(99m) Tc Labeling Of Bombesin & ~ (177) Lu Labeled Rgd Peptide Radiopharmaceuticals

In this study, the bombesin (BN) and RGD (Arg-Gly-Asp) peptides were labeled with ^99mTc and ¹⁷⁷Lu, respectively, for tumor molecular imaging. We evaluated the impact of coligands and bifunctional chelators (BFCs) on the chemical and biological properties as well as pharmacokinetics of these radiotracers.We attempted ^99mTc-labeled bombesin analogue BN(7-14)NH₂ (HYNIC-β-Ala-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH₂) for imaging of colon cancer. A ternary ligands system was used in the ^99mTc labeling of HYNIC-BN(7-14)NH₂, using tricine (Tris(hydroxymethyl)methylglycine) and water-soluble TPPTS (trisodium triphenyl-phosphine-3,3',3"-trisulfonate), IsoNIC (isonicotinic acid), and PDA (2,5-pyridine-dicarboxylicacid) as coligands. These radiotracers ^99mTc(HYNIC-BN(7-14)NH₂)(tricine) (L)](L=TPPTS/IsoNIC/PDA) showed excellent labeling yield and in vitro stability. It was found that three coligands had significant impact on the properties of raiotracers. Among the three radiotracers, [^99mTc(HYNIC-BN(7-14)NH₂)(tricine)(TPPTS)] had the best hydrophilicity, so that it was excreted fast from kidneys, minimizing radioactivity accumulation in intestine and stomach. The clear images of [^99mTc(HYNIC-BN(7-14)NH₂) (tricine)(TPPTS)] in nude mice bearing HT29 human colon cancer xenografts were obtained at 1 h and 4 h postinjection. [^99mTc(HYNIC-BN(7-14)NH₂)(tricine)(TPPTS)] is a promising candidate for diagnosis of colon cancer.We chose different BFCs to prepared ¹⁷⁷Lu-labeled RGD dimmer, DTPA-Bz-E[c(RGDfK)]₂ (a), DOTA-E[c(RGDfK)]₂ (b), DOTA-Bz-E[c(RGDfK)]₂ (c), and evaluated their in vitro and in vivo characteristics. The radiolabeling yield of three preparations was more than 95%, with radiochemical purity (RCP) was more than 99% after purification. Receptor binding experiments were performed on U87MG human glioma cells for three compounds, with the IC₅₀ values were 3.23±0.78 nM (a), 2.35±0.75 nM (b) and 5.88±0.35 nM (c), respectively. There was no significant difference on integrin a_vβ₃ binding. The stability of three radiotrcers in saline and FBS solution was excellent with RCP > 95% during 24 h after labeling. There was no significant difference in Log P_o/w values of three radiotracers within the experimental error, which is consistent with their similarity in HPLC retention time. In general, all three radiotracers have very similar biodistribution patterns despite their difference in the ¹⁷⁷Lu chelates with respect to the molecular charge, chelator framework and donor atoms. The selective images of U87MG xenografted tumors were obtained at 4 h postinjection for ¹⁷⁷Lu-DOTA-Bz-E[C(RGDFK)]₂. The current study validates the feasibility of ¹⁷⁷Lu-labeled RGD dimmer for the therapy of integrin a_vβ₃-positive tumors.