Site-Specific Radioiodination of HER2-Targeting Affibody Molecules using 4-Iodophenethylmaleimide Decreases Renal Uptake of Radioactivity
(2015) In ChemistryOpen 4(2). p.174-182- Abstract
Affibody molecules are small scaffold-based affinity proteins with promising properties as probes for radionuclide-based molecular imaging. However, a high reabsorption of radiolabeled Affibody molecules in kidneys is an issue. We have shown that the use of (125)I-3-iodo-((4-hydroxyphenyl)ethyl)maleimide (IHPEM) for site-specific labeling of cysteine-containing Affibody molecules provides high tumor uptake but low radioactivity retention in kidneys. We hypothesized that the use of 4-iodophenethylmaleimide (IPEM) would further reduce renal retention of radioactivity because of higher lipophilicity of radiometabolites. An anti-human epidermal growth factor receptor type 2 (HER2) Affibody molecule (ZHER2:2395) was labeled using (125)I-IPEM... (More)
Affibody molecules are small scaffold-based affinity proteins with promising properties as probes for radionuclide-based molecular imaging. However, a high reabsorption of radiolabeled Affibody molecules in kidneys is an issue. We have shown that the use of (125)I-3-iodo-((4-hydroxyphenyl)ethyl)maleimide (IHPEM) for site-specific labeling of cysteine-containing Affibody molecules provides high tumor uptake but low radioactivity retention in kidneys. We hypothesized that the use of 4-iodophenethylmaleimide (IPEM) would further reduce renal retention of radioactivity because of higher lipophilicity of radiometabolites. An anti-human epidermal growth factor receptor type 2 (HER2) Affibody molecule (ZHER2:2395) was labeled using (125)I-IPEM with an overall yield of 45±3 %. (125)I-IPEM-ZHER2:2395 bound specifically to HER2-expressing human ovarian carcinoma cells (SKOV-3 cell line). In NMRI mice, the renal uptake of (125)I-IPEM-ZHER2:2395 (24±2 and 5.7±0.3 % IA g(-1)at 1 and 4 h after injection, respectively) was significantly lower than uptake of (125)I-IHPEM-ZHER2:2395 (50±8 and 12±2 % IA g(-1)at 1 and 4 h after injection, respectively). In conclusion, the use of a more lipophilic linker for the radioiodination of Affibody molecules reduces renal radioactivity.
(Less)
- author
- Strand, Joanna LU ; Nordeman, Patrik ; Honarvar, Hadis ; Altai, Mohamed LU ; Orlova, Anna ; Larhed, Mats and Tolmachev, Vladimir
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- in
- ChemistryOpen
- volume
- 4
- issue
- 2
- pages
- 174 - 182
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85027934622
- pmid:25969816
- ISSN
- 2191-1363
- DOI
- 10.1002/open.201402097
- language
- English
- LU publication?
- no
- id
- 4ca20cf4-68a2-4fac-9b66-73ff2f2686cf
- date added to LUP
- 2022-11-15 10:57:27
- date last changed
- 2024-02-01 14:23:57
@article{4ca20cf4-68a2-4fac-9b66-73ff2f2686cf, abstract = {{<p>Affibody molecules are small scaffold-based affinity proteins with promising properties as probes for radionuclide-based molecular imaging. However, a high reabsorption of radiolabeled Affibody molecules in kidneys is an issue. We have shown that the use of (125)I-3-iodo-((4-hydroxyphenyl)ethyl)maleimide (IHPEM) for site-specific labeling of cysteine-containing Affibody molecules provides high tumor uptake but low radioactivity retention in kidneys. We hypothesized that the use of 4-iodophenethylmaleimide (IPEM) would further reduce renal retention of radioactivity because of higher lipophilicity of radiometabolites. An anti-human epidermal growth factor receptor type 2 (HER2) Affibody molecule (ZHER2:2395) was labeled using (125)I-IPEM with an overall yield of 45±3 %. (125)I-IPEM-ZHER2:2395 bound specifically to HER2-expressing human ovarian carcinoma cells (SKOV-3 cell line). In NMRI mice, the renal uptake of (125)I-IPEM-ZHER2:2395 (24±2 and 5.7±0.3 % IA g(-1)at 1 and 4 h after injection, respectively) was significantly lower than uptake of (125)I-IHPEM-ZHER2:2395 (50±8 and 12±2 % IA g(-1)at 1 and 4 h after injection, respectively). In conclusion, the use of a more lipophilic linker for the radioiodination of Affibody molecules reduces renal radioactivity. </p>}}, author = {{Strand, Joanna and Nordeman, Patrik and Honarvar, Hadis and Altai, Mohamed and Orlova, Anna and Larhed, Mats and Tolmachev, Vladimir}}, issn = {{2191-1363}}, language = {{eng}}, number = {{2}}, pages = {{174--182}}, publisher = {{John Wiley & Sons Inc.}}, series = {{ChemistryOpen}}, title = {{Site-Specific Radioiodination of HER2-Targeting Affibody Molecules using 4-Iodophenethylmaleimide Decreases Renal Uptake of Radioactivity}}, url = {{http://dx.doi.org/10.1002/open.201402097}}, doi = {{10.1002/open.201402097}}, volume = {{4}}, year = {{2015}}, }