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| ABSTRACT |
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| Year : 2011 | Volume
: 26
| Issue : 5 | Page : 53-54 |
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Therapy
| Date of Web Publication | 9-Dec-2011 |
Correspondence Address:
 Source of Support: None, Conflict of Interest: None  | Check |
How to cite this article:
. Therapy. Indian J Nucl Med 2011;26, Suppl S1:53-4 |
Therapy-1
Effect of phosphorous - 32 glass microspheres in hepatocellular carcinoma recurrence after tumor resection
D Priya, P Aarthy, K Vidhya, M Chandran
Department of Biotechnology, Veltech Hightech Dr. Rangarajan Dr. Sakunthala Engineering College, Avadi, Chennai, India
Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in South Asian countries, Prevention of cancer recurrence and metastasis after curative surgical resection has become a key issue for improvement of the surgical outcome and long-term survival of the patients. Objective: To evaluate the preventive effects of phosphorus- 32 glass microspheres (P32-GMS) in the recurrence of massive hepatocellular carcinomas (HCCs) after tumor resection. Materials and Methods: Twenty-nine patients with massive HCCs received local P32-GMS implantation after liver tumors were removed, while the other 38 patients with massive HCCs were not treated with P32-GMS after hepatectomies. The radioactivity of the blood, urine and liver were examined. The complications, HCC recurrence and overall survival rates in the patients were analyzed. Results: P32-GMS implanted in the liver did not cause systemic absorption of P32. There were no significant differences of postoperative complications between the patients with and without P32-GMS treatment. The shortterm (six months and 1 year) and long-term (2, 3 and over 3 years) recurrence rates in patients who received P32-GMS radiotherapy were significantly decreased, and the overall survival rates in this group were significantly improved. Conclusion: P32-GMS implantation in the liver can significantly decrease the postoperative recurrence and improve the overall survival in HCCs patients after hepatectomy. This therapy may provide an innovative method in prevention of HCC recurrence after operation.
Therapy-2
Bioevaluation of BARC 125 I OCU-PROSTA Seeds for prostate cancer treatment
Archana Mukherjee, Haldhar Dev Sarma 1 , Sanjay Saxena, Yogendra Kumar, Pradip Chaudhari 2 , Jayant Sastri Goda 2 , Grace Samuel, Ashutosh Dash,
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, 1 Animal House Facility, Bhabha Atomic Research Centre, Mumbai, 2 Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India
Introduction: Permanent implant brachytherapy (PIB) is widely used for the treatment of early stage prostate cancer either as monotherapy or in combination with EBRT in patients with significant risk of extra prostatic extension. A technology for the development of the sources indigenously was developed and "BARC 125 I OCU-PROSTA Seeds" are currently used for the treatment of ocular cancer. The extension of their use in prostate cancer is desirable as there is a large demand for such sources in India. Objective: Preclinical evaluation of indigenously prepared "BARC 125 I OCU-PROSTA Seeds" for the treatment of prostate cancer. Materials and Methods: "BARC 125 I OCU-PROSTA Seeds" were prepared by adsorbing 125 I on palladium coated silver rods of 0.5 mm(φ) x 3mm(l) size. The activity of radioactive sources after the adsorption was measured by using a pre-calibrated ion chamber after washing with warm distilled water. The bare radioactive sources were coated with polystyrene and were subsequently sealed within titanium capsules of dimension 0.8 mm (φ) x 4.75 mm (l) using Nd:YAG laser. The uniform distribution of activity on source core was ascertained by autoradiography. The inactive sources encapsulated were checked for visualization by sonography and were tested for smooth passage through MICK needles of MICK applicators used for insertion of seeds in human prostate. 125 I Seeds (2 Nos, Activity ~ 370μCi/13MBq of 125 I) were inserted surgically in the prostate gland of normal rabbits. In-vivo leakage of activity in blood from the implanted seeds was studied by measurement of radioactivity in blood drawn at various time points. The activity was measured in a NaI (Tl) gamma scintillation counter for 125 I activity. To study migration of the seeds from the implanted site to other tissues, CT Imaging was done at periodic intervals i.e. 2 nd and 15 th day and 1, 2, 3, 4, 5 and 6 months after implantation. CT imaging was performed under anesthesia (Ketamine 50mg/Kg and Xylaxine 10mg/Kg) and positioning was done using immobilization device with anatomical markers; so as to exactly calculate the migration of the seeds. Implanted seeds were recovered from the animal after completion of the study. Results: BARC 125 I OCU-PROSTA seeds were implanted successfully in the prostate of rabbit. Blood was counted for 125 I activity and counts equal to background were observed. No leakage of activity was observed indicating integrity of seeds. Both the seeds were observed in the prostate region during the entire period of the study (6 months) in CT images of prostate region. The seeds were intact with no apparent damage after recovery. The radioactivity associated with the seed was estimated after 9 months that accounted for the decay loss and no leakage of activity. No surface contamination was observed on the recovered seed. Conclusion: Preclinical evaluation of "BARC 125 I OCU-PROSTA Seeds" carried out indicated that the seeds are suitable for taking it to clinical trials.
Therapy-3
Synthesis and biological evaluation of 90 Y-labeled porphyrin-DOTA conjugate for targeted tumor therapy
Sweety Singhal, Mohini Bhadwal, Tapas Das, Sudipta Chakraborty, Haladhar Dev Sarma 1 , Rubel Chakravarty, Ashutosh Dash, Sharmila Banerjee
Radiopharmaceuticals Division, 1 Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, India
Introduction: Development of tumor-avid substances has received considerable attention in current cancer diagnostic and therapeutic protocols. Among the various substances exhibiting tumor specificity, hematoporphyrin and its derivatives have been extensively investigated with the aim to identifying potential agents for targeted tumor diagnosis and therapy. Working in this direction, a water soluble unsymmetrical porphyrin, namely 5-(4-(3-amino)-n-propyloxyphenyl)-10,15,20-tris-(4-carboxymethyleneoxyphenyl)porphyrin was synthesized and subsequently coupled with a bi-functional chelating agent (BFCA), namely p-isothiocyanato-benzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid [p-NCS-benzyl-DOTA], for its radiolabeling with 90 Y. 90 Y was chosen as a therapeutic radionuclide owing to its suitable nuclear decay characteristics (Eβmax =2.28 MeV, T 1/2=64 h) and easy availability in high radionuclidic purity from a 90 Sr- 90 Y generator. The emission of high energy β- particle makes it a suitable candidate for therapy in large-sized tumors. Materials and Methods: The unsymmetrically substituted porphyrin used for the present study was synthesized by a multi-step reaction sequence. The product was purified over silica-gel column and fully characterized by 1 H-NMR and IR spectroscopy. Bearing in mind the high thermodynamic and kinetic stability of Y +3 -DOTA complex, the amino group of the porphyrin derivative was then coupled with p-NCS-benzyl-DOTA. The crude product thus obtained was purified by preparative TLC and the purified product i.e. porphyrin-DOTA conjugate, was characterized by 1 H-NMR and IR spectroscopy. The BFCA coupled porphyrin derivative was radiolabeled by incubating a solution of the conjugate (100 μg) in 0.1 M NH 4 OAc buffer (pH 4-5) with 90 YCl 3 (20 μL) at 60-70 0 C for 1 h. 90 Y used in the present study was obtained from an in-house electrochemical 90 Sr- 90 Y generator. The 90 Y-DOTA-porphyrin complex was characterized by paper chromatography using 50% aqueous acetonitrile as developing solvent and reverse phase HPLC employing gradient elution technique using water and acetonitrile mixtures (1:1 v/v) containing 0.1% trifluoroacetic acid as the mobile phase. Furthermore, in-vivo studies in fibrosarcoma tumor-bearing Swiss mice were carried out at 4 different time points to explore the potential of this novel 90 Y-labeled porphyrin-DOTA conjugate. Results and Discussion: The formation of porphyrin ring was confirmed by UV-VIS spectrum. Moreover, in 1 H NMR spectrum a singlet observed at high field (δ= -2.89 ppm, 2 NH protons) further confirms the formation of the porphyrin ring. Porphyrin-DOTA conjugate was obtained in ~80% yield and its formation was ascertained from the satisfactory 1 H-NMR spectrum. Carrier-free 90 Y with high radionuclidic purity (30.23±15.21 KBq of 90 Sr per 37 TBq of 90 Y) was obtained from an electrochemical 90 Sr- 90 Y generator. The radiolabeling yield of 90 Y-DOTA-porphyrin-conjugate was found to be ~85% as observed by paper chromatography and HPLC. Biodistribution studies showed good tumor uptake (3.19% ID/g, ID: Injected Dose) within 30 min post-injection (p.i.) and retention of activity in tumor was observed till 24 h p.i. (1.48% ID/g), upto which the preliminary studies were continued. The complex exhibited favorable tumor/blood and tumor/muscle ratios. The radiolabeled conjugate exhibited fast renal clearance with insignificant uptakes in the major non-target organs/tissues. Conclusion: Interesting results obtained in preliminary biodistribution studies warrants further evaluation of the potential of the 90 Y-labeled porphyrin-DOTA for targeted tumor therapy.
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