment Outcome
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Elgqvist, Jörgen ...
-
Andersson, Håkan ...
-
Bäck, Tom, 1964
-
Hultborn, Ragnar ...
-
Jensen, H.
-
Karlsson, Börje
-
visa fler...
-
Lindegren, Sture ...
-
Palm, Stig, 1964
-
Warnhammar Finnb ...
-
Jacobsson, Lars, ...
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Radiologi och bi ...
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Cancer och onkol ...
- Artiklar i publikationen
-
J Nucl Med
- Av lärosätet
-
Göteborgs universitet