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Pervez, Shahid (2004) RADIOLABELING OF MOLECULES AND THEIR QUALITY CONTROL FOR MEDICAL USE. PhD thesis, Bahauddin Zakariya University, Multan.



Lanreotide, a synthetic octapeptide analog of a native hormone somatostatin, was labeled with a commonly available, inexpensive radionuclide 99mTc. Labeling was accomplished by reduction of the cysteine bridge, which provided sulfhydryl groups for chelation with 99mTc. Stannous chloride was used as reducing agent, while tartrate acted as transchelating agent. Lanreotide (100µg), stannous chloride dihydrate (100µg) and tartaric acid (64µg) were dissolved in acetate/acetic acid buffer (pH 2.8). After overnight (~18h) incubation, -444MBq (l2mCi) 99mTc was added and kept in boiling water for 30 min. More than 97 % labeling efficiency was confirmed by RP-HPLC, ITLC-SG and C18 cartridge analysis. Radiolabeling results in one major peak when analyzed by reverse-phase HPLC. The stability of the 99mTc-peptide bond was evaluated by cysteine challenge studies. Lanreotide was also labeled with Iodine-1 31; the most widely used therapeutic and easily available radionuclide. Radioiodination of lanreotide was carried out by chloramine-T and Iodogen methods. Chloramine-T and Iodogen were used as oxidizing agents to form some electrophilic iodine species, which then labels the tyrosine of lanreotide. The radiolabeling yield varied between 40 to 80 %. Chloramine-T method was found more suitable than Iodogen method, because nearly 25 % of the initial iodine activity was adsorbed on Iodogen coating. Thin layer chromatography and high performance liquid chromatography techniques were used for monitoring the complexation of 131I with lanreotide and stability and purity of 131I-lanreotide. Hydroxyapatite (HA), a natural constituent of bone, was synthesized. HA particles were radio labeled with 188Re. Radiolabeling efficiency was ~95 %. In vitro studies showed 5% loss of activity from particles in normal saline over a period of 2 days, whereas a dissociation rate of 9 % was observed in human serum albumin. Labeling of HA particles is dependent on the use of 188Re complexed with hydroxyethylidenediphosphonate (HEDP). Labeling was independent of the emulsifier. The ease and efficiency with which HA carrier is labeled, coupled with observed low leakage rates, make radiolabeled HA particles an attractive candidate as a radiation synovectomy agent for evaluation in rheumatoid arthritis. The preparation of 188Re-glucoheptonate (GH) is described using 188Re, which was obtained from an alumina based 188W/188Re generator. The dependence of the radiolabeling yields of 188Re-Gh on reducing agent concentration, GH concentration, pH, temperature and incubation time was examined. In the case of optimum conditions the yield of 188Re-GH was ~99 %. The ITLC technique was employed to monitor the different species formed. A biodistribution study of 188Re-GH was carried out in rats and compared to the biological behavior of 99mTc-GH. The in vivo tissue distribution in Sprauge-Dawley rats shows no significant differences to188Re and 99mTc glucoheptonates. Addition of Re carrier (50 µg NH4ReO4) has a significant effect on the rate of complexation and stability of 188Re-glucoheptonate. The synthesis of 188Re-MAG3 is described using 188Re, which was obtained from the alumina based 188W/188Re generator. Dependence of the radio labeling yields of 188Re-MAG3 on reducing agent concentration, Bz-MAG3 concentration, pH, temperature and incubation time was examined. In the case of optimum conditions the yield of 188Re-MAG3 was 98 %. After optimizing reaction conditions a freeze-dried kit was formulated. TLC and HPLC techniques were employed to monitor the different species formed. Biodistribution study of 188Re-MAG3 was carried out in rats and compared with behavior of 99mTc-MAG3. The pharmacokinetics behavior of 188Re-MAG3 and 99mTc-MAG3 in rats was identical, hence 188Re-MAG3 is quite suitable for intracoronary radiation therapy and the dose to critical organs is minimal in case of balloon rupture. Bone seeking radiopharmaceuticals such as ethylenediaminetetramethylene phosphonate (EDTMP) complexes of 153Sm and 166Ho are receiving considerable attention for therapeutic treatment of bone metastases. Rhenium-188 has both beta-particle emissions for a therapeutic effect and gamma-emission for imaging and it is available from an in-house generator system similar to the current 99mTc generator, which makes it convenient for clinical use. The preparation of 188Re-EDTMP is described using 188Re, which was obtained from the alumina-based 188W/188Re generator. Dependence of the radiolabeling yield of 188Re-EDTMP on reducing agent concentration, EDTMP concentration, incubation time, pH and addition of carrier was examined. In the case of optimum conditions, the radio labeling yields of 188Re- EDTMP were ~98 % for carrier-free as well as carrier-added 188Re. The addition of ascorbic acid plays an important role in the stability of carrier-free as well as carrier added 188Re-EDTMP preparations. The biodistribution of carrier-free and carrier-added 188Re-EDTMP compounds in rats was also studied. The results show that 188Re (carrier-added)-EDTMP is a potential bone pain palliation radiopharmaceutical due to its high skeletal uptake, rapid blood clearance and relatively low soft tissue absorption

Item Type:Thesis (PhD)
Uncontrolled Keywords:radiolabeling, lanreotide, somatostatin, nuclear medicine, radionuclides, technetium-99m, radioiodine, radiorhenium
Subjects:Physical Sciences (f) > Chemistry(f2)
ID Code:1423
Deposited By:Mr. Muhammad Asif
Deposited On:26 Mar 2007
Last Modified:04 Oct 2007 21:06

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