Synthesis, stabilization and formulation of [177Lu]Lu-AMBA, a systemic radiotherapeutic agent for Gastrin Releasing Peptide receptor positive tumors

In Vitro and in Vivo Characterization of Novel 18F-Labeled Bombesin Analogues for Targeting GRPR-Positive Tumors

“…A number of potent BBS analogues have been labeled with various radionuclides, such as 99 m Tc, 111 In, 90 Y, 64 Cu, 177 Lu, 68 Ga, or 18 F, for targeting GRPR-expressing cancer cells in both animal models and human subjects (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Among the available PET nuclides, 18 F has ideal characteristics for peptide receptor imaging studies in terms of its half-life (109.7 min) and low + energy (0.64 MeV) (26).…”

Preparation and evaluation of a single vial AMBA kit for 68Ga labeling with potential for imaging of GRP receptor-positive cancers

“…There are literature reports on the complete metabolism of 177 Lu-AMBA in animals [41] while there are no similar studies reported with 68 Ga-AMBA. A head to head comparison with 177 Lu-AMBA reported elsewhere [35,41] is not feasible due to the different isotopes used as well as the different amounts of activity used. Specificity towards the GRP receptor could be established by the high pancreatic uptake of 68 Ga-AMBA in normal Swiss mice which reduced on blocking with cold AMBA.…”

“…In order to ascertain the suitability of the standardized formulation to achieve' radiolabeling yields in excess of 95 % using 68 GaCl 3 eluted from the in-house generator, the optimized peptide solution was mixed with the chosen buffer formulation and the reaction was carried out at 90°C for 10 min after adding 1 mL of 68 GaCl 3 (*148-185 MBq in 0.1 mol L -1 HCl) from the 68 Ge/ 68 Ga generator system. There are previous reports on the use of radioprotectants during the preparation of 68 Ga and 177 Lu labeled AMBA as the methionine residue of the peptide has a tendency to get oxidised readily [28,35]. Hence, the amount of ascorbic acid required in the final formulation for irreversible binding of 68 Ga to the peptide was studied by adding varying amounts of ascorbic acid to the kit vial after performing 68 Ga labeling and determining the in vitro stability of 68 Ga-AMBA up to 2 h after preparation.…”

“…Recently, Asti et al have studied the influence of various chelators viz., DOTA, NOTA and NODAGA on the radiochemical properties of AMBA [33] and Liu et al have reported on the preparation and bioevaluation of 64 Cu and 18 F labeled NODAGA-AMBA [34]. Hence, while there are reports on the automated synthesis of 68 Ga-AMBA using the commercially available 68 Ge/ 68 Ga generators and the AMBA kits originally formulated for preparation of 177 Lu-AMBA [28,35], to the best of our knowledge, a straight-forward kit formulation strategy exclusively for radiolabeling with 68 Ga has not been reported elsewhere. In view of this premise, formulation of freeze-dried kits of AMBA for 68 Ga labeling is not only an interesting prospect, but is a potential step towards its possible clinical use.…”

In Vitro and In Vivo Evaluation of Melanin-Binding Decapeptide 4B4 Radiolabeled with 177Lu, 166Ho, and 153Sm Radiolanthanides for the Purpose of Targeted Radionuclide Therapy of Melanoma

“…The DO3A-CH 2 CO-chelator (often called the generic DOTA) binds to lanthanide metals and has been used as the chelator for 177 Lu-AMBA, a selective 177 Lu-labeled GRP-R agonist for systemic radiotherapy of prostate cancer. 20,21 This ligand is formally a heptadentate DO3A ligand, although it is possible for the carbonyl that is on the arm linking the DO3A moiety to the PEG linker to weakly bind to the radiolanthanide.…”