In vivo comparison of macrocyclic and acyclic ligands for radiolabeling of monoclonal antibodies with 177Lu for radioimmunotherapeutic applications

Radiobismuth for Therapy

“…212 Bi may be eluted selectively from the 224 Ra generator in either the chloride form or as the tetra-iodide complex. After pH adjustment this material can be used to radiolabel mAbs, peptides, or other vectors that can conjugate with a suitable bifunctional chelating agent such as C-functionalized trans-cyclohexyldiethylenetriamine pentaacetic acid derivative, CHX-A 00 DTPA ( Figure 13.2) [27][28][29][30]. …”

“…Fortuitously, a 440-keV photon emission allows real time biodistribution, pharmacokinetic, and dosimetry studies to be performed within the context of the actual half life of the therapeutic. Again, 213 Bi can be selectively eluted from an 225 Ac generator, and can readily conjugate to mAbs, peptides, or other vectors that have been modified with a suitable bifunctional chelating agent, such as CHX-A 00 DTPA [27][28][29][30].…”

“…Bifunctional chelating agents derived from DTPA include the cyclic dianhydride of DTPA [36], 1B4M-DTPA (MX-DTPA, tiuxetan) [37], and a family of trans-cyclohexyl derivatives that includes the specific stereoisomer, CHX-A 00 DTPA ( Figure 13.2) [28][29][30]. The CHX-A 00 DTPA is the only reported DTPA derivative found to form suitably stable complexes with 213 Bi and 212 Bi conjugated to mAbs or peptides in vivo [28][29][30], resulting in radioimmunoconjugates used effectively in clinical trials [27]. While the fundamental studies of the physical characteristics and coordination chemistry have not been performed on the specific enantiomeric form, CHX-A 00 DTPA, studies on the parental ligands CyDTPA and DTPA and their respective Bi(III) complexes are available [38].…”

Antibody-targeted radiation cancer therapy

“…In addition, it was reported to have similar stability with the β --emitter 177 Lu versus DOTA and PA-DOTA, the latter of which is used in clinical trials in combination with 177 Lu (REFS 11,12,31). In summary, this ligand not only provides considerable versatility for radiolabelling mAbs with the α-emitters 213 Bi and 212 Bi, but also with β --emitters such as 90 Y and 177 Lu, allowing a wider range of clinical applications 29,32,33 . 67 Cu remains an interesting candidate for therapy with regards to emission energy, half-life and imageable emissions; as such, development of the chemistry remains active 34 .The choice of BCA for 67 Cu remains an open and unresolved topic; several different macrocyclic chelating agents have been touted as stable and inert with 67 Cu, despite reports of transchelation to superoxide dismutase and detection in patients' ceruloplasmin [35][36][37] .…”

Targeting of Radio-Isotopes for Cancer Therapy

“…The CHX-A'' ligand might provide considerable versatility for radiolabeling mAbs with not only the α-emitters 213 Bi and 212 Bi, but also then the β-emitters, 90 Y and 177 Lu, to provide a wider range of radionuclides for clinical applications. 37,39,40 Thus, there is a clear balancing of properties that has to be struck to achieve a reasonable radiolabeled final product that can be prepared within an acceptable time frame yet also possess adequate stability of the metal complexes within the boundary conditions set by half-life of the isotope and the biological milieu. Several Cu(II) isotopes have been investigated with 67 Cu for targeted radiation therapy being foremost.…”