99mTc Master Milker(TcMM)

Generator of highly concentrated pure 99mTc fromlow specific activity 99Mo produced by reactor
and/or electron linear accelerator

Based on a newly discovered phenomenon!!

Ø A general activated carbon has the peculiar characteristics tobe able to collect 99mTc preferentially and completely fromhighly concentrated LSA-Mo(99Mo) solution.

Kaken 99Mo-99mTc Process@for Globally Local 99Mo-99mTc production
on demand by combination with TcMM andneighboring reactor or LinacKaken Inc., JapanContact to tatenuma@kakenlabo.co.jp http://www.kakenlabo.co.jp99Mo 2016 Topical Meeting

99mTc Master Milker (TcMM)

Generator of highly concentrated pure 99mTc
from low specific activity 99Mo produced byreactor and/or electron linear accelerator
OUTLINE

Extraction technique of 99mTc extraction from 99Mo was examined by the newly developed Technetium
Master Milker (TcMM) method. For the production of 99Mo here, the 98Mo(n,g) reaction using neutrons
generated by a nuclear reactor and/or the 100Mo(g,n) reaction using bremsstrahlung photons generated byan electron linear accelerator were utilized respectively. 	
By this study, it has been proved that a highly concentrated pure pertechnetate (99mTcO4-) in saline canbe separated and collected through the TcMM method. 	
Procedurally, the TcMM method utilizes combined activated carbon (AC) and alumina (AL), with orwithout ion exchange resin (IER). The AC-AL process has used a highly concentrated Mo with low specificand large activity 99Mo of 3.0x1012 Bq generated by the irradiation of neutrons in the nuclear reactor, JRR-3in Japan Atomic Energy Agency. 	
It was found that a chemical yield and purity of the produced 99mTc are 90-95% and 6N (99.9999 %),respectively. Therefore, the TcMM method is able to generate a high quality 99mTcO4- that is eligible toobtain the permission of pharmaceutical affairs law.	
It is revealed that the TcMM method has the practical capability of the efficient 99mTc generator with awide range from small amount level (kBq) to large level (TBq) per batch, furthermore, the main parts
consisted of the AC-AL or AC-IER-AL columns system are simple and are able to collect pure 99mTc within
30 min automatically.	
Conclusively, 99mTc can be produced domestically and further locally on demand by the combination of theTcMM method and 99Mo with a low specific activity (produced from the 98Mo(n,g) and/or 100Mo(g,n)
reaction, using a neighboring reactor and/or an electron linear accelerator without enriched uranium (HEUand LEU)), and furthermore, the advanced use for diagnosis can be available everywhere in the world.	
Step(2) Mo(99Mo) flow

[TcMM Process]Step(1) Dissolutionof irradiated natMoO3 pellets	
nat99mTc

Irradiated MoO3 pellets are dissolved in a molar equivalentNaOH solution, and the resulting Na2Mo(99Mo)O4 solution withthe neutral pH can obtain.

99Mo

Step(3) H2O rinse
Step(3) NaOH rinse

99Mo

Step(4) 99mTc elution by H2O
Step(5) Na+ removal by IER99Mo99Mo sol.
99Mo

Step(1)
Mo sol.

99mTc

99mTc

AC

99mTc complete adsorption
99mTc

99Mo

Mo(99Mo) not adsorption

Step(2) Adsorption of 99mTc99 in AC 	

Using the TcMM system, Na2Mo( Mo)O4 solution (max. 1000mL) is poured into AC column at a flow velocity of 100 mL/min
for 10 min. to adsorb 99mTc on the AC column. A trace amount
99mTc is preferentially and completely adsorbed in the ACcolumn.

NaNa+ removal

IER

waste

TcMM Process	Na	

Step(6) SalineStep(3)
Removal of Mo contaminants from AC	
9999mTc

ALMo( Mo) and other nuclides contaminants in AC is removed byflowing H2O, next 6.0 M NaOH (30 mL) and finally H2O.	

99mTc

99mTc adsorption& purification

99mTc

wasteStep(4) Elution of 99mTc from AC

In order to elute 99mTc collected into AC column, H2O is run
through the AC column, then the whole quantity of 99mTc
adsorbed on AC column can be eluted.	

Step(5) Removal of Na-ion in alkaline
eluted	99m

Finally, a highly pure 99mTc can be recovered from the AL
column by flowing 10-20 mL of saline (0.9% NaCl solution), andthe resulting 99mTc can be concentrated 50-100 folds from theinitial Mo (99Mo) solution.

99mTc

diagnosis

TcMM type(TcMM process)

TcMM 10T(AC-AL)TcMM<IER> 10T(AC-IER-AL)

amounts of 99Mo

kBq-10TBq

kBq-10TBq

Mo solution

200g(Mo)/L200g(Mo)/LAC column

LH2c-AC 4.5g,
Flow rate of Mo sol.
100mL/min
6M-NaOH 30mL
99mTc elute H O 85mL
2LH2c-AC 4.5g,
Flow rate of Mo sol.
100mL/min
6M-NaOH 30mL
99mTc elute H O 85mL
2IER column-----DIAION(SK1B H) 5cc

AL column

MP-acid AL 12g
Saline 20mL

MP-acid AL 6.0g
Saline <10mL

99mTc milking time

≤30min≤30minvolumeconcentration rate
radiochemical purity

20mL
50 folds>99.99%≤10mL	
00 folds or more
>99.99%wastes per batch

Liquid: 250 mL
Solid: 17g

Liquid: 250 mL
Solid: 16g

99mTc

Tc solution obtained in step(4) above is alkaline solution isflowed through to the strong acid type of ion exchange resin(IER) and the activated alumina (AL). By this procedure, Na-ion
in eluted 99mTc solution can be taken hold in the IER column and
99mTc can be caught in the AL column. 	
If the IER column is not used, the TcMM process can also beoperated by the combination of AC-AL columns system.	

Step(6) Elution of 99mTc	

TcMM conditions	

99mTc collectedKaken Inc. URL : http//www.kakenlabo.co.jp 		rradiated Mo(99Mo)O3�
! Dissolution by NaOH�

	
rradiated Mo(99Mo)O3�

Mo(99Mo+99mTc) stock solution! Dissolution by NaOH�
pH neutral�

99mTc adsorption

recovery& reuse

99mTc adsorption& elution�

Alkali removal�

99Mo sol.

waste

Alkali removal &99mTc purification�
AL column(12g)ØBy the labeling experiment using many kits,
the target medicines are given with high radiochemical purity.	

99mTc purification�

AL column
(6g)

rinse
waste
99mTc sol.

(a) AC-AL Process(b) AC-IER-AL Process

Sufficient performance for 99mTc
generator!!

TcMM Process	Ø Complete removing impurities such as
accumulated 99gTc, generated radioactive
Nb and other nuclides contaminants.
Ø Highly pure 99mTc (radiochemical purity:>99.99%) is successfully separated with achemical yield of 90% over.
Ø TcMM enables one to generate a highquality 99mTcO4- (pertechnetate) available
for obtaining permission ofpharmaceutical affairs law.
Ø By using the TcMM system, a highly
concentrated pure 99mTc of kBq-TBq froma low specific activity 99Mo canautomatically be collected in a short time(<30min.).
Ø TcMM can also be utilized just a 99mTc
High purity
Reactorconcentrator.
Highrecovery�

TcMM can,in the near future, where thesystem usinga neighboring reactor, aL I N A C a n d t h e 9 9 m Tc separation system of the TcMM
are available in an appropriate
KURRI-LINACの概要
number of clinics andhospitals in each area.	
99Mo-production-->

TcMM-10T
Front panel(max. 10TBq)�

<KURRI-LINACとは>

Irradiation capsule�

京都大学原子炉実験所の電子線型加速器（電子ライナック）は1965年（昭和40年）に、パルス状中性子を発生させるための中性子発生装置として熊取キャンパスに設置されました。KURRILINACの名称は、Kyoto University, Research Reactor Institute - Linear Acceleratorからきています。
２本の進行波型加速管を持つライナックで加速されたパルス状の電子ビームを、タンタルやタングステンなどの重金属ターゲットに照射することにより、パルス状の中性子を得ることができます。そのため、研究炉での定常中性子を使った研究に対し、対照的かつ相補的な研究を行うことができます。また、電子線やＸ線による材料照射のほか、最近では短バンチ電子ビームに由来したコヒーレント放射光の発生研究や、それを用いた遠赤外・ミリ波領域での分光研究も行われています。この電子ライナックは、実験所の他の施設（研究炉、臨界集合体、コバルト60ガンマ線照射装置）と並び全国共同利用施設になっており、全国の研究者に利用されています。

MoO3 pellet�Φ20mmx10mmt	

Irradiation
by Linacor Reactor�

1.E+15120

Radiochemical+purity+of+99mTc+
4N7+100<ページの先頭へ>[Detected NUclides] 99Mo(99mTc)
90Nb, 91mNb, 92mNb, 95Nb, 95mNb, 96Nb

Linac
100Mo(γ,n)99Mo�
Linac-(γ,n) Mo

98Mo(n,γ)99Mo�

JRR-3
Recovery rate of 99mTc [%]KUR-Linac	ØLiquid waste: 250mL/runØSolid waste: AC 4.5g/run, AL 6~12g/run,
IER 5cc/run, and column casing

Waste forproduction	

99mTc sol.

KURRI-LINACとは電子線型加速器とはKURRI-LINACの性能・仕様
中性子発生装置棟（ライナック棟）の概観
KURRI-LINACのスタッフØEndotoxin-inspection: negativeØRadiochemical purity: >4N~7N

Quality of99mTc	

IER column(5cc)

SalinerinseØ99mTc collected in sterile salineØCollected as 99mTcO4- (pertechnetate)

SalinerinseAC column(4.5g)

ØConcentration of 99mTc solution: >1Ci/mLØProducing time: ≤30 min/runAC column(4.5g)

99Mo sol.

& elution�

Producingprocess of99mTc	

6N1+

6N8+

7N7+

7N5+

7N4+

7N2+

7N2+

7N5+

7N4+

1.E+14
1.E+1380

1.E+1260
1.E+1140■ Recovery rate of 99mTc [%]● Activity of 99Mo [Bq]20

 Activity of recovered 99mTc [Bq]

1.E+10
1.E+09Activity of 99Mo, 99mTc [Bq]

6M-NaOH
H 2OrinseØEquivalent 99mTc recovery rate in kBq-10TBq
ØRecovery of 99mTc : 90~95%

pH neutral�

6M-NaOHH 2OMo(99Mo+99mTc) stock solution

recovery& reuse

Performance of TcMM process for generating 99mTc
from (γ,n) & (n,γ) LSA-99Mo	

991.E+08

00

natMoO pellet Irradiated
31

2

3

4by Linac

567

8

910

11

Milking number

Detected nuclides
99Mo, 99mTc,187W, 92mNb, 24Na,198Au, 134Cs, 124Sb, 60Co, 86Rb

Detected nuclides
99mTc

1.7-1.8e+12 Bq
99mTc 1.7-1.8e+12 Bq

Nuclides generated in
Linac-irradiation natMoO3

1.80E+06

25MeV

1.60E+06

Bq/g(pellet)

TcMM process

30MeV

1.40E+06[main nuclear reactions]
97Mo(γ,p)96Nb
96Mo(γ,p)95mNb&95Nb
94Mo(γ,pn)92mNb
92Mo(γ,p)91mNb
92Mo(γ,pn)90mNb

purity: 7N7

99Mo

2.00E+06

35MeV

1.20E+06

99Mo

99mTc

ND <5e+4 Bq
1.6-1.7e+12 Bq

99mTc purity

1.00E+06>4N-7N�

8.00E+05
6.00E+05
4.00E+05
2.00E+05
0.00E+00

Nb- 95m Mo- 99

Nb- 95

Nb- 96

Nb- 92m Nb- 90

NuclidesNb- 91m

Linac-(γ,n)99Mo and impurity nuclides generated	a) Mo(99Mo) solutionb) Collected 99mTc

γ-spectra of (n,γ)99Mo and 99mTc collected by TcMM process	

Contact to : tatenuma@kakenlabo.co.jp 	

99Mo 2016 Topical Meeting

Kaken 99Mo-99mTc Process@99Mo-99mTc Domestic & Local Production on demand
99Mo production [Reactor or Accelerator]
99Mo

Natural or Enriched isotope MoO3 or Mo[by Reactor] 98Mo(n,γ)99Mo[by Linac] 100Mo(γ,n)99Mo

Low Specific Activity 99Mo
LSA-99Mo 0.1-1Ci/g(Mo)LSA-99Mo
99mTc Master Milker [TcMM]
99mTc

Patented

Concentration & purification of 99mTc
by activated carbon(AC) & alumina(AL)! 99mTc milking performance:
Bq-10TBq within 30min.
! Mo(	9Mo) specific activity andconcentration: without restriction.
! 99mTc purity in saline: >6N! milked 99mTc concentration:
kBq-TBq/mL! 99mTc chemical form: TcO4-

Small AC-(IER)-AL
kBq-10GBq

TcMM
GBq-10TBq

99mTc generator

AC-(IER)-AL
99mTc pharmaceuticalKaken 99Mo-99mTc Process@	used Be pebble

Tritium(3H)/Li/Be

Resource Recycle System fornuclear fusionNeutron	  Multiplier	  bed	  layer	  Breeder	   bed	  layer(Li2TiO3	  or	  Li2O)

ITER
ITER	

Chlorination	  Dry	  method

used Li-ceramics pebble
dissolution

Be resource recycle

removal	  of	  impurities

removal	  of	  impurities
3H	  &	  60Co

Li resource recycle
Li	  isotope	  separation	  &	  concentrationenriched	  6Licontrol	  of	  6Li	  content	  &	  Li/Ti	  ratio

Outline of Kaken tasks

Tritium
recyclerecovery	  BeCl2-­‐-­‐>Be

recovery	  purified	  Be	  powder
reproduction	  of	  Li-­‐ceramics	  pebble

Chemical and Instrumental Analysis
Environmental analysis
Physical analysis
Pd-­‐Pt	  chromato.
Be	  &	  Beryllide
Li reuse
refined	  Li-­‐ceramics	  pebble
Ultra-trace analysis
Pebble	  fabrication
BlanketTritium	  separation	  &	  recovery
Inorganic and Organic analysis
reproduction	  of	  Be	  &	  Beryllide pebble
Chemical Experiment and R&D support
Be reuse
Chemical process development
Material test and evaluation
refined	  Be	  pebble
Functional material development
Radionuclides-related research and analysis
Radioactivity analysis on environmental samples/Transitional surveys
Test and technology based on radioisotopes
Technology development with application of radioactive substancesRadioactive waste reprocessing
Engineering Design and Manufacture
Design & fabrication of original devices and equipment
(拡大)

100µm

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