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Karyon-CTT and Karyon Oy | Date: 2005-04-26

pharmaceutical preparations for the treatment of cancer; diagnostic preparations for clinical or medical laboratory use.

Karyon-CTT | Date: 2003-12-23

Pharmaceutical preparations for the treatment of cancer; diagnostic preparations for clinical or medical laboratory use.

Ujula T.,University of Turku | Huttunen M.,Karyon-CTT | Luoto P.,University of Turku | Perakyla H.,Karyon-CTT | And 4 more authors.
Bioconjugate Chemistry | Year: 2010

Biopanning of tumor cells was used in order to identify matrix metalloproteinase 9 (MMP-9) targeting peptides. The tumor cell targeting peptide (TCTP-1) and two modified versions thereof were evaluated as imaging agents for positron emission tomography (PET) using a rat melanoma xenograft model. For the PET imaging purposes, the 3 peptides were 1,4,7,10-tetraazacyclo-dodecane- N′,N″,N‴,N″″-tetraacetic acid (DOTA) conjugated and labeled with Gallium-68 (68Ga) and preliminarily evaluated: (1) cyclic 68Ga-DOTA-TCTP-1 with cystine bridge, (2) cyclic 68Ga-DOTA-lactam-TCTP-1 with a lactam bridge, and (3) linear 68Ga-DOTA-lin-TCTP-1. The whole-body distribution kinetics and tumor targeting of the intravenously administered 68Ga-DOTA-peptides were evaluated in vivo by PET and ex vivo by measuring the radioactivity of excised tissues. In addition, the in vivo stability of the radiolabeled peptides in rat plasma, tumor tissue, and urine was studied. All 68Ga-DOTA-peptides were cleared via the liver and kidneys, and approximately 44% of injected radioactivity was excreted in urine during 120 min after injection. Ex vivo biodistribution studies showed a tumor-to-muscle ratio of 5.5 ± 1.3 (mean ± SD) for 68Ga-DOTA-TCTP-1, 3.2 ± 0.2 for 68Ga-DOTA-lactam-TCTP-1, and 3.2 ± 0.6 for 68Ga-DOTA-lin-TCTP-1 at 120 min after injection. The 68Ga-DOTA-lactam-TCTP-1 peptide appeared to be the most stable in vivo. The fraction of intact 68Ga-DOTA-lactam-TCTP-1 in tumor was 59 ± 4.2% at 120 min after injection. The stability was moderate for 68Ga-DOTA-TCTP-1 and poor for 68Ga-DOTA-lin-TCTP-1. The possibility of imaging tumors that overexpress MMP-9, such as melanoma, by using radiolabeled TCTP peptides in PET imaging makes these peptides highly attractive for diagnostic and therapeutic applications. However, further modifications to improve the stability and affinity of the peptides are needed. © 2010 American Chemical Society.

Koivistoinen A.,Karyon-CTT | Ilonen I.I.K.,University of Helsinki | Punakivi K.,Karyon-CTT | Rasanen J.V.,University of Helsinki | And 4 more authors.
Clinical and Translational Oncology | Year: 2013

Aim: To identify linear peptide homing to non-small cell lung cancer (NSCLC) tumor cells using ex vivo phage display method. Materials and methods: Twenty-six clinical patient samples were used to identify linear homing peptide, which was exposed to NSCLC cell cultures and control cell lines to determine cell binding affinity and cell localization. Also, ex vivo biodistribution was analyzed using tumor-bearing mice. Results: The panning yielded peptide enrichment with a core motif A/SRXPXXX. Based on this, an amino acid sequence, ARRPKLD, was selected for characterization and named Thx-peptide. The in vitro binding properties of Thx-peptide demonstrated selectivity toward NSCLC. Internalization assays showed that Thx-Alexa and fluorescein conjugates were located in a subset of perinuclearly located lysosomes of tumor cells. Thx-peptide appeared with fluorescein-labeled peptide and peptide-DTPA-chelator complex in adenocarcinoma xenografts in mice. Conclusion: Thx shows promise for targeted imaging and drug delivery. © 2012 Federación de Sociedades Españolas de Oncología (FESEO).

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