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Abstract(Please copy/paste the abstract send to the congress) : |
18F-FDG-Aoe-LIKKP-Pyr-A: A new peptide radiotracer for apoptosis imaging
D. Beiki1, S. Khoshbakht2, S. Shahhosseini3, F. Kobarfard3, O. Sabzevari2, M. Amini4;
1Research Center for Nuclear Medicine, Shariati Hospital,
Tehran University of Medical Sciences, TEHRAN, IRAN, ISLAMIC REPUBLIC OF,
2Dpartment of Radiopharmacy, School of Pharmacy, Tehran University of Medical Sciences,
TEHRAN, IRAN, ISLAMIC REPUBLIC OF, 3Dpartment of Medicinal Chemistry,
School of Pharmacy, Shahid Beheshti University of Medical Sciences, TEHRAN, IRAN,
ISLAMIC REPUBLIC OF, 4Dpartment of Medicinal Chemistry, School of Pharmacy,
Tehran University of Medical Sciences, TEHRAN, IRAN, ISLAMIC REPUBLIC OF.
Aim: Specific biochemical changes occur in cells undergoing apoptosis that provide potential
targets for molecular imaging agents and imaging of apoptosis can provide a good way to predict
effectiveness of cancer chemotherapy. Clinical information obtained from targeting of
phosphatidyl serine (PS) would help to diagnosis and therapy of apoptosis related pathologies. A
few LIKKPF peptides with acceptable affinity for PS have been already introduced for apoptosis
imaging. We herein report the synthesis of a new LIKKPF peptide radiotracer with more affinity
for PS for detecting apoptosis.
Materials and Methods: The peptides were synthesized on solid phase using standard Fmoc
strategy, conjugated with aminooxy (Aoe), and then was considered for the radiolabeling
procedure with 18F-FDG. Biological properties were determined in vitro using camptothecin
treated Jurkat cells and in vivo using liver apoptosis mouse model induced via intraperitoneal (IP)
injection of lipopolysaccharide (LPS). Also, Log P values determination, biodistribution studies
and PET/CT imaging were performed.
Results: The radiochemical purity was >95% (100°C, 30 min, pH 5-5.5). Log P value for 18FDGAoe-
LIKKP-Pyr-A prepared by Fmoc-(4-pyridyl)-D-Ala-OH was -0.92. Kd of peptide was
determined with value 0.52 μM. Biodistribution results showed 3 times liver uptake for apoptotic
mice compared to normal mice. PET/CT images were in a good agreement with biodistribution
results. The activity ratio of liver to kidney was 0.17 and 0.61 in normal and apoptosis mouse
model, respectively.
Conclusion: 18FDG-Aoe-LIKKP-Pyr-A showed good affinity to PS and might be a potential
radiotracer for the detection of apoptosis.
18F-FDG-Aoe-LIKKP-Pyr-A: A new peptide radiotracer for apoptosis imaging
D. Beiki1, S. Khoshbakht2, S. Shahhosseini3, F. Kobarfard3, O. Sabzevari2, M. Amini4;
1Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, TEHRAN, IRAN, ISLAMIC REPUBLIC OF, 2Dpartment of Radiopharmacy, School of Pharmacy, Tehran University of Medical Sciences, TEHRAN, IRAN, ISLAMIC REPUBLIC OF, 3Dpartment of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, TEHRAN, IRAN, ISLAMIC REPUBLIC OF, 4Dpartment of Medicinal Chemistry, School of Pharmacy, Tehran University of Medical Sciences, TEHRAN, IRAN, ISLAMIC REPUBLIC OF.
Aim: Specific biochemical changes occur in cells undergoing apoptosis that provide potential targets for molecular imaging agents and imaging of apoptosis can provide a good way to predict effectiveness of cancer chemotherapy. Clinical information obtained from targeting of phosphatidyl serine (PS) would help to diagnosis and therapy of apoptosis related pathologies. A few LIKKPF peptides with acceptable affinity for PS have been already introduced for apoptosis imaging. We herein report the synthesis of a new LIKKPF peptide radiotracer with more affinity for PS for detecting apoptosis.
Materials and Methods: The peptides were synthesized on solid phase using standard Fmoc strategy, conjugated with aminooxy (Aoe), and then was considered for the radiolabeling procedure with 18F-FDG. Biological properties were determined in vitro using camptothecin treated Jurkat cells and in vivo using liver apoptosis mouse model induced via intraperitoneal (IP) injection of lipopolysaccharide (LPS). Also, Log P values determination, biodistribution studies and PET/CT imaging were performed.
Results: The radiochemical purity was >95% (100°C, 30 min, pH 5-5.5). Log P value for 18FDG-Aoe-LIKKP-Pyr-A prepared by Fmoc-(4-pyridyl)-D-Ala-OH was -0.92. Kd of peptide was determined with value 0.52 µM. Biodistribution results showed 3 times liver uptake for apoptotic mice compared to normal mice. PET/CT images were in a good agreement with biodistribution results. The activity ratio of liver to kidney was 0.17 and 0.61 in normal and apoptosis mouse model, respectively.
Conclusion: 18FDG-Aoe-LIKKP-Pyr-A showed good affinity to PS and might be a potential radiotracer for the detection of apoptosis.
Preparation and biological evaluation of 99mTc-HYNIC-LIKKPF for the detection of apoptosis
D. Beiki1, S. Khoshbakht2, S. Shahhosseini3, F. Kobarfard3, O. Sabzevari2, M. Amini4;
1Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, TEHRAN, IRAN, ISLAMIC REPUBLIC OF, 2Dpartment of Radiopharmacy, School of Pharmacy, Tehran University of Medical Sciences, TEHRAN, IRAN, ISLAMIC REPUBLIC OF, 3Dpartment of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, TEHRAN, IRAN, ISLAMIC REPUBLIC OF, 4Dpartment of Medicinal Chemistry, School of Pharmacy, Tehran University of Medical Sciences, TEHRAN, IRAN, ISLAMIC REPUBLIC OF.
Aim: Radioligands that have affinity and bind to phosphatidyl serine (PS) are good candidates for noninvasive imaging of apoptosis. Because of limitations of Annexin V (as a most studied imaging agent for apoptosis), there is a need to develop radioligands with better biodistribution profile for this purpose.
Materials and Methods: HYNIC-LIKKPF was successfully synthesized via Fmoc strategy and the compound was considered for the radiolabeling procedure with Tc-99m. Then, stability and Log P values of radiopeptide were determined. Finally, binding studies, biodistribution studies and SPECT/CT imaging were performed.
Results: The radiochemical purity and Log P value were >95% and -0.92, respecteviely. 99mTc-HYNIC-LIKKPF was stable in human serum for at least 2 hr at 37ºC. Although the affinity of radiolabeled LIKKPF was less than original phage peptide, the level of binding to apoptotic cells was 2.5 times higher than control cells. Biodistribution studies showed higher liver uptake of radiopeptide in apoptotic non-treated mouse model compare to normal and pre-treated mouse. The in vivo imaging results were consistent with biodistribution studies.
Conclusion: 99mTc-HYNIC-LIKKPF has less affinity to PS compare to original phage peptide, but high enough for specific binding to apoptotic cells in vitro and in vivo. Less affinity of radiolabeled LIKKPF might be attributed to hydrophobicity of peptide. The future peptides should be more hydrophobic compare to LIKKPF. |