Abstract
Introduction: Click chemistry, particularly the Huisgen 1,3-dipolar cycloaddition of an alkyne with an azide, has quickly become popular for site-specific radiolabeling. Recently, strain-promoted click chemistries have been developed, eliminating the need for potentially toxic copper catalysts. This study presents radiolabeling of an αvβ6 integrin targeting peptide (A20FMDV2) via strain-promoted click using a fluorine-18 prosthetic group, and in vitro and in vivo evaluation. Methods: The radiotracer [18F]FBA-C6-ADIBON3-PEG7-A20FMDV2 (1) was prepared from [18F]FBA-C6-ADIBO (2) and N3-PEG7-A20FMDV2 (ethanol; 10min; 35-45°C). HPLC-purified and formulated radiotracer 1 was evaluated in vitro by cell binding (DX3puroβ6, αvβ6-positive; and DX3puro, αvβ6-negative control) and serum stability, and in vivo using PET/CT imaging and biodistribution studies in mice. Results: The radiotracer 1 was readily prepared and purified (from 2: 40±4min including HPLC, 11.9±3.2% decay corrected isolated radiochemical yield, >99% radiochemical purity, n=4) and displayed good stability (1h: >99%, saline; 94.6%, serum). Strong αvβ6-targeted binding was observed in vitro (DX3puroβ6 cells, 15min: 43.2% binding, >6:1 for DX3puroβ6:DX3puro). In the mouse model DX3puroβ6-tumor binding was low (1h: 0.47±0.28% ID/g, 4h: 0.14±0.09% ID/g) and clearing from the bloodstream was via the renal and hepatobiliary routes (urine: 167±84% ID/g at 1h, 10.3±4.8% ID/g at 4h; gall bladder: 95±33% ID/g at 1h, 63±11% ID/g at 4h). Conclusion: Copper-free, strain-promoted click chemistry is an attractive, straightforward approach to radiolabeling. Although the [18F]FBA-C6-ADBIO-based prosthetic group did not interfere with αvβ6-targeted binding in vitro, it did influence the pharmacokinetics, possibly due to its size and lipophilic nature.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 233-239 |
| Number of pages | 7 |
| Journal | Nuclear Medicine and Biology |
| Volume | 40 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2013 |
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Keywords
- Copper-free
- Cyclooctyne
- Diagnostic radionuclides
- Fluorine 18
- Positron
- Strain-promoted click
ASJC Scopus subject areas
- Cancer Research
- Molecular Medicine
- Radiology Nuclear Medicine and imaging
Cite this
Evaluation of an integrin αvβ6-specific peptide labeled with [18F]fluorine by copper-free, strain-promoted click chemistry. / Hausner, Sven H.; Carpenter, Richard D.; Bauer, Nadine; Sutcliffe, Julie.
In: Nuclear Medicine and Biology, Vol. 40, No. 2, 02.2013, p. 233-239.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evaluation of an integrin αvβ6-specific peptide labeled with [18F]fluorine by copper-free, strain-promoted click chemistry
AU - Hausner, Sven H.
AU - Carpenter, Richard D.
AU - Bauer, Nadine
AU - Sutcliffe, Julie
PY - 2013/2
Y1 - 2013/2
N2 - Introduction: Click chemistry, particularly the Huisgen 1,3-dipolar cycloaddition of an alkyne with an azide, has quickly become popular for site-specific radiolabeling. Recently, strain-promoted click chemistries have been developed, eliminating the need for potentially toxic copper catalysts. This study presents radiolabeling of an αvβ6 integrin targeting peptide (A20FMDV2) via strain-promoted click using a fluorine-18 prosthetic group, and in vitro and in vivo evaluation. Methods: The radiotracer [18F]FBA-C6-ADIBON3-PEG7-A20FMDV2 (1) was prepared from [18F]FBA-C6-ADIBO (2) and N3-PEG7-A20FMDV2 (ethanol; 10min; 35-45°C). HPLC-purified and formulated radiotracer 1 was evaluated in vitro by cell binding (DX3puroβ6, αvβ6-positive; and DX3puro, αvβ6-negative control) and serum stability, and in vivo using PET/CT imaging and biodistribution studies in mice. Results: The radiotracer 1 was readily prepared and purified (from 2: 40±4min including HPLC, 11.9±3.2% decay corrected isolated radiochemical yield, >99% radiochemical purity, n=4) and displayed good stability (1h: >99%, saline; 94.6%, serum). Strong αvβ6-targeted binding was observed in vitro (DX3puroβ6 cells, 15min: 43.2% binding, >6:1 for DX3puroβ6:DX3puro). In the mouse model DX3puroβ6-tumor binding was low (1h: 0.47±0.28% ID/g, 4h: 0.14±0.09% ID/g) and clearing from the bloodstream was via the renal and hepatobiliary routes (urine: 167±84% ID/g at 1h, 10.3±4.8% ID/g at 4h; gall bladder: 95±33% ID/g at 1h, 63±11% ID/g at 4h). Conclusion: Copper-free, strain-promoted click chemistry is an attractive, straightforward approach to radiolabeling. Although the [18F]FBA-C6-ADBIO-based prosthetic group did not interfere with αvβ6-targeted binding in vitro, it did influence the pharmacokinetics, possibly due to its size and lipophilic nature.
AB - Introduction: Click chemistry, particularly the Huisgen 1,3-dipolar cycloaddition of an alkyne with an azide, has quickly become popular for site-specific radiolabeling. Recently, strain-promoted click chemistries have been developed, eliminating the need for potentially toxic copper catalysts. This study presents radiolabeling of an αvβ6 integrin targeting peptide (A20FMDV2) via strain-promoted click using a fluorine-18 prosthetic group, and in vitro and in vivo evaluation. Methods: The radiotracer [18F]FBA-C6-ADIBON3-PEG7-A20FMDV2 (1) was prepared from [18F]FBA-C6-ADIBO (2) and N3-PEG7-A20FMDV2 (ethanol; 10min; 35-45°C). HPLC-purified and formulated radiotracer 1 was evaluated in vitro by cell binding (DX3puroβ6, αvβ6-positive; and DX3puro, αvβ6-negative control) and serum stability, and in vivo using PET/CT imaging and biodistribution studies in mice. Results: The radiotracer 1 was readily prepared and purified (from 2: 40±4min including HPLC, 11.9±3.2% decay corrected isolated radiochemical yield, >99% radiochemical purity, n=4) and displayed good stability (1h: >99%, saline; 94.6%, serum). Strong αvβ6-targeted binding was observed in vitro (DX3puroβ6 cells, 15min: 43.2% binding, >6:1 for DX3puroβ6:DX3puro). In the mouse model DX3puroβ6-tumor binding was low (1h: 0.47±0.28% ID/g, 4h: 0.14±0.09% ID/g) and clearing from the bloodstream was via the renal and hepatobiliary routes (urine: 167±84% ID/g at 1h, 10.3±4.8% ID/g at 4h; gall bladder: 95±33% ID/g at 1h, 63±11% ID/g at 4h). Conclusion: Copper-free, strain-promoted click chemistry is an attractive, straightforward approach to radiolabeling. Although the [18F]FBA-C6-ADBIO-based prosthetic group did not interfere with αvβ6-targeted binding in vitro, it did influence the pharmacokinetics, possibly due to its size and lipophilic nature.
KW - Copper-free
KW - Cyclooctyne
KW - Diagnostic radionuclides
KW - Fluorine 18
KW - Positron
KW - Strain-promoted click
UR - http://www.scopus.com/inward/record.url?scp=84872927513&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872927513&partnerID=8YFLogxK
U2 - 10.1016/j.nucmedbio.2012.10.007
DO - 10.1016/j.nucmedbio.2012.10.007
M3 - Article
C2 - 23265667
AN - SCOPUS:84872927513
VL - 40
SP - 233
EP - 239
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
SN - 0969-8051
IS - 2
ER -