By administering 195mPlatinum radiolabeled cisplatin ([195mPt]cisplatin) to cancer patients, the researchers aim to identify individuals who will benefit from the therapy, as well as those who will not, sparing them from potentially ineffective and harmful treatments.
Cisplatin is a chemotherapy drug that is widely used in the treatment of various types of cancer. It belongs to a class of medications known as platinum-containing compounds. Cisplatin works by interfering with the DNA inside cancer cells, ultimately disrupting their ability to divide and grow. By binding to the DNA, it forms cross-links between the DNA strands, leading to the formation of DNA adducts. These adducts prevent the cancer cells from replicating their DNA and undergoing cell division, which inhibits their growth and eventually causes their death.
Cisplatin is particularly effective against rapidly dividing cells, such as cancer cells, but it can also affect some healthy cells that divide quickly, such as those in the bone marrow, hair follicles, and digestive tract. This is why cisplatin treatment can have side effects, including bone marrow suppression, hair loss, nausea, and kidney damage.
Despite its long history of use, predicting which patients will respond positively to cisplatin treatment remains challenging. In addition, its precise distribution within the human body remains a mystery.
According to Dr. Wouter Vogel, a nuclear medicine specialist at NKI, the tumor-uptake of cisplatin varies greatly across patients, and whether this variability correlates with its efficacy is still unknown. Dr. Vogel explains, “By making cisplatin radioactive, we can track its movements in cancer patients and hopefully evaluate its effectiveness. Additionally, this technique may shed light on adverse events, particularly nephrotoxicity.”
Notably, cisplatin only improves the two-year survival rate by 5-10% on average. Dr. Vogel emphasizes that many patients derive no benefit from cisplatin, yet may suffer from its adverse effects. He states, “Being able to predict treatment response would be immensely valuable, sparing patients from potentially ineffective yet harmful therapy.”
This innovative approach aligns with the growing trend toward precision medicine, which aims to replace the outdated “one size fits all” treatment model. Professor Harry Hendrikse, a clinical pharmacologist at Amsterdam UMC, VUmc, highlights the benefits of precision medicine, stating, “Not only does it provide personalized treatment for patients, ensuring they receive the best care promptly, but it also holds significant pharmaco-economic advantages. Clinicians can use costly targeted oncology treatments exclusively on patients who will benefit from them.”
The first scientific research endeavor, titled “Preclinical imaging characteristics and quantification of Platinum-195m SPECT,” was initiated by Dr. Else Aalbersberg, a technical medical specialist at NKI. This study served as the foundation for the ongoing clinical pilot study utilizing [195mPt]cisplatin or CISSPECT®.
Dr. Aalbersberg explains, “We began preparations for this investigation almost a decade ago in collaboration with the Nuclear Research and Consultancy Group (NRG), who developed CISSPECT®. It took us two years to reach this stage of the study."
Organizing a study involving radioactive chemotherapy proved to be a complex task, but the proximity of the reactor, the GMP-compliant laboratory where the radiopharmaceutical [195mPt]cisplatin is prepared, and the hospital where patients receive treatment, all within 100 kilometers, is a truly unique advantage that facilitated the research.
The initial phase of the study is currently in progress, with five lung cancer patients already receiving [195mPt]cisplatin out of the intended six participants. The researchers assume that if [195mPt]cisplatin does not seem to accumulate within the tumor, as observed through scans, it is unlikely to be effective.
After administration, patients do not need to remain in the hospital; instead, the scans are conducted during the interval between chemotherapy and radiotherapy. Dr. Aalbersberg reports, "We are pleased with the preliminary results; they are promising. Similar studies have been conducted by colleagues in South Africa, albeit on healthy volunteers. We look forward to comparing our findings with theirs to enhance our understanding.”
Dr. Vogel emphasises the research is in an early state and positive results will need to be validated in additional clinical trials.
For more information, contact Professor Harry Hendrikse, or read the following publication:
Aalbersberg EA, et al. (2023) Preclinical imaging characteristics and quantification of Platinum-195m SPECT. Eur J Nucl Med Mol Imaging 44:1347-1354. https://doi.org/10.1007/s00259-017-3643-2.
