Skeletal-related events due to bone metastases can be prevented by early diagnosis using radiological or nuclear imaging techniques. Nuclear medicine techniques such as Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) have been used for diagnostic imaging of bone for decades. Although it is widely recognized that conventional diagnostic imaging techniques such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) have high sensitivity, low cost and wide availability, the specificity of both techniques is rather low compared to nuclear medicine techniques. Nuclear medicine techniques, on the other hand, have improved specificity when introduced as a hybrid imaging modality, as they can combine physiological and anatomical information. Two main radiopharmaceuticals are used in nuclear medicine: [99mTc]-methyl diphosphonate ([99mTc]Tc-MDP) from the generator and [18F]sodium fluoride ([18F]NaF) from the cyclotron. The former is used in SPECT imaging, while the latter is used in PET imaging. However, recent studies show that the role of radiolabeled bisphosphonates with gallium-68 (68Ga) and fluorine-18 (18F) may have a potential role in the future. This review, therefore, presents and discusses the brief method for producing current and future potential radiopharmaceuticals for bone metastases.
Due to increased demand, cyclotron has an expanding role in producing Gallium-68 (68Ga) radiopharmaceuticals using solid and liquid targets. Though the liquid target produces lower end-of-bombardment activity compared to the solid target, our study presents the performance of 68Ga radiopharmaceuticals production using the liquid target by evaluating the end-of-bombardment activity and the end-of-purification activity of [68Ga]GaCl3. We also present the effect of increasing irradiation time, which significantly improves the end-of-synthesis yield. From the result obtained, the end-of-bombardment activity produced was 4.48 GBq, and the [68Ga]GaCl3 end-of-purification activity produced was 2.51 GBq with below-limit metallic impurities. Increasing the irradiation time showed a significant increase in the end-of-synthesis activity from 1.33 GBq to 1.95 GBq for [68Ga]Ga-PSMA-11 and from 1.13 GBq to 1.74 GBq for [68Ga]Ga-DOTA-TATE. Based on the improvements made, the liquid target production of 68Ga radiopharmaceuticals is feasible and reproducible to accommodate up to 5 patients per production. In addition, this work also discusses the issues encountered, together with the possible corrective and preventative measures.