Studies of radioactive cisplatin (191Pt) for tumour imaging and therapy
(2000)- Abstract
- A radioactive variant of the cytostatic agent cis-dichlorodiammineplatinum(II), cisplatin, was synthesised from 191PtCl4. The 191Pt-cisplatin was found to be a sterile product of high radionuclide, radiochemical and chemical purity. The pharmacokinetics of platinum in tumour tissue and organs at risk of fourteen patients undergoing treatment with cisplatin were studied by exchanging a small fraction of the prescribed amount of cisplatin with 191Pt-cisplatin. The uptake and retention of platinum were investigated by gamma camera measurements up to ten days after infusion of 191Pt-cisplatin. Highest concentration of platinum was found in the liver, on average 5.7 ± 0.5 mikrog/g normalised to a given amount of 180 mg cisplatin. Corresponding... (More)
- A radioactive variant of the cytostatic agent cis-dichlorodiammineplatinum(II), cisplatin, was synthesised from 191PtCl4. The 191Pt-cisplatin was found to be a sterile product of high radionuclide, radiochemical and chemical purity. The pharmacokinetics of platinum in tumour tissue and organs at risk of fourteen patients undergoing treatment with cisplatin were studied by exchanging a small fraction of the prescribed amount of cisplatin with 191Pt-cisplatin. The uptake and retention of platinum were investigated by gamma camera measurements up to ten days after infusion of 191Pt-cisplatin. Highest concentration of platinum was found in the liver, on average 5.7 ± 0.5 mikrog/g normalised to a given amount of 180 mg cisplatin. Corresponding value for the kidneys was 1.9 ± 0.3 mikrog/g. Uptake of platinum in tumours was visualised in five patients with an average maximum concentration of 4.9 ± 1.0 mikrog/g normalised to a given amount of 180 mg cisplatin. The data from the pharmacokinetic study was used together with data from the literature to estimate the absorbed dose and effective dose to patients receiving radioactive cisplatin. The effective doses were calculated to be 0.10 ± 0.02 mSv/MBq, 0.17 ± 0.04 mSv/MBq and 0.23± 0.05 mSv/MBq for 191Pt-, 193mPt-, and 195mPt-cisplatin respectively. The combined effect of the radio- and chemotoxicity from 191Pt-cisplatin was investigated both in vitro and in vivo. A cervical cancer cell line was incubated with cisplatin or 191Pt-cisplatin with various concentrations and specific activities. It was shown that the surviving fraction was smaller for cells treated with 191Pt-cisplatin than for cells treated with the same concentration of non-radioactive cisplatin. The surviving fraction decreased with increasing specific activity. Isobologram technique showed that the radio- and chemotoxicity interacted in a supra-additive (synergistic) manner. In an in vivo model, nude mice with xenografted tumours were given physiological saline (controls), cisplatin or 191Pt-cisplatin. The growth was significantly more retarded for the tumours on the mice given 191Pt-cisplatin compared with the tumours on the other mice. No significant change in general toxic effect, manifested as weight change or mortality, could be detected between the groups of mice given cisplatin and 191Pt-cisplatin respectively. 191Pt-cisplatin was shown to be a radiopharmaceutical suitable for both tumour imaging and therapy. There is potential for an increased use of radioactive cisplatin in the future. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/40261
- author
- Areberg, Johan LU
- supervisor
- opponent
-
- Carlsson, Jörgen
- organization
- publishing date
- 2000
- type
- Thesis
- publication status
- published
- subject
- keywords
- Cytology, mice, in vitro, gamma camera, tumour imaging, platinum pharmacokinetics, cisplatin, radioactive, oncology, cancerology, Cytologi, onkologi, cancer
- pages
- 60 pages
- publisher
- Radiaiton Physics, Malmö University Hospital, SE-205 02 Malmö, Sweden
- defense location
- MFC, Malmö University Hospital
- defense date
- 2000-02-25 09:15:00
- external identifiers
-
- other:ISRN: LUNFD6/NFRF- - 00/1011 - - SE
- ISBN
- 91-628-3989-6
- language
- English
- LU publication?
- yes
- id
- 8ec80c86-5a99-4e1a-a6d7-350b4a4fcc12 (old id 40261)
- date added to LUP
- 2016-04-04 10:53:47
- date last changed
- 2018-11-21 21:01:25
@phdthesis{8ec80c86-5a99-4e1a-a6d7-350b4a4fcc12,
abstract = {{A radioactive variant of the cytostatic agent cis-dichlorodiammineplatinum(II), cisplatin, was synthesised from 191PtCl4. The 191Pt-cisplatin was found to be a sterile product of high radionuclide, radiochemical and chemical purity. The pharmacokinetics of platinum in tumour tissue and organs at risk of fourteen patients undergoing treatment with cisplatin were studied by exchanging a small fraction of the prescribed amount of cisplatin with 191Pt-cisplatin. The uptake and retention of platinum were investigated by gamma camera measurements up to ten days after infusion of 191Pt-cisplatin. Highest concentration of platinum was found in the liver, on average 5.7 ± 0.5 mikrog/g normalised to a given amount of 180 mg cisplatin. Corresponding value for the kidneys was 1.9 ± 0.3 mikrog/g. Uptake of platinum in tumours was visualised in five patients with an average maximum concentration of 4.9 ± 1.0 mikrog/g normalised to a given amount of 180 mg cisplatin. The data from the pharmacokinetic study was used together with data from the literature to estimate the absorbed dose and effective dose to patients receiving radioactive cisplatin. The effective doses were calculated to be 0.10 ± 0.02 mSv/MBq, 0.17 ± 0.04 mSv/MBq and 0.23± 0.05 mSv/MBq for 191Pt-, 193mPt-, and 195mPt-cisplatin respectively. The combined effect of the radio- and chemotoxicity from 191Pt-cisplatin was investigated both in vitro and in vivo. A cervical cancer cell line was incubated with cisplatin or 191Pt-cisplatin with various concentrations and specific activities. It was shown that the surviving fraction was smaller for cells treated with 191Pt-cisplatin than for cells treated with the same concentration of non-radioactive cisplatin. The surviving fraction decreased with increasing specific activity. Isobologram technique showed that the radio- and chemotoxicity interacted in a supra-additive (synergistic) manner. In an in vivo model, nude mice with xenografted tumours were given physiological saline (controls), cisplatin or 191Pt-cisplatin. The growth was significantly more retarded for the tumours on the mice given 191Pt-cisplatin compared with the tumours on the other mice. No significant change in general toxic effect, manifested as weight change or mortality, could be detected between the groups of mice given cisplatin and 191Pt-cisplatin respectively. 191Pt-cisplatin was shown to be a radiopharmaceutical suitable for both tumour imaging and therapy. There is potential for an increased use of radioactive cisplatin in the future.}},
author = {{Areberg, Johan}},
isbn = {{91-628-3989-6}},
keywords = {{Cytology; mice; in vitro; gamma camera; tumour imaging; platinum pharmacokinetics; cisplatin; radioactive; oncology; cancerology; Cytologi; onkologi; cancer}},
language = {{eng}},
publisher = {{Radiaiton Physics, Malmö University Hospital, SE-205 02 Malmö, Sweden}},
school = {{Lund University}},
title = {{Studies of radioactive cisplatin (191Pt) for tumour imaging and therapy}},
year = {{2000}},
}