Journal Article

Development of probes for radiotheranostics with albumin binding moiety to increase the therapeutic effects of astatine-211 (211At)

Fuchigami, Takeshi, Kinuya, Seigo, Kitamura, Yoji, Ogawa, Kazuma, Munekane, Masayuki, Mishiro, Kenji, Echigo, Hiroaki, Wakabayashi, Hiroshi, Takahashi, Kazuhiro, Washiyama, Kohshin

2024

Overview

Purpose We have developed probes for multiradionuclides radiotheranostics using RGD peptide ([ 67 Ga]Ga-DOTA-c[RGDf(4-I)K] ([ 67 Ga] 1 ) and Ga-DOTA-[ 211 At]c[RGDf(4-At)K] ([ 211 At] 2 )) for clinical applications. The introduction of an albumin binding moiety (ABM), such as 4-(4-iodophenyl)-butyric acid (IPBA), that has high affinity with the blood albumin and prolongs the circulation half-life can improve the pharmacokinetics of drugs. To perform more effective targeted alpha therapy (TAT), we designed and synthesized Ga-DOTA-K([ 211 At]APBA)-c(RGDfK) ([ 211 At] 5 ) with 4-(4-astatophenyl)-butyric acid (APBA), which has an astato group instead of an iodo group in IPBA. We evaluated whether APBA functions as ABM and [ 211 At] 5 is effective for TAT. In addition, we prepared 67 Ga-labeled RGD peptide without ABM, [ 67 Ga]Ga-DOTA-K-c(RGDfK) ([ 67 Ga] 3 ), and 125 I-labeled RGD peptide with ABM, Ga-DOTA-K([ 125 I]IPBA)-c(RGDfK) ([ 125 I] 4 ), to compare with [ 211 At] 5 . Methods Biodistribution experiments of [ 67 Ga] 3 without ABM, [ 125 I] 4 and [ 211 At] 5 with ABM were conducted in normal mice and U-87 MG tumor-bearing mice. In addition, two doses of [ 211 At] 5 (370 or 925 kBq) were administered to U-87 MG tumor-bearing mice to confirm the therapeutic effects. Results The blood retention of [ 125 I] 4 and [ 211 At] 5 was remarkably increased compared to [ 67 Ga] 3 . Also, [ 125 I] 4 and [ 211 At] 5 showed similar biodistribution and significantly greater tumor accumulation and retention compared to [ 67 Ga] 3 . In addition, [ 211 At] 5 inhibited tumor growth in a dose-dependent manner. Conclusion The functionality of APBA as ABM like IPBA, and the usefulness of [ 211 At] 5 as the radionuclide therapy agent for TAT was revealed.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Albumin / Albumins / Astatine / Binding / Biodistribution / Blood circulation / Butyric acid / Cardiology / Gallium isotopes / Imaging / Iodine 125 / Medicine / Medicine & Public Health / Nuclear Medicine / Oncology / Original Article / Orthopedics / Peptides / Pharmacokinetics / Probes / Radiation therapy / Radioisotopes / Radiology / Tumors