Next Article in Journal
Formulation Strategies for Folate-Targeted Liposomes and Their Biomedical Applications
Next Article in Special Issue
Therapeutic Potential of 47Sc in Comparison to 177Lu and 90Y: Preclinical Investigations
Previous Article in Journal
Retinol-Containing Graft Copolymers for Delivery of Skin-Curing Agents
Previous Article in Special Issue
Beyond the Barrier: Targeted Radionuclide Therapy in Brain Tumors and Metastases
Open AccessArticle

Evaluation of Tumor-Targeting Properties of an Antagonistic Bombesin Analogue RM26 Conjugated with a Non-Residualizing Radioiodine Label Comparison with a Radiometal-Labelled Counterpart

1
Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden
2
Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala, Sweden
3
Science for Life Laboratory, Uppsala University, SE-750 03 Uppsala, Sweden
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(8), 380; https://doi.org/10.3390/pharmaceutics11080380
Received: 13 June 2019 / Revised: 16 July 2019 / Accepted: 24 July 2019 / Published: 2 August 2019
(This article belongs to the Special Issue Targeted Radionuclide Tumor Therapy)
  |  
PDF [4390 KB, uploaded 2 August 2019]
  |  

Abstract

Radiolabelled antagonistic bombesin analogues are successfully used for targeting of gastrin-releasing peptide receptors (GRPR) that are overexpressed in prostate cancer. Internalization of antagonistic bombesin analogues is slow. We hypothesized that the use of a non-residualizing radioiodine label might not affect the tumour uptake but would reduce the retention in normal organs, where radiopharmaceutical would be internalized. To test this hypothesis, tyrosine was conjugated via diethylene glycol linker to N-terminus of an antagonistic bombesin analogue RM26 to form Tyr-PEG2-RM26. [111In]In-DOTA-PEG2-RM26 was used as a control with a residualizing label. Tyr-PEG2-RM26 was labelled with 125I with 95% radiochemical purity and retained binding specificity to GRPR. The IC50 values for Tyr-PEG2-RM26 and DOTA-PEG2-RM26 were 1.7 ± 0.3 nM and 3.3 ± 0.5 nM, respectively. The cellular processing of [125I]I-Tyr-PEG2-RM26 by PC-3 cells showed unusually fast internalization. Biodistribution showed that uptake in pancreas and tumour was GRPR-specific for both radioconjugates. Blood clearance of [125I]I-Tyr-PEG2-RM26 was appreciably slower and activity accumulation in all organs was significantly higher than for [111In]In-DOTA-PEG2-RM26. Tumor uptake of [111In]In-DOTA-PEG2-RM26 was significantly higher than for [125I]I-Tyr-PEG2-RM26, resulting in higher tumour-to-organ ratio for [111In]In-DOTA-PEG2-RM26 at studied time points. Incorporation of amino acids with hydrophilic side-chains next to tyrosine might overcome the problems associated with the use of tyrosine as a prosthetic group for radioiodination. View Full-Text
Keywords: prostate cancer; bombesin antagonistic analogue; GRPR; RM26; tyrosine; PC-3 xenografts prostate cancer; bombesin antagonistic analogue; GRPR; RM26; tyrosine; PC-3 xenografts
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Oroujeni, M.; Abouzayed, A.; Lundmark, F.; Mitran, B.; Orlova, A.; Tolmachev, V.; Rosenström, U. Evaluation of Tumor-Targeting Properties of an Antagonistic Bombesin Analogue RM26 Conjugated with a Non-Residualizing Radioiodine Label Comparison with a Radiometal-Labelled Counterpart. Pharmaceutics 2019, 11, 380.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Pharmaceutics EISSN 1999-4923 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top