Synthesis, biodistribution and effects of farnesyltransferase inhibitor therapy on tumour uptake in mice of 99mTc labelled epidermal growth factor.
OBJECTIVE: The goal of this study was to develop a 99mTc labelled human epidermal growth factor (hEGF) for the in-vivo prediction of cancer cell response to farnesyltransferase inhibitor (FTI) therapy. This is based on the observation that internalization of EGF receptors is inhibited by FTIs. METH...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2005
|
| _version_ | 1826300631482105856 |
|---|---|
| author | Cornelissen, B Kersemans, V Burvenich, I Oltenfreiter, R Vanderheyden, J Boerman, O Vandewiele, C Slegers, G |
| author_facet | Cornelissen, B Kersemans, V Burvenich, I Oltenfreiter, R Vanderheyden, J Boerman, O Vandewiele, C Slegers, G |
| author_sort | Cornelissen, B |
| collection | OXFORD |
| description | OBJECTIVE: The goal of this study was to develop a 99mTc labelled human epidermal growth factor (hEGF) for the in-vivo prediction of cancer cell response to farnesyltransferase inhibitor (FTI) therapy. This is based on the observation that internalization of EGF receptors is inhibited by FTIs. METHODS: We describe the radiolabelling of 99mTc-hEGF using the hydrazinonicotinamide (HYNIC) linker. Binding characteristics of 99mTc-HYNIC-hEGF to the EGF receptor are explored using an in-vitro binding assay. Biodistribution data of the compound in mice and tumour uptake in LoVo tumour bearing athymic mice before and after farnesyltransferase inhibitor therapy are presented. RESULTS: No colloid formation was observed. Binding parameters and LoVo tumour uptake of 99mTc-HYNIC-hEGF did not differ significantly from directly labelled 123I-hEGF values. However, the biodistribution data of the 99mTc-HYNIC-hEGF showed higher uptake in liver and intestines and decreased stomach uptake compared to its 123I analogue. Eight hours after farnesyltransferase inhibitor therapy with R115777, LoVo tumour uptake of 99mTc-HYNIC-hEGF decreased significantly, as shown using planar gamma scintigraphy (the ratio tumour vs. thigh dropped from 2.54+/-0.83 to 0.99+/-0.18). These data confirm the results obtained using 123I-hEGF. CONCLUSION: These data suggest that 99mTc-HYNIC-hEGF is a promising and selective new radiotracer for in-vivo monitoring of the EGF receptor with SPECT. Moreover, 99mTc-HYNIC-hEGF is a possible tool for early therapy response prediction of farnesyltransferase inhibitors. |
| first_indexed | 2024-03-07T05:20:07Z |
| format | Journal article |
| id | oxford-uuid:de98adcb-c323-4b41-b05c-43af0de1300a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:20:07Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:de98adcb-c323-4b41-b05c-43af0de1300a2022-03-27T09:33:22ZSynthesis, biodistribution and effects of farnesyltransferase inhibitor therapy on tumour uptake in mice of 99mTc labelled epidermal growth factor.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:de98adcb-c323-4b41-b05c-43af0de1300aEnglishSymplectic Elements at Oxford2005Cornelissen, BKersemans, VBurvenich, IOltenfreiter, RVanderheyden, JBoerman, OVandewiele, CSlegers, G OBJECTIVE: The goal of this study was to develop a 99mTc labelled human epidermal growth factor (hEGF) for the in-vivo prediction of cancer cell response to farnesyltransferase inhibitor (FTI) therapy. This is based on the observation that internalization of EGF receptors is inhibited by FTIs. METHODS: We describe the radiolabelling of 99mTc-hEGF using the hydrazinonicotinamide (HYNIC) linker. Binding characteristics of 99mTc-HYNIC-hEGF to the EGF receptor are explored using an in-vitro binding assay. Biodistribution data of the compound in mice and tumour uptake in LoVo tumour bearing athymic mice before and after farnesyltransferase inhibitor therapy are presented. RESULTS: No colloid formation was observed. Binding parameters and LoVo tumour uptake of 99mTc-HYNIC-hEGF did not differ significantly from directly labelled 123I-hEGF values. However, the biodistribution data of the 99mTc-HYNIC-hEGF showed higher uptake in liver and intestines and decreased stomach uptake compared to its 123I analogue. Eight hours after farnesyltransferase inhibitor therapy with R115777, LoVo tumour uptake of 99mTc-HYNIC-hEGF decreased significantly, as shown using planar gamma scintigraphy (the ratio tumour vs. thigh dropped from 2.54+/-0.83 to 0.99+/-0.18). These data confirm the results obtained using 123I-hEGF. CONCLUSION: These data suggest that 99mTc-HYNIC-hEGF is a promising and selective new radiotracer for in-vivo monitoring of the EGF receptor with SPECT. Moreover, 99mTc-HYNIC-hEGF is a possible tool for early therapy response prediction of farnesyltransferase inhibitors. |
| spellingShingle | Cornelissen, B Kersemans, V Burvenich, I Oltenfreiter, R Vanderheyden, J Boerman, O Vandewiele, C Slegers, G Synthesis, biodistribution and effects of farnesyltransferase inhibitor therapy on tumour uptake in mice of 99mTc labelled epidermal growth factor. |
| title | Synthesis, biodistribution and effects of farnesyltransferase inhibitor therapy on tumour uptake in mice of 99mTc labelled epidermal growth factor. |
| title_full | Synthesis, biodistribution and effects of farnesyltransferase inhibitor therapy on tumour uptake in mice of 99mTc labelled epidermal growth factor. |
| title_fullStr | Synthesis, biodistribution and effects of farnesyltransferase inhibitor therapy on tumour uptake in mice of 99mTc labelled epidermal growth factor. |
| title_full_unstemmed | Synthesis, biodistribution and effects of farnesyltransferase inhibitor therapy on tumour uptake in mice of 99mTc labelled epidermal growth factor. |
| title_short | Synthesis, biodistribution and effects of farnesyltransferase inhibitor therapy on tumour uptake in mice of 99mTc labelled epidermal growth factor. |
| title_sort | synthesis biodistribution and effects of farnesyltransferase inhibitor therapy on tumour uptake in mice of 99mtc labelled epidermal growth factor |
| work_keys_str_mv | AT cornelissenb synthesisbiodistributionandeffectsoffarnesyltransferaseinhibitortherapyontumouruptakeinmiceof99mtclabelledepidermalgrowthfactor AT kersemansv synthesisbiodistributionandeffectsoffarnesyltransferaseinhibitortherapyontumouruptakeinmiceof99mtclabelledepidermalgrowthfactor AT burvenichi synthesisbiodistributionandeffectsoffarnesyltransferaseinhibitortherapyontumouruptakeinmiceof99mtclabelledepidermalgrowthfactor AT oltenfreiterr synthesisbiodistributionandeffectsoffarnesyltransferaseinhibitortherapyontumouruptakeinmiceof99mtclabelledepidermalgrowthfactor AT vanderheydenj synthesisbiodistributionandeffectsoffarnesyltransferaseinhibitortherapyontumouruptakeinmiceof99mtclabelledepidermalgrowthfactor AT boermano synthesisbiodistributionandeffectsoffarnesyltransferaseinhibitortherapyontumouruptakeinmiceof99mtclabelledepidermalgrowthfactor AT vandewielec synthesisbiodistributionandeffectsoffarnesyltransferaseinhibitortherapyontumouruptakeinmiceof99mtclabelledepidermalgrowthfactor AT slegersg synthesisbiodistributionandeffectsoffarnesyltransferaseinhibitortherapyontumouruptakeinmiceof99mtclabelledepidermalgrowthfactor |