Synthesis of Stable Hydrazones of a Hydrazinonicotinyl-Modified Peptide for the Preparation of <sup>99m</sup>Tc-Labeled Radiopharmaceuticals

Harris, Thomas D.; Sworin, Michael; Williams, Neal E.; Rajopadhye, Milind; Damphousse, Paul R.; Głowacka, Danuta; Poirier, Michael J.; Yu, Karmine

doi:10.1021/bc9900237

Cited by 61 publications

(69 citation statements)

References 6 publications

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“…4). These results are consistent with those of other studies on linear peptide-based radiotracers (24,25). The metabolic instability of 99m Tc-HHK possibly contributes partially to its rapid clearance from tumor and normal organs.…”

Section: Discussionsupporting

confidence: 92%

Integrin α_vβ₆–Targeted SPECT Imaging for Pancreatic Cancer Detection

Liu

Líu

et al. 2014

J Nucl Med

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Integrin α v β 6 , a member of the integrin family, is specifically expressed in many malignancies but not in normal organs. Overexpression of integrin α v β 6 is usually correlated with malignant potential and poor prognosis. In this study, we describe the synthesis and evaluation of a 99m Tc-labeled integrin α v β 6 -targeting peptide as a SPECT radiotracer for the in vivo imaging of integrin α v β 6 expression. Methods: An integrin α v β 6 -targeting peptide (denoted as the HK peptide) was conjugated with 6-hydrazinonicotinyl (HYNIC) and radiolabeled with 99m Tc using tricine and TPPTS (trisodium triphenylphosphine-3,3′,3″-trisulfonate) as coligands. The in vitro and in vivo characteristics of 99m Tc-HYNIC(tricine)(TPPTS)-HK ( 99m Tc-HHK) were investigated in BxPC-3 (integrin α v β 6 -positive) and HEK293 (integrin α v β 6 -negative) models. The ability of 99m Tc-HHK to detect liver metastasis of pancreatic cancer was evaluated using small-animal SPECT/CT. Results: 99m Tc-HHK showed high integrin α v β 6 -binding specificity both in vitro and in vivo. 99m Tc-HHK was cleared rapidly from the blood and normal organs except for the kidneys. The highest uptake (0.88 ± 0.12 percentage injected dose per gram) of 99m Tc-HHK in BxPC-3 tumors was observed at 0.5 h after injection. High-contrast images of integrin α v β 6 -positive tumors were obtained using 99m Tc-HHK. The minimum nonspecific activity accumulation in normal liver tissues rendered high-quality SPECT/CT images of metastatic lesions. Conclusion: 99m Tc-HHK is a promising SPECT radiotracer for the noninvasive imaging of integrin α v β 6 expression in vivo. SPECT/ CT with 99m Tc-HHK could provide an effective approach for the noninvasive detection of primary and metastatic lesions of integrin α v β 6 -positive tumors.

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Section: Discussionsupporting

confidence: 92%

Integrin α_vβ₆–Targeted SPECT Imaging for Pancreatic Cancer Detection

Liu

Líu

et al. 2014

J Nucl Med

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“…Monomer: VNI Succinimidyl 6-[2-(4-dimethylamino)benzaldehydehydrazono] nicotinate was prepared from 6-hydrazinonicotinic acid according to the procedure of Harris et al (24). p-vinylbenzylamine (2.55 mmol) was added to a solution of succinimidyl 6-[2-(4-dimethylamino)benzaldehydehydrazono]nicotinate (2.65 mmol) in 20 mL of dry dimethyl formamide.…”

Section: Synthesis Of Hydrazinonicotinamide-carryingmentioning

confidence: 99%

Copolymer-Based Hepatocyte Asialoglycoprotein Receptor Targeting Agent for SPECT

Yang

Mou²,

Shao³

et al. 2011

J Nucl Med

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Poly(vinylbenzyl-O-b-D-galactopyranosyl-D-gluconamide) (PVLA) can be specifically internalized by hepatocytes via the asialoglycoprotein receptor. In this study, we synthesized and characterized galactose-carrying copolymers with hydrazinonicotinamide chains as bifunctional groups to radiolabel PVLA with 99m Tc for SPECT targeting specific hepatocytes. Methods:The copolymer was labeled with 99m Tc using tricine as a coligand. Then 99m Tc[P(VLA-co-VNI)](tricine) 2 was evaluated by in vivo metabolic stability and biodistribution in normal mice. SPECT was performed in normal New Zealand White rabbits and rabbits with liver cancer. Results: 99m Tc[P(VLA-co-VNI)](tricine) 2 was prepared in high labeling yield (.95%) and radiochemical purity (.99%), with good stability. The results of biodistribution in mice demonstrated that the liver uptake was 125.33 6 10.99 percentage injected dose per gram at 10 min after injection and could be blocked significantly by preinjecting free neogalactosylalbumin or P(VLA-co-VNI). SPECT images with high quality were obtained at 15, 30, 60, and 120 min after injection of the radiotracer. Significant radioactivity defect was observed in the liver cancer model. Conclusion: The bifunctional coupling agent hydrazinonicotinamide was introduced to PVLA via copolymerization and labeled with 99m Tc. The promising biologic properties of 99m Tc[P(VLA-co-VNI)](tricine) 2 afford potential applications for the assessment of hepatocyte function in the future.

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“…The cyclic RGDfK dimer, E[c(RGDfK)] 2 (SU016), was prepared according to the procedure described in our previous communication (2). Sodium succinimidyl 6-(2-(2-sulfonatobenzaldehyde)hydrazono)nicotinate (HYNIC-NHS) was prepared according to literature procedure (32). Na 99m TcO 4 was obtained from a DuPont Pharma 99 Mo/ 99m Tc generator, N. Billerica, MA.…”

Section: Experimental Section Materialsmentioning

confidence: 99%

Impact of PKM Linkers on Biodistribution Characteristics of the ^99mTc-Labeled Cyclic RGDfK Dimer

Liu

Hsieh

et al. 2006

Bioconjugate Chem.

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This report describes synthesis of three new cyclic RGDfK peptide conjugates, HYNIC-PKM-SU016 (PKM = E, K and PEG4), and in vivo evaluation of the impact of PKM linkers on biodistribution characteristics of their ternary ligand complexes [ 99m Tc(HYNIC-PKM-SU016)(tricine)(TPPTS)] in athymic nude mice bearing the MDA-MB-435 human breast cancer xenografts. Results from biodistribution studies show that PKM linkers have minimal impact on the integrin α v β 3 binding capability of radiotracers. Even though they have different charges under physiological conditions, all three linkers (E, K and PEG4) are able to reduce the uptake of 99m Tc-labeled E[c(RGDfK)] 2 in blood, kidneys, liver and lungs, and increase target-to-background (T/B) ratios at >30 min postinjection. E and K may have advantages over PEG4 due to a combination of relatively low liver uptake, high tumor/liver and tumor/lung ratios of ternary ligand complexes [ 99m Tc(HYNIC-PKM-SU016)(tricine)(TPPTS)] (PKM = E and K).

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Synthesis of Stable Hydrazones of a Hydrazinonicotinyl-Modified Peptide for the Preparation of ^99mTc-Labeled Radiopharmaceuticals

Cited by 61 publications

References 6 publications

Integrin α_vβ₆–Targeted SPECT Imaging for Pancreatic Cancer Detection

Integrin α_vβ₆–Targeted SPECT Imaging for Pancreatic Cancer Detection

Copolymer-Based Hepatocyte Asialoglycoprotein Receptor Targeting Agent for SPECT

Impact of PKM Linkers on Biodistribution Characteristics of the ^99mTc-Labeled Cyclic RGDfK Dimer

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Synthesis of Stable Hydrazones of a Hydrazinonicotinyl-Modified Peptide for the Preparation of 99mTc-Labeled Radiopharmaceuticals

Cited by 61 publications

References 6 publications

Integrin αvβ6–Targeted SPECT Imaging for Pancreatic Cancer Detection

Integrin αvβ6–Targeted SPECT Imaging for Pancreatic Cancer Detection

Copolymer-Based Hepatocyte Asialoglycoprotein Receptor Targeting Agent for SPECT

Impact of PKM Linkers on Biodistribution Characteristics of the 99mTc-Labeled Cyclic RGDfK Dimer

Contact Info

Product

Resources

About

Synthesis of Stable Hydrazones of a Hydrazinonicotinyl-Modified Peptide for the Preparation of ^99mTc-Labeled Radiopharmaceuticals

Integrin α_vβ₆–Targeted SPECT Imaging for Pancreatic Cancer Detection

Integrin α_vβ₆–Targeted SPECT Imaging for Pancreatic Cancer Detection

Impact of PKM Linkers on Biodistribution Characteristics of the ^99mTc-Labeled Cyclic RGDfK Dimer