two-vial kits for the preparation of ren … b mallia radiopharmaceuticals division, radiochemistry...

Madhava B MalliaRadiopharmaceuticals Division, Radiochemistry and Isotope Group

Bhabha Atomic Research Centre, Trombay, Mumbai - 400 085, INDIAE-mail: [email protected]

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

3World Rhenium Congress, 2017

Cancer patient population

Cancer patient population

High Income

Low Income

90Y- SIR-Spheres® 188Re-Lipiodol

COST FACTOR


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


World Rhenium Congress, 2017 6

188Re-Radiopharmaceuticals for TARE: General strategy

1. Prepare a lipophilic 188Re-complex

2. Extract into lipiodol

3. Use it for TARE


188ReN-DEDC complex(DEDC – Diethyl dithiocarbamate)

188ReN-DEDC complex

188ReN intermediate

Step 1

+

DEDC ligand

Step 2


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

Typical clinical image...


Making the kit more user friendly...


Step 1

Glacial acetic acid (150 L)+


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


Incubate for 5 min at

room temperature

pH 3 to 4

pH 3 to 4


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


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


THANK YOU...World Rhenium Congress, 2017 14

two-vial kits for the preparation of ren … b mallia radiopharmaceuticals division, radiochemistry...

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