Indium-113m 제제의 조제법과 그의 임상적 응용에 관한 실험적 연구

Abstract

[한글]

Experimental Studies on the Preparations and on Their Clinical Applications of

Indium -ll3m Compounds

Yong Kyu Choe, M.D.

Department of Medical Science The Graduate School, Yonsei University

(Directed by Professor:

Seung Bong Ahn, M.D. and Associate Professor: Byung Sook Choi, M.D.)

1. A Experimental Study on the Preparations ef Indium-ll3m Compounds

Radioactive Indium· 113m, one of the short·lived nuclides, has been introduced

recently into nuclear medicine (Goodwin et al, 1966; Stern et al, 1966; Stern et

al, 1967). There are various compounds for scanning such as**113m In·Chloride for

heart and placenta, 113mIn·iron-macroaggregate for lung, 113mIn·chelate complex

far brain and kidney, and 113mIn·colloid for liver and spleen.

The radioactive Indium· 113m compounds have been prepared by various complicated

methods (Bruno et al, 1968; Potchen et al,1968; Burdine et al, 1969; French, 1969),

but a standard method for preparation has not yet been reported. However, there is

a generally accepted idea that the chemical composition of Indium-113m compounds

depends net only on the solvent which should be added to the indium-l 13m eluate,

but also on the change of the pH level of Indium·113m compounds. This study is

aimed at finding out the optimal pH level of Indium·l13m compounds which fire

prepared by a simplified and standardized method for Indium-113m compounds.

113mIn·chloride, 113mIn-colloidal, 113mIn-iron-macroaggregated, and

113mIn-chelate forms were prepared by changing the pH level by dilute phosphate

buffer (0.04mole, pH 7.8) and sodium hydroxide solution(0.1N).

The Indium-113m compounds prepared at different pH levels were injected

intravenously into rabbits, and the distribution of their radioaotivity in the

internal organs and the blood disappearance rate were assayed.

The experimental results are summarized as follows:

1. The control of the pH level in Indium-113m compounds by phosphate buffer is

easier than by modium hydroxide solution.

2. Depending on the pH level of Indium·113m compounds in phosphate buffer or in

sadium hydroxide solution, the distribution of Indium·113m activity in the

internal organs in significantly different, as follows:

a. Indium·113m compound below pH 4.5 remains in the blood at the highest level

of per gram assessment of organs, and the half time of blood disappearance rate of

Indium· 113m compound in phosphate buffer (pH2.5) is 242.7 minutes and for

midiutes and for hydroxide solution (pH2.5), 183.7 minutes.

b. Of the Indium·113m compound at pH 6.5 in phosphate buffer 75.9% is retained

in the liver and at pH 8.0 in sodium hydroxide solution 2.8% is retained per gram

in the spleen with the highegt organ distribution in per gram assessment.

3. 113mIn-iron-macroaggregated form at PH 9.0 in Sodium hydroxide is useful for

lung scanning with the highest distribution in organs (62.4% of the administered

dose), and ll3mIn-iron-macroaggregated form at pH 3.0 in phosphate buffer is for

the combined scanning of lung and liver.

4. Urinary excretion of ll3mIn·DTPA of pH 6.7∼7.0 in phosphate buffer or in

sodium hydroxide solution is higher than that of pH 2.5∼3.0. The half time of the

blood disappearance rate of ll3mIn-DTPA of pH 6.5∼7.0 in phosphate buffer is

longer than that of sodium hydroxide solution, but the organ distribution of

113mIn·DTPA at pH 6.5∼7.0 in sodium hydroxide solution is higher than that in

phosphate buffer. Therefore, 113mIn-DTPA at PH 6.5∼7.0 in phosphate buffer is

profitable for kidney scanning and 113mIn·DTPA at pH 6.5∼7.0 in sodium hydroxide

solution, for brain scanning.

2. Comparative Studies on Clinical Applications of Indium-ll3m Compounds and the

Other Preparations

Indium-113m compounds have been attracting more general interest as a broad

spectrum agent for organ visualization (Wagner, 1968; Adatepe and Potchen, 1969;

O'mara et al, 1969),

However, there have been few studies of the quantitative functional analysis

using Indium-113m compounds for various organs. This study is aimed at the

comparison of Indium-113m compounds with other preparations in respect to the

quantitative analysis of liver and kidney function, the estimation of blood volume,

and on an analysis of liver scanning.

54 healthy Korean adults, 21 with hepatopathy, 10 with nephropathy and 499 liver

scans which included 381 scans using ll3mIn colloid and 118 scans using 198Au

colloid were examined and evaluated by the following methods:

1. The external counting for the half title of liver uptake and blood

disappearance were carried out over the liver and the left lateral side of the head

following ll3mIn colloid injection as a liver function test. The external counting

was corrected by the ll3mIn decay factor and analysed by the measuring method of

colloidal disappearance rate of the blood (Dobson and Jones, 1952 : Vetter et al,

1954). This also has done using 198Au colloid without correction of decay factor on

the following day on the same subjects.

2. The glomerular filtration rate (G.F.R.) was detected by the usual external

counting method at the cardiac area and the blood sample which nuts taken at 20

minutes after injection of 1193mIn-DTPA in phosphate buffer.

G.F.R. was calculated by plasma activity of Indium-113m obtained from the blood

sample and a half time of blood disappearance obtained from the external counting

(Wagner, 1968).

3. The renogram was performed by the usual conventional technique. The

ll3mIn-DTPA in sodium hydroxide solution was injected and 131I-hippuran, the next

day. The renograms were evaluated by Krueger's quantitative analysis.

4. The plasma and blood volume were estimated by 113In chloride, and they ware

compared with 125I-HSA on the following day.

5. The liver scans using ll3mIn colloid (212 abnormal and 169 normal cases) and

198Au colloid (118abnormal cases) were analysed with the findings of mottled

densities of the liver, perihilar accumulation of activity and extrahepatic organ

visualization.

The results are summarized as follows:

1. Correlation of the half time between liver uptake and blood disappearance rate

of ll3mIn colloid, and of the half times of liver uptake and blood disappearance

rate between 198Au colloid and ll3In colloid are indicated as significant values

(Correlation coefficiency, r=0.78, 0.87 and 0.78).

2. ll3mIn-DTPA for the glomerular filtration rate is a very simplified method,

and the G.F.R. is similar to that of the inulin method (110.4±10.8ml/min./1.73㎡

in adult by ll3mIn-DTPA).

3. The pattern of the renogram using ll3mIn-DTPA consists of 3 components as

shown by 131I-hippuran, and the quantitative analyses of the renograms of

113mIn·DTPA (total concentration, minute concentration, and minute excretion by

Krueger's method) are little lower than that ot 131I-hippuran.

4. ll3mIn chloride in phosphate buffer can be used for the measurement of blood

and plasma volume, and the plasma volume by ll3mIn chloride is ±6.4% in comparison

to that obtained by 125I·HSA.

5. Indium-113m colloid in contrast to 198Au colloid has the advantage of

delineating a large space occupying lesion in a liver scan, whill the small diffuse

liver abnormality such as a mild degree of cirrhosis or hepatitis is poorly

identified.

[영문]

1. A Experimental Study on the Preparations ef Indium-ll3m Compounds

Radioactive Indium· 113m, one of the short·lived nuclides, has been introduced recently into nuclear medicine (Goodwin et al, 1966; Stern et al, 1966; Stern et al, 1967). There are various compounds for scanning such as**113m In·Chloride for

heart and placenta, 113mIn·iron-macroaggregate for lung, 113mIn·chelate complex far brain and kidney, and 113mIn·colloid for liver and spleen.

The radioactive Indium· 113m compounds have been prepared by various complicated methods (Bruno et al, 1968; Potchen et al,1968; Burdine et al, 1969; French, 1969), but a standard method for preparation has not yet been reported. However, there is a generally accepted idea that the chemical composition of Indium-113m compounds depends net only on the solvent which should be added to the indium-l 13m eluate, but also on the change of the pH level of Indium·113m compounds. This study is aimed at finding out the optimal pH level of Indium·l13m compounds which fire prepared by a simplified and standardized method for Indium-113m compounds.

113mIn·chloride, 113mIn-colloidal, 113mIn-iron-macroaggregated, and 113mIn-chelate forms were prepared by changing the pH level by dilute phosphate buffer (0.04mole, pH 7.8) and sodium hydroxide solution(0.1N).

The Indium-113m compounds prepared at different pH levels were injected intravenously into rabbits, and the distribution of their radioaotivity in the internal organs and the blood disappearance rate were assayed.

The experimental results are summarized as follows:

1. The control of the pH level in Indium-113m compounds by phosphate buffer is easier than by modium hydroxide solution.

2. Depending on the pH level of Indium·113m compounds in phosphate buffer or in sadium hydroxide solution, the distribution of Indium·113m activity in the internal organs in significantly different, as follows:

a. Indium·113m compound below pH 4.5 remains in the blood at the highest level of per gram assessment of organs, and the half time of blood disappearance rate of Indium· 113m compound in phosphate buffer (pH2.5) is 242.7 minutes and for midiutes and for hydroxide solution (pH2.5), 183.7 minutes.

b. Of the Indium·113m compound at pH 6.5 in phosphate buffer 75.9% is retained in the liver and at pH 8.0 in sodium hydroxide solution 2.8% is retained per gram in the spleen with the highegt organ distribution in per gram assessment.

3. 113mIn-iron-macroaggregated form at PH 9.0 in Sodium hydroxide is useful for lung scanning with the highest distribution in organs (62.4% of the administered dose), and ll3mIn-iron-macroaggregated form at pH 3.0 in phosphate buffer is for the combined scanning of lung and liver.

4. Urinary excretion of ll3mIn·DTPA of pH 6.7∼7.0 in phosphate buffer or in sodium hydroxide solution is higher than that of pH 2.5∼3.0. The half time of the blood disappearance rate of ll3mIn-DTPA of pH 6.5∼7.0 in phosphate buffer is longer than that of sodium hydroxide solution, but the organ distribution of 113mIn·DTPA at pH 6.5∼7.0 in sodium hydroxide solution is higher than that in phosphate buffer. Therefore, 113mIn-DTPA at PH 6.5∼7.0 in phosphate buffer is profitable for kidney scanning and 113mIn·DTPA at pH 6.5∼7.0 in sodium hydroxide solution, for brain scanning.

2. Comparative Studies on Clinical Applications of Indium-ll3m Compounds and the Other Preparations

Indium-113m compounds have been attracting more general interest as a broad spectrum agent for organ visualization (Wagner, 1968; Adatepe and Potchen, 1969; O'mara et al, 1969),

However, there have been few studies of the quantitative functional analysis using Indium-113m compounds for various organs. This study is aimed at the comparison of Indium-113m compounds with other preparations in respect to the quantitative analysis of liver and kidney function, the estimation of blood volume, and on an analysis of liver scanning.

54 healthy Korean adults, 21 with hepatopathy, 10 with nephropathy and 499 liver scans which included 381 scans using ll3mIn colloid and 118 scans using 198Au colloid were examined and evaluated by the following methods:

1. The external counting for the half title of liver uptake and blood disappearance were carried out over the liver and the left lateral side of the head following ll3mIn colloid injection as a liver function test. The external counting was corrected by the ll3mIn decay factor and analysed by the measuring method of

colloidal disappearance rate of the blood (Dobson and Jones, 1952 : Vetter et al, 1954). This also has done using 198Au colloid without correction of decay factor on the following day on the same subjects.

2. The glomerular filtration rate (G.F.R.) was detected by the usual external counting method at the cardiac area and the blood sample which nuts taken at 20 minutes after injection of 1193mIn-DTPA in phosphate buffer.

G.F.R. was calculated by plasma activity of Indium-113m obtained from the blood sample and a half time of blood disappearance obtained from the external counting (Wagner, 1968).

3. The renogram was performed by the usual conventional technique. The ll3mIn-DTPA in sodium hydroxide solution was injected and 131I-hippuran, the next day. The renograms were evaluated by Krueger's quantitative analysis.

4. The plasma and blood volume were estimated by 113In chloride, and they ware compared with 125I-HSA on the following day.

5. The liver scans using ll3mIn colloid (212 abnormal and 169 normal cases) and 198Au colloid (118abnormal cases) were analysed with the findings of mottled densities of the liver, perihilar accumulation of activity and extrahepatic organ visualization.

The results are summarized as follows:

1. Correlation of the half time between liver uptake and blood disappearance rate of ll3mIn colloid, and of the half times of liver uptake and blood disappearance rate between 198Au colloid and ll3In colloid are indicated as significant values (Correlation coefficiency, r=0.78, 0.87 and 0.78).

2. ll3mIn-DTPA for the glomerular filtration rate is a very simplified method, and the G.F.R. is similar to that of the inulin method (110.4±10.8ml/min./1.73㎡ in adult by ll3mIn-DTPA).

3. The pattern of the renogram using ll3mIn-DTPA consists of 3 components as shown by 131I-hippuran, and the quantitative analyses of the renograms of 113mIn·DTPA (total concentration, minute concentration, and minute excretion by Krueger's method) are little lower than that ot 131I-hippuran.

4. ll3mIn chloride in phosphate buffer can be used for the measurement of blood and plasma volume, and the plasma volume by ll3mIn chloride is ±6.4% in comparison to that obtained by 125I·HSA.

5. Indium-113m colloid in contrast to 198Au colloid has the advantage of delineating a large space occupying lesion in a liver scan, whill the small diffuse liver abnormality such as a mild degree of cirrhosis or hepatitis is poorly identified.