Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cells
OBJECTIVES: Cancer has been investigated using various pre-targeting techniques or models focusing on radiobombesin analogues; however, both are not offered together. In this study, nano-bombesin labeling by a pre-targeting system was undertaken to develop an alternative approach for prostate tumor...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier España
2011-01-01
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| Series: | Clinics |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322011000200024 |
| _version_ | 1828196906544660480 |
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| author | Bluma Linkowski Faintuch Gustavo Eutimio Fernandez Núñez Rodrigo Teodoro Ana M. Moro Jair Mengatti |
| author_facet | Bluma Linkowski Faintuch Gustavo Eutimio Fernandez Núñez Rodrigo Teodoro Ana M. Moro Jair Mengatti |
| author_sort | Bluma Linkowski Faintuch |
| collection | DOAJ |
| description | OBJECTIVES: Cancer has been investigated using various pre-targeting techniques or models focusing on radiobombesin analogues; however, both are not offered together. In this study, nano-bombesin labeling by a pre-targeting system was undertaken to develop an alternative approach for prostate tumor treatment. METHODS: A two-step pre-targeting system utilizing a combination of streptavidin (SA), biotinylated morpholino (B-MORF), biotinylated BBN (B-BBN) with two different spacers (b-Ala and PEG), and a radiolabeled cMORF was evaluated in vitro and in vivo. RESULTS: Final conjugation conditions consisted of a 1:1:2 ratio of SA:B-MORF:B-BBN, followed by addition of 99mTc-cMORF to compensate for free MORF. In vitro binding experiments with prostate cancer cells (PC-3) revealed that total binding was time-dependent for the Ala spacer but not for the PEG spacer. The highest accumulation (5.06 ± 1.98 %) was achieved with 1 hour of incubation, decreasing as time progressed. Specific binding fell to 1.05 ± 0.35 %. The pre-targeting biodistribution in healthy Swiss mice was measured at different time points, with the best responses observed for 7-h and 15-h incubations. The effector, 99mTc-MAG3-cMORF, was administered 2 h later. Strong kidney excretion was always documented. The greatest tumor uptake was 2.58 ± 0.59 %ID/g at 7 h for B-bAla-BBN, with a region of interest (ROI) value of 3.9 % during imaging. The tumor/blood ratio was low due to the slow blood clearance; however, the tumor/muscle ratio was 5.95. CONCLUSIONS: The pre-targeting approach with a peptide was a viable concept. Further evaluation with modified sequences of MORF, including less cytosine, and additional test intervals could be worthwhile. |
| first_indexed | 2024-04-12T10:11:15Z |
| format | Article |
| id | doaj.art-84a9ee6965bb40cdb05fd26aaa9efeef |
| institution | Directory Open Access Journal |
| issn | 1807-5932 1980-5322 |
| language | English |
| last_indexed | 2024-04-12T10:11:15Z |
| publishDate | 2011-01-01 |
| publisher | Elsevier España |
| record_format | Article |
| series | Clinics |
| spelling | doaj.art-84a9ee6965bb40cdb05fd26aaa9efeef2022-12-22T03:37:19ZengElsevier EspañaClinics1807-59321980-53222011-01-0166232733610.1590/S1807-59322011000200024Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cellsBluma Linkowski FaintuchGustavo Eutimio Fernandez NúñezRodrigo TeodoroAna M. MoroJair MengattiOBJECTIVES: Cancer has been investigated using various pre-targeting techniques or models focusing on radiobombesin analogues; however, both are not offered together. In this study, nano-bombesin labeling by a pre-targeting system was undertaken to develop an alternative approach for prostate tumor treatment. METHODS: A two-step pre-targeting system utilizing a combination of streptavidin (SA), biotinylated morpholino (B-MORF), biotinylated BBN (B-BBN) with two different spacers (b-Ala and PEG), and a radiolabeled cMORF was evaluated in vitro and in vivo. RESULTS: Final conjugation conditions consisted of a 1:1:2 ratio of SA:B-MORF:B-BBN, followed by addition of 99mTc-cMORF to compensate for free MORF. In vitro binding experiments with prostate cancer cells (PC-3) revealed that total binding was time-dependent for the Ala spacer but not for the PEG spacer. The highest accumulation (5.06 ± 1.98 %) was achieved with 1 hour of incubation, decreasing as time progressed. Specific binding fell to 1.05 ± 0.35 %. The pre-targeting biodistribution in healthy Swiss mice was measured at different time points, with the best responses observed for 7-h and 15-h incubations. The effector, 99mTc-MAG3-cMORF, was administered 2 h later. Strong kidney excretion was always documented. The greatest tumor uptake was 2.58 ± 0.59 %ID/g at 7 h for B-bAla-BBN, with a region of interest (ROI) value of 3.9 % during imaging. The tumor/blood ratio was low due to the slow blood clearance; however, the tumor/muscle ratio was 5.95. CONCLUSIONS: The pre-targeting approach with a peptide was a viable concept. Further evaluation with modified sequences of MORF, including less cytosine, and additional test intervals could be worthwhile.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322011000200024RadiolabelingTechnetium-99mHuman tumor PC-3 cellsPeptideTumor uptake |
| spellingShingle | Bluma Linkowski Faintuch Gustavo Eutimio Fernandez Núñez Rodrigo Teodoro Ana M. Moro Jair Mengatti Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cells Clinics Radiolabeling Technetium-99m Human tumor PC-3 cells Peptide Tumor uptake |
| title | Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cells |
| title_full | Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cells |
| title_fullStr | Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cells |
| title_full_unstemmed | Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cells |
| title_short | Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cells |
| title_sort | radiolabeled nano peptides show specificity for an animal model of human pc3 prostate cancer cells |
| topic | Radiolabeling Technetium-99m Human tumor PC-3 cells Peptide Tumor uptake |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322011000200024 |
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