###### Abstract  
Designing and implementing various radionuclide production methods guarantees a sustainable supply, which is important for medical use. The use of medical cyclotrons for radiometal production can increase the availability of gallium-68 (\({}^{68}\)Ga) radiopharmaceuticals. Although generators have greatly influenced the demand for \({}^{68}\)Ga radiopharmaceuticals, the use of medical cyclotrons is currently being explored. The resulting \({}^{68}\)Ga production is several times higher than obtained from a generator. Moreover, the use of solid targets yields end of purification and end of synthesis (EOS) of up to 194 GBq and 72 GBq, respectively. Furthermore, experiments employing liquid targets have provided promising results, with an EOS of 3 GBq for [(\({}^{68}\)Ga)]Ga-PSMA-11. However, some processes can be further optimized, specifically purification, to achieve high \({}^{68}\)Ga recovery and apparent molar activity. In the future, \({}^{68}\)Ga will probably remain one of the most in-demand radionuclides; however, careful consideration is needed regarding how to reduce the production costs. Thus, this review aimed to discuss the production of \({}^{68}\)Ga radiopharmaceuticals using Advanced Cyclotron Systems, Inc. (ACSI, Richmond, BC, Canada) Richmond, Canada and GE Healthcare, Wisconsin, USA cyclotrons, its related factors, and regulatory concerns. cyclotron targety; radiopharmaceutical; solid target; liquid target; Good Manufacturing Practices (GMP) +
Footnote †: journal:  
Developments in PET imaging for prostate cancer (PCa) with radiolabeled [\({}^{68}\)Ga]Ga-PSMA-11 have also attracted the interest of nuclear medicine physicians [8; 9; 10]. The product was approved in 2020 [11], making it the third \({}^{68}\)Ga-based product approved by the USFDA in 5 years. The \({}^{68}\)Ga-based radiopharmaceuticals have been increasingly well-known due to the superior quality of PET imaging over single photon emission computed tomography [12; 13], expanding the knowledge about gallium radiochemistry and, most importantly, \({}^{68}\)Germanium/\({}^{68}\)Gallium (\({}^{68}\)Ge/\({}^{68}\)Ga) generator availability. Recent developments combining \({}^{68}\)Ga with therapeutic radionuclides such as lutetium-177 (\({}^{177}\)Lu) for theranostic application in both NET and PCa [14; 15; 16] further increase the demand for \({}^{68}\)Ga-based radiopharmaceuticals. The main source of \({}^{68}\)Ga in many nuclear medicine facilities is the \({}^{68}\)Ge/\({}^{68}\)Ga generator (Figure 1B). The short-lived daughter isotope is eluted with hydrochloric acid, resulting in a high activity with a low \({}^{68}\)Ge breakthrough. Depending on the type and age of the generator, between 0.74 GBq and 3.7 GBq of \({}^{68}\)Ga activity is produced per elution, and the generator can be operated for 1 year, albeit with a limited yield [17]. In addition to the generator, the \({}^{68}\)Ga produced in the cyclotron has recently received more attention due to (1) the cost and uncertainty of a constant supply of \({}^{68}\)Ge/\({}^{68}\)Ga generators and (2) the upsurge of medical cyclotrons worldwide [18; 19]. Two promising production methods using medical cyclotrons are \({}^{68}\)Zn(p,n)\({}^{68}\)Ga and \({}^{65}\)Cu(\(\alpha\),n)\({}^{68}\)Ga reactions. The first method can be performed with a small medical cyclotron [20] and provide a highly specific activity suitable for routine production and radiopeptide labeling [21; 22; 23]. The production of \({}^{68}\)Ga-labeled peptides from a medical cyclotron (Figure 2) involves four main steps: (1) target preparation; (2) proton irradiation; (3) dissolution, purification, and separation of target material; and (4) radiolabeling of \({}^{68}\)Ga-labeled peptides. The production of \({}^{68}\)Ga via the \({}^{68}\)Zn(p,n)\({}^{68}\)Ga nuclear reaction results in the co-production of \({}^{66}\)Ga and \({}^{67}\)Ga [24].