Abstract:
Platinum 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 195mPt-cisplatinum (commonly referred to as cisplatin) for a clinical pilot study on healthy volunteers. Enriched 194PtCl2 was prepared by digestion
of enriched 194Pt metal (>95%) followed by thermal decomposition over a 3 h period. The 194PtCl2 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.
195mPt(NH3)2I2, formed with the addition of KI and NH4OH, was converted to the diaqua species [195mPt(NH3)2(H2O)2]2+ by reaction
with AgNO3. The conversion to 195mPt-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±2.5MBq/mg at end of synthesis) than previously found (5MBq/mg). Volunteers received between 108 and 126MBq of radioactivity, which is equivalent to 6.8–10.0mg
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 goodmanufacturing 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 cisplatinumremained in blood pools at 5 h,which gradually cleared over the 6-daymonitoring 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.
