Production of high specific activity Pt-195m-cisplatinum at South African Nuclear Energy Corporation for phase 0 clinical trials in healthy individual subjects

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dc.contributor.authorZeevaart, JRen_AU
dc.contributor.authorWagener, Jen_AU
dc.contributor.authorMarjanovic-Painter, Ben_AU
dc.contributor.authorSathekge, Men_AU
dc.contributor.authorSoni, Nen_AU
dc.contributor.authorZinn, Cen_AU
dc.contributor.authorPerkins, Gen_AU
dc.contributor.authorSmith, SVen_AU
dc.date.accessioned2019-11-12T03:17:41Zen_AU
dc.date.available2019-11-12T03:17:41Zen_AU
dc.date.issued2013-07-23en_AU
dc.date.statistics2019-11-12en_AU
dc.description.abstractPlatinum agents continue to be the main chemotherapeutic agents used in the first-line and second-line treatments of cancer patients. It is important to fully understand the biological profile of these compounds in order to optimize the dose given to each patient. In a joint project with the Australian Nuclear Science and Technology Organisation and the Nuclear Medicine Department at Steve Biko Academic Hospital, South African Nuclear Energy Corporation synthesized and supplied (195m) Pt-cisplatinum (commonly referred to as cisplatin) for a clinical pilot study on healthy volunteers. Enriched (194) PtCl2 was prepared by digestion of enriched (194) Pt metal (>95%) followed by thermal decomposition over a 3 h period. The (194) PtCl2 was then placed in a quartz ampoule, was irradiated in SAFARI-1 up to 200 h, then decay cooled for a minimum of 34 h prior to synthesis of final product. (195m) Pt(NH3 )2 I2 , formed with the addition of KI and NH4 OH, was converted to the diaqua species [(195m) Pt(NH3 )2 (H2 O)2 ](2+) by reaction with AgNO3 . The conversion to (195m) Pt-cisplatinum was completed by the addition of concentrated HCl. The final product yield was 51.7% ± 5.2% (n = 5). The chemical and radionuclidic purity in each case was >95%. The use of a high flux reactor position affords a higher specific activity product (15.9 ± 2.5 MBq/mg at end of synthesis) than previously found (5 MBq/mg). Volunteers received between 108 and 126 MBq of radioactivity, which is equivalent to 6.8-10.0 mg of carrier cisplatinum. Such high specific activities afforded a significant reduction (~50%) in the chemical dose of a carrier cisplatinum, which represents less than 10% of a typical chemotherapeutic dose given to patients. A good manufacturing practice GMP compliant product was produced and was administered to 10 healthy volunteers as part of an ethically approved Phase 0 clinical trial. The majority of the injected activity 27.5% ± 5.8% was excreted in the urine within 5 h post injection (p.i.). Only 8.5% ± 3.1% of cisplatinum remained in blood pools at 5 h, which gradually cleared over the 6-day monitoring period p.i. At the end of the study (6 days p.i.), a total of 37.4% ± 5.3% of the product had cleared from the blood into urine, and approximately 63% remained in the body. The significantly lower concentration of carrier cisplatinum used for imaging resulted in a well-tolerated product. © 2013 John Wiley & Sons, Ltd.en_AU
dc.identifier.citationZeevaart, J. R., Wagener, J., Marjanovic‐Painter, B., Sathekge, M., Soni, N., Zinn, C., Perkins, G., & Smith, S. V. (2013). Production of high specific activity 195mPt‐cisplatinum at South African Nuclear Energy Corporation for Phase 0 clinical trials in healthy individual subjects. Journal of Labelled Compounds and Radiopharmaceuticals, 56(9-10), 495-503. http:/dx.doi.org/10.1002/jlcr.3091en_AU
dc.identifier.govdoc8914en_AU
dc.identifier.issn0362-4803en_AU
dc.identifier.issue9-10en_AU
dc.identifier.journaltitleJournal of Labelled Compounds and Radiopharmaceuticalsen_AU
dc.identifier.pagination495-503en_AU
dc.identifier.urihttp:/dx.doi.org/10.1002/jlcr.3091en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/9085en_AU
dc.identifier.volume56en_AU
dc.language.isoenen_AU
dc.publisherWileyen_AU
dc.subjectDiagnosisen_AU
dc.subjectMedicineen_AU
dc.subjectClinical trialsen_AU
dc.subjectPlatinumen_AU
dc.subjectChemotherapyen_AU
dc.subjectRadiation chemistryen_AU
dc.subjectCarriersen_AU
dc.subjectBlooden_AU
dc.titleProduction of high specific activity Pt-195m-cisplatinum at South African Nuclear Energy Corporation for phase 0 clinical trials in healthy individual subjectsen_AU
dc.typeJournal Articleen_AU
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