Radiochemistry of Technetium-99m Otto C. Boerman, PhD Radboud University Nijmegen Medical Center, The Netherlands
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Radiochemistry of Technetium-99m
Otto C. Boerman, PhD
Radboud University Nijmegen Medical Center, The Netherlands
Radboud University Nijmegen Medical Center, The Netherlands
Radboud University Nijmegen Medical Center, The Netherlands
Radboud University Nijmegen Medical Center, The Netherlands
TechnetiumTechnetium
- 1850: Dimitri Mendeleev: Em- 1846-1908: Ilmenium, Pelopium, Davyum, Nipponium- 1925: Noddack et al.: Masurium- 1937: Perrier & Segre: Panormium τεχνητοζ1937: Perrier & Segre: Panormium, τεχνητοζ
- Oxidation state: 0, 1+, 2+, 4+, 5+, 6+, 7+
5
- 1962: Kenna & Kuroda - pitchblende Congo: 0.2 ng/kg
Technetium-99mTechnetium 99m
• 99mT i t t bl t t f t h ti 99 (99T ) ith• 99mTc is a metastable state of technetium-99 (99Tc) witha half-life of 6.02 hours.
• decay to the ground state of 99Tc: 90% emission ofdecay to the ground state of Tc: 90% emission ofgamma photons of 140 keV
Mo-99
T 99Tc-99m
6
Tc-99
Radiation exposure from Tc 99mRadiation exposure from Tc-99m
• The specific gamma ray constant for Tc-99m is 2 mGy / hour.MBq at 1 cm
• The half-value layer is 0.17 mm lead • C t l f th di ti• Control of the radiation exposure:
reduction factor
0.5 0.1 0.01 0.001 0.0001factormm Pb 0.17 0.8 1.6 2.5 3.3
7
Production of Technetium 99mProduction of Technetium-99m
8
Development of Tc 99m generator at BNLDevelopment of Tc-99m generator at BNL
Powell "Jim" Richards and Walter Tucker
9
Powell Jim Richards and Walter Tucker
Tc-99m generatorTc 99m generator
- Technetium 99m (99mTc) is a decay product of molybdenum-99 (t½ = 66 h)Obt i d b l ti it f l bd 99 t
10
- Obtained by eluting it from a molybdenum-99 generator
Labeling halfproducts with Tc 99mLabeling halfproducts with Tc-99m
• Reduction of TcO4-
• Reductor: Sn2+, Fe2+ TcO4-
• Incubation with halfproduct• Quality control
• Radionuclidic purity: breakthrough of Mo-99740 k V h t 0 5 l d d lib t740 keV photons, 0.5 cm lead, dose calibrator
• ITLC: stationary phase silicagel
TcO2
• ITLC: stationary phase – silicagelmobile phase – 0.1 M ammonium acetate, pH 5.5
Coordination chemistry of Tc 99mCoordination chemistry of Tc-99m
TcO4-
Sn2+
Tc(V)
Square pyrimidal complex
12
Gluconate glucoheptonate
Tc-99m-labeled agents for myocardial perfusionTc 99m labeled agents for myocardial perfusion
99mTc-sestamibi
13
Tc-99m-labeled agents for cerebral perfusionTc 99m labeled agents for cerebral perfusion
14
Tc 99m labeled agents for renal functionTc-99m-labeled agents for renal function
15
Tc 99m demotateTc-99m-demotate
16
Tc-99m-Methylene diphosphonate (MDP)Tc 99m Methylene diphosphonate (MDP)
17
Labeling antibodies peptides and small molecules with Tc 99mLabeling antibodies, peptides and small molecules with Tc-99m
Direct labeling method:
Using free sulfhydril groups of the biomolecule to chelate Tc-99m
(Schwarz method, iminothiolane method)
Bifunctional chelate method:Bifunctional chelate method:
Modification of biomolecule with bifunctional chelating agent
(HYNIC, MAG3, tetraamine, a.o.)
Hybrid method:
Incorporating tripeptide sequence (Gly3, Cys-Gly-Gly, Cys-Gly-Cys) to introduce a
N4, N3S, N2S2 donor set
18
Schwarz method: a direct labeling methodSchwarz method: a direct labeling method
• Incubate Ab with β-ME (1000:1)
30 i RT30 min, RT
• Purify Ab by Gelfiltration
• Add transchelator
(gluconate, MDP, tricine)
• Add TcO4-
• Incubate 10 min, RT
• QC with ITLC
M th & Elli J N l M d 1990 31 692 697
19
Mather & Ellison. J Nucl Med 1990; 31: 692-697
Iminothiolane method: a direct labeling methodIminothiolane method: a direct labeling method
protein protein
Patricio et al Q J Nucl Med 1995; 39: 74-75
20
Patricio et al. Q J Nucl Med 1995; 39: 74-75
Tc 99m labeling via a bifunctional chelate: S MAG3Tc-99m labeling via a bifunctional chelate: S-MAG3
H2N-peptide +0.1 M NaHCO3pH 8.5
Hpeptide-N
TcO4-
RTTricine/tartrate
99TcH
Hnatowich et al J Nucl Med 1998; 39: 56-64 Hpeptide-N
21
Hnatowich et al. J Nucl Med. 1998; 39: 56-64 pep de N
Tc-99m labeling via a bifunctional chelate: S-HYNICg
H2N-peptide + peptide-NH
TcO4-
SnCl2Coligand L
peptide
Tc-99m-Interleukin-8
I t l ki 8Interleukin-8
Tc-99m-Interleukin-8
Interleukin-8
8 h4 h2 h1 h1 min
Tc 99m labeling via HYNIC using different coligandsTc-99m labeling via HYNIC using different coligands
25
Rennen et al. Bioconj Chem. 2002; 13: 370
99mTc-IL-8: Effect of the coligandTc IL 8: Effect of the coligand
Tricine EDDA TPPTS Nicotinic Isonicotinic
Abscess/background ratio:
15 23 4 22 29
The coordination of Tc 99m in HYNIC conjugatesThe coordination of Tc-99m in HYNIC-conjugates
27
King et al. Dalton Trans. 2007; 43:4998-5007.
Tc 99m labeling using the hybrid methodTc-99m labeling using the hybrid method
P483: Ac-Lys-Lys-Lys-Lys-Lys-Cys-Gly-Cys-Gly-Gly-Pro-Leu-Tyr-Lys-Lys-Ile-Ile-Lys-Lys-Leu-Leu-Glu-Ser
Incubate peptide with TcO4- glucoheptonate
0.9% NaCl, 20 min, 95 °C0.9% NaCl, 20 min, 95 C
28
Tc 99m labeling using the hybrid methodTc-99m labeling using the hybrid method
P829: cyclo-(N-Me)Phe-Tyr-D-Trp-Lys-Val-Hcy(CH2CO-β-Dap)-Lys-Cys-Lys-NH2
Incubate peptide with TcO4- glucoheptonate
0.9% NaCl, 20 min, RT
29
Tc 99m labeling using the tricarbonyl methodTc-99m labeling using the tricarbonyl method
Formation of Tc(CO)3(H2O)3 complexLabeling of (modified) peptide with the Tc(CO)3(H2O)3 complex
30
- Alberto, Schibli, Egli, Schubiger. PSI Villigen, ETH Zurich
31
Waibel et al. Nat Biotechnol. 1999 ;17:897-901
Tc-99m labeling using the tricarbonyl methodTc-99m labeling using the tricarbonyl method
Synthesis of 99mTc(CO)3(H2O)3+
Reduce TcO4- with NaBH4 and CO (1 atm), 30 min at 75 °CReduce TcO4 with NaBH4 and CO (1 atm), 30 min at 75 C
or using with Isolink™ kit: K2[H3BCO2], 30 min at 100 °C
32
Tc 99m labeling using the tricarbonyl methodTc-99m labeling using the tricarbonyl method
33
Tc-99m labeling using the tricarbonyl methodTc 99m labeling using the tricarbonyl method
• Label (modified) peptide with Tc(CO)3(H2O)3+ at 2 mg/ml
• Mix 1 : 2 with 0.5 M MES, pH 6.2
• Add 99mTc(CO) (H O) +Add 99mTc(CO)3(H2O)3
• Incubate 15-30 min at 37 °C
• Labeling efficiency: 70-95 %
• Purify the labeled peptide
34
99mTc IL 8 in rabbits with i m E Coli infection99mTc-IL-8 in rabbits with i.m. E.Coli infection
99mTc-HYNIC-IL-8 99mTc(CO)3-IL-8
Related Documents
