Novel First-in-human Treatment Performed in South Africa for Painful Bone Metastases

​NTP Radioisotopes SOC Ltd, a subsidiary of the South African Nuclear Energy Corporation, in collaboration with Steve Biko Academic Hospital/University of Pretoria and their partner ITG Isotopes Technologies Garching GmbH have pioneered an exciting first-in-human anti-cancer procedure.  A promising theranostic approach, which is a combination of radiopharmaceutical diagnosis and therapy, using 68Ga-Zoledronate (for imaging) followed by 177Lu-Zoledronat

e therapy has been developed by ITG. This  method of osseous (bone) metastases treatment was recently performed in South Africa for the very first time under the leadership of Professor Mike Sathekge and his team as well as Dr Sebastian Marx and Dr Marian Meckel of ITG and Dr Otto Knoesen of NTP. The diagnostic procedure was accomplished using positron emission tomography/computed tomography (PET/CT), which is a sophisticated type of nuclear medicine imaging technique.

The global number of deaths from breast cancer is 8.2 million and 14.1 new cases were diagnosed in 2012. The number of deaths from prostate cancer is approximately 21.4 per 100,000 per year and the lifetime risk of developing cancer is approximately 14.0 percent. A serious and common consequence of prostate and breast cancer is the metastatic spread of the cancer into the bones, which causes acute bone pain and even skeletal fractures thereby tremendously reducing patients’ quality of life. Professor Sathekge explained that in the management of bone metastases the administration of bisphosphonates is an integral part of the treatment today. “Bisphosphonates have effects on the bone turnover and therefore in different ways on bone metastases. Bisphosphonates treatment is now a common part in the treatment of bone metastases since it delays the occurrence of skeletal-related events and hence showed improvements in the analgesia (pain mitigation) score.”

He added that recently one of the most effective compounds for this purpose is the nitrogen containing hetero aromats such as Zoledronate. This is a bisphosphonate that has been shown to decrease malignant skeletal destruction, severity of bone pain, and frequency of pathologic fracture.

Targeted radionuclide therapy for bone pain palliation (mainly using 89Sr and 153Sm) has long been used in nuclear medicine with excellent results in terms of pain relief and thus enhancement of the patient’s quality of life. Moreover, radionuclide treatment of bone metastases indicates a decrease in bone and tumour markers and seems to enhance overall survival rate. The therapeutic effect is based on the synergy of an increased skeletal accumulation of bone targeting agents on the metastatic foci and the nearby energy deposit of β- or α-particle irradiation.

 The new and very promising procedure for treating painful bone metastases is 177Lu(III) labelled DOTA conjugated Zoledronate. 177Lu n.c.a. is a therapeutic emitter of low energy β-particles which is commonly used in targeted radionuclide therapy. Furthermore, DOTA-Zoledronate offers the opportunity as an imaging agent in combination with the positron emitter 68Ga(III). This theranostic approach allows for a patient specific (i.e. personalised medicine) dose calculation of 177Lu- Zoledronate directly related to the patient’s individual tracer uptake profile. It is this procedure that has been pioneered by the team in South Africa and which will be of great benefit to those patients suffering the debilitating effects of metastatic bone disease.

NTP’s Eboka added that radiopharmaceuticals will continue to play a key and growing role in the assessment and therapy of numerous diseases and commended the team on their ground-breaking efforts, saying that, amongst other benefits, it will definitely add to the demand for 177Lutetium (177Lu) n.c.a., which will soon be supplied in Africa from the company’s state-of-the-art production plant based on the Necsa site at Pelindaba. “In the interim, 177Lu n.c.a. is imported routinely from ITG in Germany,” she explained. “Over 100 imaging procedures using 68Gallium (68Ga) DOTATATE and treatments employing a therapeutic radiopharmaceutical agent, 177Lu n.c.a. DOTATATE, for neuroendocrine cancer treatment have been performed at Steve Biko Academic Hospital with great success.  Furthermore, in March 2015 Professor Sathekge performed the first-in-Africa isotope-labelled theranostics procedure using 68Ga PSMA (imaging) and 177Lu n.c.a. PSMA (therapy) for prostate cancer on two patients. Several further procedures of this type have now been done and will be performed routinely in future”

Professor Sathekge and his team this month received the “Image of the Month” award made by the European Journal of Nuclear Medicine and Molecular Imaging (EJNMMI) for the excellent metastatic breast imaging study using Ga-68 PSMA which was published in the journal.  “This is another one of the first of such studies done in the world and represents leading-edge work from which NTP, Steve Biko Academic Hospital and patients in South Africa and elsewhere, especially within Africa, will greatly benefit” concluded Eboka.

Provided by: NTP Radioisotopes SOC Ltd. (www.ntp.co.za)