1. Microsphere cold kit for Selective Intra-arterial Radionuclide Therapy (SIRT)
Dr. Jaya Shukla
Additional Professor, PGIMER, Chandigarh
The product is for the treatment of large/ unresectable liver cancer
And is ready to commercialize

2. Provide cost effective treatment of liver cancer
Vision
Current issue
More than 8.4 lakh new cases of liver cancer in 2018 across the world*, more than 50,000 new cases diagnosed in India
Due to lack of symptoms, patients often present with advanced stage
Surgery are not possible due to size, location and spread of tumor
Available options are expensive
Proposed solution
Provide cost effective treatment of liver cancer
*Source: American Institute for Cancer Research

3. Proposed solution: Value Proposition
Y-90 Sirtex/Therespheres
Commercially available, ready to use
Y-90 is for therapy only
Dose estimation not possible. Separate procedure is required
Particulate
Two day procedure
Large sized particles (20-30 µm) may cause delivery reflux
Stable
Product cost: Highly expensive (lakhs)
Re-188 lipiodol
Re-188 Microspheres
Non-radioactive microsphere kit
Can determine dosage quantity to minimize peripheral organ damage
Labelling yield is ≥90%
Small size particles (~5 µm) – easy to deliver, no reflux
Single day procedure
Very stable
Product cost: 1% of Y-90 Spheres
Commercially available nonparticulate non-radioactive kit
Labelling yield is %
Non-particulate
Not very stable, i.e. may leave from liver, excretes with urine
Product cost: Relatively less expensive)
Ref: RSNA 2005; 25:41-55
Ref: J Nucl Med 2005; 46:
Ref: Clin Nucl Med. 2019;44: e93–5

4. Product features Market ready Patent pending
Easy to prepare – mix & use
Freeze dried
Shelf life more than 1 year
Easy to administer due to smaller size
Product features

5. Appendix

6. Therapy Liver has dual blood supply Hepatic artery and portal vein
Normal liver gets 80% of blood supply from portal vein and 20% from hepatic artery
However, Liver cancer gets
80% blood supply from hepatic artery and 20% by portal vein
Dual blood supply property is exploited to deliver radioactive compounds through hepatic artery
Trans-arterial delivery of treatment
Tumor also form collaterals and communicates with adjacent organs
For radiation delivery, pretherapy assessment is important and done using γ emission
Radioactive microspheres delivered to tumor results in effective tumor damage, while limiting the radiation injury to the normal liver

7. Radio isotopes Rhenium-188 (Re-188) Yttrium-90 (Y-90)
Obtained from transportable W-188/Re-188 generator
Produced from decay of the reactor-produced W parent (T1/2-69 days)
Re-188 is a high energy beta-emitting radioisotope
Βmax: 2.12 MeV,
γ: 155 keV
T1/2: hrs
Decays to Os-188
Shelf-life: 6 months
Cost effective
Yttrium-90 (Y-90)
Cyclotron produced
Y-90 is a pure β emitter
Pretherapy assessment not possible
βmax-2.2Mev, T1/2-64 h, No gamma (γ) photons for imaging
costly

8. Mix & use non-radioactive kit
A lyophilized kit has been developed
Kits are stable up to one year
Tc-99m or Re-188 is incorporated into the reconstituted microspheres by heating at 100 °C for 30 min
Free Re-188 is separated by 5 min centrifugation post labeling
Radiolabeling yield is above 90%
Radiochemical purity is above 99%
Stability after radiolabellig is studied up to 96 h

9. Patients Study Protocol
A informed written consent from patient and attendant
Trans-arterial catheter is placed by interventional radiologist
Scout dose ( MBq)
188Re-Microspheres (Pellet) + Req. vol. of contrast
Lipiodol may be added to visualize delivery of microspheres
Image at 140 keV/155 keV photo peak (±20% window) Anterior and posterior whole body/3-min static chest , SPECT/CT Chest (optional)
Geometric means of counts in the liver, Lung, spleen & tumor Calculation of lung shunt
Administer dose; WB Image at 24 and 48 hr
and SPECT/CT Chest at 24 hr/48 hr
Just before therapy:
55Y/F, HCV related cirrhosis, HCC BCLC-C
Left lobe-13.8x9.8x8.4 cm, left branch PVT
3.5 mCi Re-188 microspheres were administered for lung shunt study
Geometric means (GM) of Lung, liver +spleen counts are calculated
lung shunt =
GM lungs
GM lung + liver + spleen
x 100 = 16%

10. Distribution of microspheres
To observe gastro-dudonal reflex
Abdomen SPECT/CT
To observe Lung shunt
Lung SPECT/CT
Note: good localization in tumor is abserved. No gastro-dudonal reflex and no lung activity is noted

11. Re-188 microsphere SIRT (D) (E) (F) (G) (A) (C) (B)
Patient underwent selective internal radiation therapy (SIRT) using indigenously prepared Re-188-microspheres (80 mCi), (A) shunt calculation-Tc-99m-microsphere (1.5%); (B) whole body image 24hr post SIRT; (C) SPECT/CT at 24 h post SIRT; (D) and (E) Ga-68-DOTATATE pre therapy PET/CT and CT; (F) and (G) PET/CT and CT; after 6 months of SIRT treatment showing complete disappearance of the liver lesion. Patient is surviving after more than 1.5 year post SIRT

12. Publications
Shukla J, Kalra N, Kumar R, Bhusari P, Chhabra A, Parmar M, Vatsa R, Singh H, Duseja a, mittal BR. Two cases of Rhenium-188 microspheres for inoperable hepatocellular carcinoma. Clin Nucl Med, 2019;44: e93–5. DOI /RLU (IF-6.309).
.Vadi SK, Mittal BR, Kumar R, Parihar AS, Shukla J, Kalra N. Demonstration of treatment response to trans-arterial radio-embolization (TARE) on 68Ga-DOTANOC PET/CT in a patient with metastatic neuroendocrine tumor. Clinical Nuclear Medicine 43 (9), e312-e313. doi: /RLU (IF-6.309).
Shukla J, Kalra N,  Bhusari P,  Vatsa R, Duseja A, Dhiman R, Mittal BR, Agrawal K. 188Re-microspheres for selective intra-arterial radionuclide therapy (SIRT) in patients with HCC: Feasibility study. J Nucl Med 2015 56:1242.
Patents:
Indian: Published
International: PCT/IN2019/050304