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Internal dosimetry. Macroscopic, small-scale and microscopic perspectives

Hindorf, Cecilia LU (2004)
Abstract (Swedish)
Popular Abstract in Swedish

Interndosimetri ur ett makroskopiskt och mikroskopiskt perspektiv



Med interndosimetri menas den metod man använder för att bestämma en absorberad dos till en vävnad för ett radioaktivt ämne som är fördelat i kroppen. Absorberad dos, dvs den av strålningen deponerade energin per massenhet, mäts i enheten gray (1 J/kg = 1 Gy) och kan beräknas med ekvationerna som syns på omslaget. Absorberad dos har i många sammanhang visat sig vara en storhet som kan relateras till den biologiska effekt som strålningen orsakar.



Den vävnad i kroppen som är mest strålningskänslig är benmärgen. I benmärgen produceras nästan alla våra blodkroppar (röda, vita och blodplättar) och... (More)
Popular Abstract in Swedish

Interndosimetri ur ett makroskopiskt och mikroskopiskt perspektiv



Med interndosimetri menas den metod man använder för att bestämma en absorberad dos till en vävnad för ett radioaktivt ämne som är fördelat i kroppen. Absorberad dos, dvs den av strålningen deponerade energin per massenhet, mäts i enheten gray (1 J/kg = 1 Gy) och kan beräknas med ekvationerna som syns på omslaget. Absorberad dos har i många sammanhang visat sig vara en storhet som kan relateras till den biologiska effekt som strålningen orsakar.



Den vävnad i kroppen som är mest strålningskänslig är benmärgen. I benmärgen produceras nästan alla våra blodkroppar (röda, vita och blodplättar) och det innebär att den producerar ca 500 g blodkroppar per dygn. När benmärgen skadas sjunker antalet blodkroppar som cirkulerar i blodet och detta kan mätas genom ett vanligt blodprov.



Vid radionuklidterapi används ett radioaktivt läkemedel som behandling för olika sjukdomar. Den vanligaste formen av radionuklidterapi är en behandling med radioaktivt jod (131I) av en patient med en sköldkörtel som producerar för mycket hormon (hypertyreotoxikos). Patienten genomgår undersökningar där man bestämmer den fysiologiska storleken av sköldkörteln (den del av skölkörteln som producerar hormoner och därmed tar upp jod) och hur stor andel av det jod som man får att dricka som söker sig till sköldkörteln. Utifrån vilken sjukdom som diagnostiserats, ordinerar läkaren en absorberad dos till sköldkörteln och utifrån mätningarna beräknar fysikern hur mycket jod (hur stor aktivitet) som patienten skall dricka för att återigen få en normalt fungerande sköldkörtel. Vid radioimmunoterapi (RIT), som är en form av radionuklidterapi, kopplas en radionuklid kemiskt till en tumörsökande antikropp. RIT är en behandlingsmetod som visat sig vara speciellt lämpad för behandling av vissa strålningskänsliga typer av lymfom (en typ av cancer). För att kunna ge en så bra RIT-behandling som möjligt vill man ge patienten en så stor absorberad dos till tumören som möjligt och en så liten absorberad dos som möjligt till benmärg.



I en scintillationskamera-bild (bilden till vänster på omslaget) ser det ut som om aktiviteten fördelar sig ganska jämnt i tumören, men om man tar sig en närmare titt så är det inte så. I den övre bilden till höger kan man se att aktiviteten, de mörka områdena, i själv verket fördelar sig ojämnt i tumören och inte ens på cellnivå är aktiviteten jämnt fördelad (teckningen nere till höger, där atomerna symboliseras av de röda cirklarna och antikropparna är ritade som Y). Denna ojämna aktivitets-fördelning, i både tid och rum, ställer stora krav på hur man skall beräkna absorberad dos eftersom den makroskopiska absorberade dosen inte behöver stämma överens med den mikroskopiskt beräknade absorberade dosen.



Det är denna problematik som diskuteras i denna avhandling. Hur man skall beräkna absorberad dos, hur man skall kunna relatera absorberad dos till biologisk effekt och hur man skall kunna optimera radioimmunoterapi för patienter med lymfom. (Less)
Abstract
Internal dosimetry deals with the assessment of absorbed dose for radionuclides distributed inside the body. The absorbed dose is in its turn used for correlation with the biological effect caused by the irradiation. In radioimmunotherapy is however the correlation not easily found and factors influencing this are evaluated and discussed in this work. The internal dosimetry could be subdivided into three levels; macroscopic, small-scale, and microscopic dosimetry. Macroscopic dosimetry: The MIRD S formalism is used to assess the mean absorbed dose to normal organs and tissues. The activity distribution is assumed to be uniform and the calculated mean absorbed dose serves as a good representation of the absorbed dose since the volumes are... (More)
Internal dosimetry deals with the assessment of absorbed dose for radionuclides distributed inside the body. The absorbed dose is in its turn used for correlation with the biological effect caused by the irradiation. In radioimmunotherapy is however the correlation not easily found and factors influencing this are evaluated and discussed in this work. The internal dosimetry could be subdivided into three levels; macroscopic, small-scale, and microscopic dosimetry. Macroscopic dosimetry: The MIRD S formalism is used to assess the mean absorbed dose to normal organs and tissues. The activity distribution is assumed to be uniform and the calculated mean absorbed dose serves as a good representation of the absorbed dose since the volumes are large compared to the range of emitted particles. The mean absorbed dose to normal organs and tumours was determined for B-cell lymphoma patients undergoing radioimmunotherapy with 90Y-hLL2 (Paper I). The absorbed dose to bone marrow, which is the most radiation sensitive tissue in the body, could be calculated via a method based on the activity in blood samples. The ratio of the activity concentration in bone marrow to the activity concentration in blood was, however, found not to be constant over time. A method for taking this into account in the calculations was proposed (Paper II). Lymphomas are in general radiation sensitive, fast-responding tumours. A decrease in the mass of a tumour during the course of radioimmunotherapy could have a strong influence on the calculated absorbed dose and a method for correction due to this effect was developed (Paper III).



Small-scale dosimetry: The MIRD formalism is used, but as the volume is smaller, the mean absorbed dose serves as a poorer representation of the absorbed dose. A model of the anatomy of a mouse was developed and the influence on the S values (absorbed dose per decay) for the choice of organ mass, shape of the organs and distances between the organs was investigated (Paper IV). The average number of atoms per tumour cell was determined from blood samples from a patient having a B cell lymphoma. The MIRD cellular S values were used for calculation of the mean absorbed dose to a cell (Paper V).



Internal microdosimetry: The absorbed dose is the expectation value of the specific energy, which is a quantity that takes stochastic effects of the energy depositions into account. The smaller a volume, the larger stochastic effects are seen. Lymphoma patients could have a leukaemic spread of their disease and as 90Y often is used for therapy, the treatment to the single tumour cells is not optimized. Theoretical calculations were performed based on experimental data for an evaluation (Paper VI). (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Professor Stabin, Michael G., Dept. of Radiology and Radiological Sciences, Vanderbuilt University Nashville, TN, USA
organization
publishing date
type
Thesis
publication status
published
subject
keywords
radiobiologi, Nukleärmedicin, radiobiology, Nuclear medicine, B-cell lymphoma, Radioimmunotherapy, Radionuclide therapy, Internal dosimetry, Radiopharmaceutical technology, Radiofarmaceutisk teknik
pages
48 pages
publisher
Cecilia Hindorf, Dept. of Medical Radiation Physics, Lund University Hospital, SE-221 85 Lund, Sweden,
defense location
F3, Blocket, Lund University Hospital
defense date
2004-03-11 10:00
ISBN
91-974444-3-X
language
English
LU publication?
yes
id
3c192150-33cd-40b6-a5f4-31b49bdf32e0 (old id 466705)
date added to LUP
2007-09-07 13:46:52
date last changed
2016-09-19 08:45:13
@misc{3c192150-33cd-40b6-a5f4-31b49bdf32e0,
  abstract     = {Internal dosimetry deals with the assessment of absorbed dose for radionuclides distributed inside the body. The absorbed dose is in its turn used for correlation with the biological effect caused by the irradiation. In radioimmunotherapy is however the correlation not easily found and factors influencing this are evaluated and discussed in this work. The internal dosimetry could be subdivided into three levels; macroscopic, small-scale, and microscopic dosimetry. Macroscopic dosimetry: The MIRD S formalism is used to assess the mean absorbed dose to normal organs and tissues. The activity distribution is assumed to be uniform and the calculated mean absorbed dose serves as a good representation of the absorbed dose since the volumes are large compared to the range of emitted particles. The mean absorbed dose to normal organs and tumours was determined for B-cell lymphoma patients undergoing radioimmunotherapy with 90Y-hLL2 (Paper I). The absorbed dose to bone marrow, which is the most radiation sensitive tissue in the body, could be calculated via a method based on the activity in blood samples. The ratio of the activity concentration in bone marrow to the activity concentration in blood was, however, found not to be constant over time. A method for taking this into account in the calculations was proposed (Paper II). Lymphomas are in general radiation sensitive, fast-responding tumours. A decrease in the mass of a tumour during the course of radioimmunotherapy could have a strong influence on the calculated absorbed dose and a method for correction due to this effect was developed (Paper III).<br/><br>
<br/><br>
Small-scale dosimetry: The MIRD formalism is used, but as the volume is smaller, the mean absorbed dose serves as a poorer representation of the absorbed dose. A model of the anatomy of a mouse was developed and the influence on the S values (absorbed dose per decay) for the choice of organ mass, shape of the organs and distances between the organs was investigated (Paper IV). The average number of atoms per tumour cell was determined from blood samples from a patient having a B cell lymphoma. The MIRD cellular S values were used for calculation of the mean absorbed dose to a cell (Paper V).<br/><br>
<br/><br>
Internal microdosimetry: The absorbed dose is the expectation value of the specific energy, which is a quantity that takes stochastic effects of the energy depositions into account. The smaller a volume, the larger stochastic effects are seen. Lymphoma patients could have a leukaemic spread of their disease and as 90Y often is used for therapy, the treatment to the single tumour cells is not optimized. Theoretical calculations were performed based on experimental data for an evaluation (Paper VI).},
  author       = {Hindorf, Cecilia},
  isbn         = {91-974444-3-X},
  keyword      = {radiobiologi,Nukleärmedicin,radiobiology,Nuclear medicine,B-cell lymphoma,Radioimmunotherapy,Radionuclide therapy,Internal dosimetry,Radiopharmaceutical technology,Radiofarmaceutisk teknik},
  language     = {eng},
  pages        = {48},
  publisher    = {ARRAY(0xa680fc0)},
  title        = {Internal dosimetry. Macroscopic, small-scale and microscopic perspectives},
  year         = {2004},
}