Utilization of a novel electrochemical ⁹⁰Sr/⁹⁰Y generator for the preparation of ⁹⁰Y-labeled RGD peptide dimer in clinically relevant dose

Abstract

The work reported in this paper provides a systematic study towards the development of an optimized strategy for preparation of a clinically relevant dosefor in vivo targeted therapy utilizing 90 Y obtained from a novel electrochemical 90 Sr/ 90 Y generator. The performance of the generator was evaluated to ensure its suitability for providing 90 Y in adequate quantity and purity required for formulation of clinically relevant dose for PRRT. 90 Y-DOTA-(RGD) 2 was synthesized in high yield (86.2 ± 2.5%) and radiochemical purity (98.4 ± 0.5%) using clinically relevant dose (∼3.8 GBq) of 90 Y. In vitro stability studies revealed that the radiolabeled conjugate retained its radiochemical purity in normal saline and human serum. Preliminary biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors showed that the preparation exhibited significant tumor uptake (5.30 ± 0.78% of injected activity at 30 min post-injection) with good tumor to background ratio. The optimized radiolabeling protocol seems to be an attractive strategy which is largely viewed as a springboard to realize scope of developing 90 Y labeled cyclic RGD peptides for targeted therapy of tumors overexpressing integrin-3 receptors.

Peptide Receptor Radionuclide Therapy: An Overview

“…The authors reported a similar observation with the same RGD peptide derivative labeled with 90 Y. 212 Multimerization of the RGD motif significantly improved the tumor uptake as well as retention, but at the same time resulted in increased uptake in nontarget organs, mainly the liver, intestine, lung, and kidney. 187,191,[194][195][196][202][203][204][205][206] As a result, no significant improvement in tumor/kidney or tumor/liver could be observed by changing the targeting biomolecule from dimer to tetramer.…”

“…In the last couple of years, a few reports have described the use of tumor-targeting properties of radiolabeled RGD peptides beyond diagnostic applications and therapy monitoring to targeted tumor therapy using therapeutic radionuclides, which primarily include 90 Y and 177 Lu. [207][208][209][210][211][212] Figure 7 shows the structures of mono-, di-, and tetrameric RGD peptide derivatives, which could be used for radiolabeling with 90 have recently reported the preperation and biological evaluation of 177 Lu-labeled DOTA-E[c(RGDfK)] 2 in BALB/c mice bearing U87MG human glioma xenografts. 209,210 The radiotracer showed specific accumulation in the tumor.…”

Smart YPO4:Er–Yb Nanophosphor for Optical Heating, Hyperthermia, Security Ink, Cancer Endoradiotherapy, and Uranyl Recovery

“…Yttrium-90 used in the present study was sourced from a ∼ 4 GBq 90 Sr/ 90 Y generator system developed based on electrochemical separation of daughter 90 Y from its equilibrium mixture with parent 90 Sr. The detailed procedure of the electrochemical separation and purification of 90 Y has been reported earlier. − Yttrium-90 activity was finally obtained as 90 YCl 3 in 0.01 M ultrapure HCl. Assay of 90 Y activity was carried out using a liquid scintillation counter.…”

Electrochemical Separation: Promises, Opportunities, and Challenges To Develop Next-Generation Radionuclide Generators To Meet Clinical Demands

“…51 Yttrium-90 obtained from the generator was used for radiolabeling various BFCs, peptides, and other biological molecules with satisfactory radiolabeling yields. 51 remained consistently good over this period of 2 years. Therefore, it can be expected that 90 Y can be "milked" from this generator virtually for an indefinite period of time.…”

“…The electrochemical 90 Sr/ 90 Y generator was scaled up to 4.44 GBq (120 mCi) activity level, and its performance was evaluated for a period of 2 years . Yttrium-90 obtained from the generator was used for radiolabeling various BFCs, peptides, and other biological molecules with satisfactory radiolabeling yields. − The performance of the generator remained consistently good over this period of 2 years. Therefore, it can be expected that 90 Y can be “milked” from this generator virtually for an indefinite period of time.…”