| 1. |
|
|
| 2. |
- Zhao, Q, et al.
(author)
-
Conjugate chemistry, iodination and cellular binding of mEGF-dextran-tyrosine: preclinical tests in preparation for clinicaltrials
- 1998
-
In: International Journal of Molecular Medicine. - : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 1:4, s. 693-702
-
Journal article (peer-reviewed)abstract
- A conjugate with specific binding to the epidermal growth factor receptor, EGFR, and of interest for clinical tests was prepared using mouse epidermal growth factor, mEGF, and dextran. The mEGF was first coupled to dextran by reductive amination in which the free amino group on the N-terminal of mEGF was reacted with the aldehyde group on the reductive end of the dextran chain. The end-end coupled intermediate was further activated by the cyanopyridinium agent CDAP and tyrosines introduced to the dextran part of the conjugate. The mEGF-dextran-tyrosine conjugate was, with high efficiency, iodinated with the chloramine-T method. Approximately 25-35% of the radioactivity could be removed from the conjugate after exposure to protease K while 65-75% of the radioactivity could be removed after exposure to dextranase. Thus, the largest amount of the iodine was on the dextran part of the conjugate. The iodinated mEGF-dextran-tyrosine had EGFR specific binding since the binding to an EGFR rich human glioma cell line could be displaced by an excess of non-radioactive mEGF. The conjugate was to a large extent internalized in these cells and the administrated radioactivity was thereby retained inside the cells for at least up to 50 h.
|
|
| 3. |
- Bohl Kullberg, E, et al.
(author)
-
Introductory experiments on ligand liposomes as delivery agents for boronneutron capture therapy
- 2003
-
In: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 23:2, s. 461-467
-
Journal article (peer-reviewed)abstract
- Liposomes are, when coupled to receptor ligands, candidates for receptor mediated delivery of boron for tumour therapy since they have capacity to deliver large amounts of boron per receptor interaction. With EGF-liposomes we present a pegylated ligand liposome delivery vehicle, containing water soluble boronated phenanthridine, WSP1, or water soluble boronated acridine, WSA1, for EGFR targeting. In the case of WSA1 a ligand dependent uptake was obtained and the boron uptake was as good as if free WSA1 was given. No ligand dependent boron uptake was seen for WSP1 containing liposomes. Thus, WSA1 is a candidate for further studies. Approximately 10(5) boron atoms were in each liposome. A critical assessment indicates that after optimization up to 10(6) boron atoms can be loaded. Since it is known that, for therapeutic effect, approximately 10(8)-10(9) boron atoms are needed in a single tumour cell it is realized that 10(2)-10(3) receptor interactions are needed to meet the demand. Tests applying cultured glioma cells indicate, without optimization of the delivery conditions, a boron uptake in the ppm range, which is necessary for successful BNCT. Thus, it seems possible to kill micro-invasive tumour cells with targeted liposomes if the delivery conditions are optimal.
|
|
| 4. |
- Carlsson, Jörgen, et al.
(author)
-
HER2 expression in breast cancer primary tumours and corresponding metastases : Original data and literature review
- 2004
-
In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 90:12, s. 2344-2348
-
Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate whether the HER2 expression in breast cancer is retained in metastases. The HER2 expression in primary tumours and the corresponding lymph node metastases were evaluated in parallel samples from 47 patients. The HercepTest was used for immunohistochemical analyses of HER2 overexpression in all cases. CISH/FISH was used for analysis of gene amplification in some cases. HER2 overexpression (HER2-scores 2+ or 3+) was found in 55% of both the primary tumours and of the lymph node metastases. There were only small changes in the HER2-scores; six from 1+ to 0 and one from 3+ to 2+ when the metastases were compared to the corresponding primary tumours. However, there were no cases with drastic changes in HER2 expression between the primary tumours and the corresponding lymph node metastases. The literature was reviewed for similar investigations, and it is concluded that breast cancer lymph node metastases generally overexpress HER2 to the same extent as the corresponding primary tumours. This also seems to be the case when distant metastases are considered. It has been noted that not all patients with HER2 overexpression respond to HER2-targeted Trastuzumab treatment. The stability in HER2 expression is encouraging for efforts to develop complementary forms of therapy, for example, therapy with radionuclide-labelled Trastuzumab.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Orlova, Anna, et al.
(author)
-
Tumor imaging using a picomolar affinity HER2 binding affibody molecule
- 2006
-
In: Cancer Research. - 0008-5472 .- 1538-7445. ; 66:8, s. 4339-48
-
Journal article (peer-reviewed)abstract
- The detection of cell-bound proteins that are produced due to aberrant gene expression in malignant tumors can provide important diagnostic information influencing patient management. The use of small radiolabeled targeting proteins would enable high-contrast radionuclide imaging of cancers expressing such antigens if adequate binding affinity and specificity could be provided. Here, we describe a HER2-specific 6 kDa Affibody molecule (hereinafter denoted Affibody molecule) with 22 pmol/L affinity that can be used for the visualization of HER2 expression in tumors in vivo using gamma camera. A library for affinity maturation was constructed by re-randomization of relevant positions identified after the alignment of first-generation variants of nanomolar affinity (50 nmol/L). One selected Affibody molecule, Z(HER2:342) showed a >2,200-fold increase in affinity achieved through a single-library affinity maturation step. When radioiodinated, the affinity-matured Affibody molecule showed clear, high-contrast visualization of HER2-expressing xenografts in mice as early as 6 hours post-injection. The tumor uptake at 4 hours post-injection was improved 4-fold (due to increased affinity) with 9% of the injected dose per gram of tissue in the tumor. Affibody molecules represent a new class of affinity molecules that can provide small sized, high affinity cancer-specific ligands, which may be well suited for tumor imaging.
|
|
| 8. |
|
|
| 9. |
- Sjöström, A, et al.
(author)
-
Direct astatination of a peptide, human epidermal growth factor, using nido-carborane as a prosthetic group
- 2000
-
In: Nuclear medicine communications. - 0143-3636 .- 1473-5628. ; 21:6, s. 594-
-
Review (other academic/artistic)abstract
- Purpose The aim of the study was to evaluate direct astatine labelling of proteins with the use of nido-carborane as prosthetic group for attachments of astatine. Methods: Human epidermal growth factor, hEGF, was conjugated to 7-(3-amino-propyl)-7,8-dicarbanido-undecaborate (-), ANC, using two different conjugation methods, glutaraldehyde crosslinking and coupling via Traut's reagent. The hEGF-ANC conjugates were astatine labelled using the Chloramine-T method. The stability of the labelled compounds was tested by incubation at 37°C. Results: The conjugates were astatinated using the Chloramine-T method in high yield. The best labelling yields were obtained by the glutaraldehyde conjugate with an average yield of 70.5±2.2%. In vitro stability tests indicated that the introduced label was as stable as hEGF labelled with astatobenzoate. Conclusion: Conjugation of nido-carboranes to peptides creates binding sites for direct astatine labelling that can be performed in mild conditions (p 7.2) with high labelling yields.
|
|
| 10. |
- Sjöström, A., et al.
(author)
-
Direct astatination of a tumour-binding protein, human Epidermal Growth Factor, using nido-carborane as a prosthetic group
- 2003
-
In: Journal of Radioanalytical and Nuclear Chemistry. - 0236-5731 .- 1588-2780. ; 256:2, s. 191-197
-
Journal article (peer-reviewed)abstract
- We have investigated a method for direct astatine labeling of proteins. Binding sites for astatine were created by coupling of a nido-carborane derivative to a protein, the human epidermal growth factor (hEGF), using two different conjugation methods - by glutaraldehyde cross-linking or by introduction of sulfohydryl groups by Traut's reagent with subsequent linking of ANC-1 with m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester. The conjugates were astatinated using the Chloramine-T method in high yield. The best labeling was obtained by the glutaraldehyde conjugate with an average yield of 68±9%. In vitro stability tests indicated that the glutaraldehyde conjugated label was as stable as hEGF labeled with astatobenzoate.
|
|
