two-vial kits for the preparation of ren … b mallia radiopharmaceuticals division, radiochemistry...
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Madhava B MalliaRadiopharmaceuticals Division, Radiochemistry and Isotope Group
Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, INDIAE-mail: madhavmb@gmail.com
TWO-VIAL KITS FOR THE PREPARATION
OF 188ReN-DEDC/LIPIODOL FOR THERAPY
OF HCC: INDIAN STORY
THERAPY OF HCC BY TARE: AVAILABLE OPTIONS
Image courtesy: google images
Microspheres(90Y-microspheres such as SIR-Sheres®)
In-situ formed Microdroplets(188Re-Lipiodol or 131I-Lipiodol)
Image courtesy: Yì-Xiáng J. Wáng et al., Chinese Journal of Cancer Research, Vol 27, No 2, 2015.
Microdroplets
90Y- Microspheres 188Re-Lipiodol 131I-Lipiodol
Half-life 64.1 h 16.9 h 8 days
Isotope energy 2.28 MeV (99.9 %) 2.12 MeV (71.4 %)1.96 MeV (25.3 %)
0.60 MeV (71.4 %)0.33 MeV (25.3 %)
Beta range (tissue)(Max – Min)
11.9 - 2.5 mm 11.0 - 2.4 mm 0.3 – 2.0 mm
Imagable gamma No Yes Yes
Production Reactor Generator Reactor
Cost of therapy Very high Moderate to low Moderate to low
188Re Poor man’s Yttrium
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Cancer patient population
Cancer patient population
High Income
Low Income
90Y- SIR-Spheres® 188Re-Lipiodol
COST FACTOR
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188Re-HDD/Lipiodol
• Lee YS, Jeong JM, et al. Nucl Med Commun. 2002; 23(3):237-42.
• Paeng JC, Jeong JM, et al. J Nucl Med. 2003 Dec;44(12):2033-8.
ReN kit DEDC kit
188ReN-DEDC/Lipiodol
• Boschi A, Uccelli L et al. Nucl Med Commun. 2004;25(7):691-9.
188Re-SSS/Lipiodol
• Nicolas Lepareur et al., International Journal of Molecular Imaging, doi:10.1155/2012/278306
Options
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188Re-Radiopharmaceuticals for TARE: General strategy
1. Prepare a lipophilic 188Re-complex
2. Extract into lipiodol
3. Use it for TARE
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188ReN-DEDC complex(DEDC – Diethyl dithiocarbamate)
188ReN-DEDC complex
188ReN intermediate
Step 1
+
DEDC ligand
Step 2
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Step 2Step 1
Glacial acetic acid (150 L)+
Na188ReO4 (up to 3 mL)
KIT 1Incubate for 30 min at room temperature
2 mL saline
KIT 2
1.5 mL of reconstituted solution from kit vial 2
KIT 1
80C, 20 min
KIT 1
3 mL lipiodol
KIT 1
1. Vortex (10 min)2. Centrifuge (10 min)3. Separate lipiodol layer
Step 3
Preparation of 188ReN-DEDC/Lipiodol
Average time for preparation: ~ 60 min
Making the kit more user friendly...
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Step 1
Glacial acetic acid (150 L)+
Na188ReO4 (up to 3 mL)
Incubate for 30 min at
room temperature
KIT 1
Original method
DTCz 2 mg
SnCl2.2H2O 0.8 mg
Sodium oxalate 28 mg
DTCz 2 mg
SnCl2.2H2O 0.8 mg
Sodium oxalate 28 mg
Oxalic acid xx mg
Step 1
Modified method
KIT 1
Na188ReO4 (up to 3 mL)
Incubate for 5 min at
room temperature
pH 3 to 4
pH 3 to 4
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188ReN core
188ReO4-
188ReN core
Kinetics of formation of [188ReN]2+
HPLC of [188ReN]2+ intermediate prepared using oxalate buffer kit
HPLC of [188ReN]2+ intermediate prepared by conventional method
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Step 2
2 mL saline
KIT 2
1.5 mL of reconstituted solution from kit vial 2
KIT 1
80C, 20 min
KIT 1
3 mL lipiodol
KIT 1
1. Vortex (10 min)2. Centrifuge (10 min)3. Separate lipiodol layer
Step 3
Average time for preparation: ~ 35 min
Save 25 mins!!
188ReN-DEDC complex: Prepared by conventional kit using glacial acetic acid
188ReN-DEDC complex: Prepared by oxalate buffer kit
Acknowledgment...• Dr. A. Dash, Head, Radiopharmaceuticals Division, BARC, Mumbai
• Dr. Sharmila Banerjee, Head, Radiation Medicine Centre, Mumbai
• Dr. M. R. A. Pillai, Former Head, Radiopharmaceuticals Division, BARC, Mumbai
• Prof. Adriano Duatti, University of Ferrara, Italy
• Dr. Suresh Subramanian, Radiopharmaceuticals Division, BARC, Mumbai
• Shri. Viju Chirayil, Radiopharmaceuticals Division, BARC, Mumbai
• Sri. Radhakrishnan E R, KMCH, Coimbatore
Our Collaborators• Dr. Ajit Shinto, KMCH, Coimbatore
• Dr. V. Rangarajan, TMH, Mumbai
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