Novel bispidine skeleton has been extensively designed as bifunctional chelators
(BFCs) for their special stereochemical structure and variable dentate numbers. Bispidinebased
ligands (BBLs) as BFCs generally integrate the benefits of conventional acyclic and
macrocyclic BFCs, demonstrating exceptional radiolabeling kinetics, thermodynamic stability
and kinetic inertness for their metal complexes. The accessible inherent spatial
asymmetry in bispidine skeleton is well-suited for Jahn-Teller active metal ions, notably
Cu(II). Currently, BBLs have already been studied to coordinate with radionuclides such as
<sup>52</sup>Mn, <sup>64/67</sup>Cu, <sup>68</sup>Ga, <sup>111</sup>In, <sup>133</sup>La, <sup>177</sup>Lu, <sup>212</sup>Pb, <sup>212/213</sup>Bi, and <sup>225</sup>Ac for radiopharmaceuticals
application. Among them, the <sup>64</sup>Cu, <sup>52</sup>Mn, <sup>111</sup>In, <sup>177</sup>Lu, and <sup>225</sup>Ac complexes with BBLs have
particularly made significant research progress. In this review, we introduce the synthesis
of BBLs and their applications in chelating the above five metallic radionuclides for the development of radiopharmaceuticals
are discussed.