Kit-based preparation of [68Ga]Ga-P16-093 (PSMA-093) using different commercial 68Ge/68Ga generators

New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177)

“…10,11,16,20 As a close analog of [ 68 Ga]Ga-PSMA-11, 20,21 [ 68 Ga]Ga-P16-093 is also an excellent PSMA-targeting PET imaging agent, which is currently under phase II clinical trial for diagnosis and monitoring of patients with prostate cancer. [10][11][12][13]16,19,22 The stability constant of Ga(III)-HBED is excellent (logK d = 38.5); 23−25 however, the stability of the Lu(III)-HBED complex is much weaker (logK d = 21). 26 For the development of a radionuclide therapeutic agent, it is necessary to replace the chelating group, HBED-CC, to a different group with , 24 which leads to a variety of stable metal complexes.…”

“…Previously, we reported a PSMA targeting imaging agent, [ 68 Ga]­Ga-P16-093 ([ 68 Ga]­Ga-HBED-CC-Gly- O -(methylcarboxy)-Tyr-Phe-Lys-NH-CO-NH-Glu) (Figure ). ,,, As a close analog of [ 68 Ga]­Ga-PSMA-11, , [ 68 Ga]­Ga-P16-093 is also an excellent PSMA-targeting PET imaging agent, which is currently under phase II clinical trial for diagnosis and monitoring of patients with prostate cancer. − ,,, The stability constant of Ga­(III)-HBED is excellent (log K d = 38.5); − however, the stability of the Lu­(III)-HBED complex is much weaker (log K d = 21) . For the development of a radionuclide therapeutic agent, it is necessary to replace the chelating group, HBED-CC, to a different group with stronger chelating capacity for Lu­(III).…”

Lu-177-Labeled Hetero-Bivalent Agents Targeting PSMA and Bone Metastases for Radionuclide Therapy

“…These bivalent DOTA derivatives, combining the linker and PSMA binding groups (X = Glu-NH-CO-NH-Lys-Phe-O-carboxymethyl)-Tyr-in blue, Figure 2) from P16-093 with a bisphosphonate group for bone targeting, were prepared and evaluated. A minor difference in the chemical structures of [ 177 Ga]Ga-P16−093, was successfully prepared 37,38 and tested in humans. 39−41 A bisphosphonate ([ 68 Ga]Ga-P15-041) has been tested in humans for imaging bone metastasis.…”

“…A PSMA-targeting imaging agent, [ 68 Ga]­Ga-P16–093, was successfully prepared , and tested in humans. − A bisphosphonate ([ 68 Ga]­Ga-P15-041) has been tested in humans for imaging bone metastasis. ,, Using DOTA derivatives as the chelator and the same PSMA binding moiety and linker (Glu-NH-CO-NH-Lys-Phe- O -carboxymethyl)-Tyr- = X in blue) from the diagnostic agent, [ 68 Ga]­Ga-P16-093, [ 177 Lu]­Lu-P19-065 (Approach #1) and [ 177 Lu]­Lu-P17–087, [ 177 Lu]­Lu-P17-088 (Approach #2) were successfully transformed to radionuclide therapy agents. To develop hetero-bivalent agents, R = Gly-bisphosphonate was added for targeting bone metastasis, resulting in the formation of hetero-bivalent agents, [M]-P17-079 ([M]-1) and [M]-P17-081 ([M]-2) with [M] = [ 68 Ga/ 177 Lu].…”

“…Figure2. A PSMA-targeting imaging agent, [ 68 Ga]Ga-P16−093, was successfully prepared37,38 and tested in humans. 39−41 A bisphosphonate ([ 68 Ga]Ga-P15-041) has been tested in humans for imaging bone metastasis 25,26,42.…”