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Abstract(Please copy/paste the abstract send to the congress) : |
Synthesis and radiolabeling of HYNIC-conjugated LIKKPF peptide with 18F-FDG for the detection of apoptosis
Davood beiki1, Sepideh Khoshbakht2, Soraya Shahhosseini3, Farzad Kobarfard3, Omid Sabzevari2, Mohsen Amini4
1Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran
2Dpartment of Radiopharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3Dpartment of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4Dpartment of Medicinal Chemistry, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Aim: Apoptosis, or programmed cell death, plays important roles in the physiology and pathology of a variety of human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. LIKKPF is a hexapeptide with high phosphatidylserine (PS) binding affinity in order to visualize cell death. 18F-FDG has so far been the most utilized radiotracer in positron emission tomography (PET) imaging. We herein report the synthesis of 18F-FDG-LIKKPF as a tracer for detecting apoptosis.
Materials and Methods: The peptide was synthesized by standard Fmoc solid phase synthesis and the HYNIC-conjugated LIKKPF was considered for the radiolabeling procedure with 18F-FDG. In order to optimize labeling efficiency, a series of studies including changing the amount of HYNIC-peptide ligand, adjustment of the reaction pH and varying the reaction temperature were performed.
Results: The radiochemical purity >50% was achieved for the radiolabelling procedure with 18F-FDG, in the presence of glucose (100-250 μg/mL). Also, stability studies in aqueous solution and human serum showed radiolabeled complex with no significant release of F-18 or peptide degradation up to 6 h.
Conclusion: Our results showed the high potential of 18F-FDG as 18F-fluorinated prosthetic group, to be clinically accepted for the radiolabelling of peptides such as LIKKPF for the detection of apoptosis.
A new lactam bridge 99mTc-α -melanocyte–stimulating hormone analog for diagnosis of metastatic melanoma
Abstract
Introduction: Over 80 % of human metastatic melanomas were reported to overexpress MC1 receptors. Since melanoma cause more than 75% of deaths from skin cancer, there is a need to develop new radiopharmaceuticals which allow diagnosing this type of tumor in an early phase.This study presents the synthesis of a new lactam bridge 99mTc-α-MSH analogue.
Methods: A new [HYNIC-GABA-Nle]-CycMSHheptderivative was conveniently synthesized by solid phase peptide synthesis on sieber amide resin via Fmoc strategy. Then peptide radiolabelling was performed by 99mTc via HYNIC chelator and tricine as co-ligand. Also, stability in human serum, receptor bound internalization, protein binding, partition coefficient and tissue biodistribution in tumor bearing nude mice were thoroughly investigated.
Results: The new peptide derivative was obtained in an overall yield of 35% with the purity of >98%. Radiolabeling with 99mTc was performed at high specific activities(163MBq/nmol)withan acceptable labeling yield (>98%).Also, stability studies in aqueous solution and human serum showed radiolabeled complex with no significant release of 99mTcO4− or peptide degradation up to 6 h. Protein binding and calculated partition coefficient for the radiolabeled peptide were 37% and log P=−1.31 ± 0.12 %, respectively.Also, the radioligand showed specific internalization into B16/F10 cells (13.35 ± 0.9% at 4 hours).In biodistribution studies, a receptor-specific uptake was observed in MC1 receptor positive organ so that after 4 hours the tumor uptake was 4.51±0.11 % ID/g.Predominant renal excretion pathway with a highest accumulation of activity in tumor was observed for this radiopeptide.
Conclusion:This new designed labeled peptide conjugate showed high accumulation in tumor as a positive MC1 receptor targeted tissue followed by excretion via the kidney and can be a suitable candidate for diagnosis of metastatic melanomas.
Evaluation of 99mTc-TRODAT-1 SPECT in the diagnosis of Parkinson’s disease and its differentiation from the other types of parkinsonism syndroms – A pilot study
D. Beiki1, A. Esmaeili1, B. Fallahi1, S. Oveisgharan2, H. Noorollahi-Moghaddam3, M. Erfani4, A. Tafakhori5, M. Rohani6, A. Fard-Esfahani1, A. Emami-Ardekani1, M. Eftekhari1;
1Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, IRAN, ISLAMIC REPUBLIC OF, 2Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, IRAN, ISLAMIC REPUBLIC OF, 3Shariati Hospital, Tehran University of Medical Sciences, Tehran, IRAN, ISLAMIC REPUBLIC OF, 4Radiation Application Research School, Nuclear Science and Technology Research Institute, Atomic Energy Organization of Iran, Tehran, Iran, Tehran, IRAN, ISLAMIC REPUBLIC OF, 5Department of Neurology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, IRAN, ISLAMIC REPUBLIC OF, 6Department of Neurology, School of Medicine, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, IRAN, ISLAMIC REPUBLIC OF.
Aims: Parkinson disease (PD) is one of the most common movement disorders. Sometimes, essential tremor (ET) and the other parkinsonian syndromes may manifest the same motor symptoms. In these cases, definite clinical diagnosis may be difficult. We conducted a study to determine the diagnostic value of 99mTc-TRODAT-1 scan to differentiate PD from ET and other cases of parkinsonism syndromes.
Methods and Materials: This study was prospectively performed on 35 patients including 15 PD, 12 ET and 8 patients with other parkinsonian syndromes (PS). A new analogue of 99mTc-TRODAT-1 was used for basal ganglia (BG) imaging. A dual-head SPECT-CT was used to perform imaging for all patients following administration of at least 950 MBq 99mTc-TRODAT-1. The images were reconstructed and processed using neuroimaging software for the SPECT modality. Drawing ROIs on the BG, the uptake values were estimated and normalized to whole brain uptake.
Results: Among three groups of patients, ET cases show significantly higher values of normalized BG uptake (p<0.05) as compared to PD and PS groups; however, no significant difference was noted between PD and PS groups. In qualitative assessment, all ET cases showed normal and symmetrical uptake in BG. From 15 PD patients, 9 cases (60%) revealed greater loss of uptake in putamen vs. cudate. On the other hand, in PS patients, 6 out of 8 patients (75%) had uniform pattern of decreased uptake in bilateral putamen and cudate and only two patients (25%) showed greater loss of uptake in putamen bilaterally, one symmetrical and the other one asymmetrical.
Conclusion: The preliminary quantitative data reveals that 99mTc-TRODAT-1 scan is a very appropriate method to differentiate PD or PS vs. ET cases. However, the BG uptake values alone could not identify PD vs. PS cases. The pattern of uptake may add to diagnostic value of the test; however, the present results are equivocal and thus further investigations with more cases are needed to reach more suitable criteria for this reason. |