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Comparison of two cross-bridged macrocyclic chelators for the evaluation of 64Cu-labeled-LLP2A, a peptidomimetic ligand targeting VLA-4-positive tumors

Jiang, Majiong ; Ferdani, Riccardo ; Shokeen, Monica ; Anderson, Carolyn J

Nuclear Medicine and Biology, February 2013, Vol.40(2), pp.245-251 [Peer Reviewed Journal]

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  • Title:
    Comparison of two cross-bridged macrocyclic chelators for the evaluation of 64Cu-labeled-LLP2A, a peptidomimetic ligand targeting VLA-4-positive tumors
  • Author: Jiang, Majiong ; Ferdani, Riccardo ; Shokeen, Monica ; Anderson, Carolyn J
  • Description: Integrin α β (also called very late antigen-4 or VLA-4) plays an important role in tumor growth, angiogenesis and metastasis, and there has been increasing interest in targeting this receptor for cancer imaging and therapy. In this study, we conjugated a peptidomimetic ligand known to have good binding affinity for α β integrin to a cross-bridged macrocyclic chelator with a methane phosphonic acid pendant arm, CB-TE1A1P. CB-TE1A1P-LLP2A was labeled with Cu under mild conditions in high specific activity, in contrast to conjugates based on the “gold standard” di-acid cross-bridged chelator, CB-TE2A, which require high temperatures for efficient radiolabeling. Saturation binding assays demonstrated that Cu-CB-TE1A1P-LLP2A had comparable binding affinity (1.2 nM vs 1.6 nM) but more binding sites (B = 471 fmol/mg) in B16F10 melanoma tumor cells than Cu-CB-TE2A-LLP2A (B = 304 fmol/mg, < 0.03). In biodistribution studies, Cu-CB-TE1A1P-LLP2A had less renal retention but higher uptake in tumor (11.4 ± 2.3 %ID/g versus 3.1 ± 0.6 %ID/g, < 0.001) and other receptor-rich tissues compared to Cu-CB-TE2A-LLP2A. At 2 h post-injection, Cu-CB-TE1A1P-LLP2A also had significantly higher tumor:blood and tumor:muscle ratios than Cu-CB-TE2A-LLP2A (CB-TE1A1P = 19.5 ± 3.0 and 13.0 ± 1.4, respectively, CB-TE2A = 4.2 ± 1.4 and 5.5 ± 0.9, respectively, < 0.001). These data demonstrate that Cu-CB-TE1A1P-LLP2A is an excellent PET radiopharmaceutical for the imaging of α β positive tumors and also has potential for imaging other α β positive cells such as those of the pre-metastatic niche.
  • Is Part Of: Nuclear Medicine and Biology, February 2013, Vol.40(2), pp.245-251
  • Identifier: ISSN: 0969-8051 ; E-ISSN: 1872-9614 ; DOI: 10.1016/j.nucmedbio.2012.10.010
  • Subjects: Copper-64 ; Vla-4 ; Pet Imaging ; Medicine ; Biology ; Physics
  • Language: English

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