Preparation and investigation of tumor affinity, uptake kinetic and transport mechanism of iodine-123-labelled amino acid derivatives in human pancreatic carcinoma and glioblastoma cells

Samnick, Samuel; Schaefer, A.; Siebert, Stefan; Richter, Sven; Vollmar, Brigitte; Kirsch, Carl-Martin

doi:10.1016/s0969-8051(00)00176-1

Cited by 35 publications

(17 citation statements)

References 28 publications

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“…Fractionated irradiation is typically used during radiation treatment to improve the therapeutic ratio between target and normal tissue. Given the nature of the carbon-ion radiotherapy, the normal healthy cells surrounding the target area generally will receive a low dose of low-LET radiation and can escape from radiation-damage, while the LET of the therapeutic carbon-ion beams in target area remains effective [ 44 ], thus the advantage gained by fractionation of a carbon-ion beam irradiation is significantly enhanced [ 36 ]. Considering this and because this study focused on the tumor responses post-irradiation of carbon-ion beam, single irradiations were used for both in vitro and in vivo studies.…”

Section: Discussionmentioning

confidence: 99%

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Amino acid transport system - A substrate predicts the therapeutic effects of particle radiotherapy

et al. 2017

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L-[methyl-11C]Methionine (11C-Met) is useful for estimating the therapeutic efficacy of particle radiotherapy at early stages of the treatment. Given the short half-life of 11C, the development of longer-lived 18F- and 123I-labeled probes that afford diagnostic information similar to 11C-Met, are being sought. Tumor uptake of 11C-Met is involved in many cellular functions such as amino acid transport System-L, protein synthesis, and transmethylation. Among these processes, since the energy-dependent intracellular functions involved with 11C-Met are more reflective of the radiotherapeutic effects, we evaluated the activity of the amino acid transport System-A as an another energy-dependent cellular function in order to estimate radiotherapeutic effects. In this study, using a carbon-ion beam as the radiation source, the activity of System-A was evaluated by a specific System-A substrate, alpha-[1-14C]-methyl-aminoisobutyric acid (14C-MeAIB). Cellular growth and the accumulation of 14C-MeAIB or 14C-Met were evaluated over time in vitro in cultured human salivary gland (HSG) tumor cells (3-Gy) or in vivo in murine xenografts of HSG tumors (6- or 25-Gy) before and after irradiation with the carbon-ion beam. Post 3-Gy irradiation, in vitro accumulation of 14C-Met and 14C-MeAIB decreased over a 5-day period. In xenografts of HSG tumors in mice, tumor re-growth was observed in vivo on day-10 after a 6-Gy irradiation dose, but no re-growth was detected after the 25-Gy irradiation dose. Consistent with the growth results, the in vivo tumor accumulation of 14C-MeAIB did not decrease after the 6-Gy irradiation dose, whereas a significant decrease was observed after the 25-Gy irradiation dose. These results indicate that the activity of energy dependent System-A transporter may reflect the therapeutic efficacy of carbon-ion radiotherapy and suggests that longer half-life radionuclide-labeled probes for System-A may also provide widely available probes to evaluate the effects of particle radiotherapy on tumors at early stage of the treatment.

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Section: Discussionmentioning

confidence: 99%

“…Cell uptake experiments were performed according to the procedure described by Samnick et al [ 36 ] with slight modifications. The cell suspension was transferred to a 15-mL tube and then centrifuged for 5 min at 1,000 x g .…”

Section: Methodsmentioning

confidence: 99%

Amino acid transport system - A substrate predicts the therapeutic effects of particle radiotherapy

et al. 2017

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“…Selective inhibitors of the amino acid transporter L, 2‐aminobicyclo[2,2,1]heptane‐2‐carboxylate (BCH; Sigma‐Aldrich) and of the amino acid transporter A, 2‐(methylamino)‐isobutyrate (MeAIB; Sigma‐Aldrich), were used as selective amino acid transporter inhibitors . To inhibit the alanine‐serine‐cysteine (ASC) transporter, L‐alanine, L‐serine, and L‐cysteine (all from Sigma‐Aldrich) were mixed together prior to use . 9L (4.0 × 10 5 cells/well) and C6 (4.5 × 10 5 cells/well) cultures were seeded in six‐well plates; the experiments were performed after 18–20 h once the cells had reached 60–70% confluency.…”

Section: Methodsmentioning

confidence: 99%

Biological evaluation of new [¹⁸F]F‐labeled synthetic amino acid derivatives as oncologic radiotracers

Kim

Lee

Yook

et al. 2016

Labelled Comp Radiopharmac

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The present study evaluated the tumoral uptake of the novel synthetic amino acid positron emission tomography (PET) tracers (S)-2-amino-3-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)propanoic acid (AMC-101), (S)-2-amino-4-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)butanoic acid (AMC-102), and (S)-2-amino-5-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)pentanoic acid (AMC-103), all of which are (S)-2-amino-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)alkyl acids. In vitro cellular uptake was investigated using the rat glioma cell lines 9L and C6. In vitro competitive inhibition tests were performed to identify the involvement of specific amino acid transporters. In vivo dynamic PET images of 9L xenograft tumor-bearing model mice were acquired over 2 h after AMC administration. [(18) F]FDOPA PET studies were performed with and without S-carbidopa pretreatment for comparison. All three AMCs exhibited good in vitro cell uptake through the L and alanine-serine-cysteine transporters and enabled clear tumor visualization on PET, leaving the brain devoid of the tracer. Thirty minutes after injection, the mean tumor standardized uptake values were 1.59 ± 0.05, 1.89 ± 0.27, and 1.74 ± 0.13 for AMC-101, AMC-102, and AMC-103, respectively. Although the tumor uptake values of AMCs were lower than that of [(18) F]FDOPA with S-carbidopa pretreatment, AMCs enabled higher contrast images with lower background activity compared with [(18) F]FDOPA with S-carbidopa pretreatment. Our results indicate the potential uses of these new synthetic amino acids as oncologic radiotracers.

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“…No-carrier-added (n.c.a.) synthesis of 4-[*I]iodophenylalanine by copper-catalyzed iodo-debromination has been reported by several groups including that of Samnick (Farah et al, 1997; Samnick et al, 2001). Halodestannylation is the most facile route for radioiodination—the reaction can be conducted under very mild conditions, results in higher radiochemical yields, and the product can be isolated devoid of any carrier.…”

Section: Introductionmentioning

confidence: 99%

An alternative and expedient synthesis of radioiodinated 4-iodophenylalanine

Vaidyanathan

McDougald

Grasfeder

et al. 2011

Applied Radiation and Isotopes

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Radiolabeled amino acids have been used extensively in oncology both as diagnostic and therapeutic agents. In our pursuit to develop radiopharmaceuticals to target breast cancer, we were interested in determining the uptake of radioiodinated 4-iodophenylalanine, among other labeled amino acids, in breast cancer cells. In this work, we have developed an alternative method for the synthesis of this agent. The novel tin precursor, (S)-tert-butyl 2-(tert-butoxycarbonylamino)-3-(4-(tributylstannyl)phenyl)propanoate (3) was synthesized from the known, corresponding iodo derivative. Initially, the labeled 4-iodophenylalanine was synthesized from the above tin precursor in two steps with radiochemical yields of 91.6 ± 2.7% and 83.7 ± 1.7% (n = 5), for the radioiodination (first) and deprotection (second) step, respectively. Subsequently, it was synthesized in a single step with an average radiochemical yield of 94.8 ± 3.4% (n = 5). After incubation with MCF-7 breast cancer cells for 60 min, an uptake up to 49.0 ± 0.7% of the input dose was seen; in comparison, the uptake of [14C]phenylalanine under the same conditions was 55.9 ± 0.5%. Furthermore, the uptake of both tracers was inhibited to a similar degree in a concentration-dependent manner by both unlabeled phenylalanine and 4-iodophenylalanine. With [14C]phenylalaine as the tracer, IC50 values of 1.45 mM and 2.50 mM were obtained for Phe and I-Phe, respectively and these values for [125I]I-Phe inhibition were 1.3 and 1.0 mM. In conclusion, an improved and convenient method for the synthesis of no-carrier-added 4-[*I]phenylalanine was developed and the radiotracer prepared by this route demonstrated an amino-acid transporter-mediated uptake in MCF-7 breast cancer cells in vitro that was comparable to that of [14C]phenylalanine.

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Preparation and investigation of tumor affinity, uptake kinetic and transport mechanism of iodine-123-labelled amino acid derivatives in human pancreatic carcinoma and glioblastoma cells

Cited by 35 publications

References 28 publications

Amino acid transport system - A substrate predicts the therapeutic effects of particle radiotherapy

Amino acid transport system - A substrate predicts the therapeutic effects of particle radiotherapy

Biological evaluation of new [¹⁸F]F‐labeled synthetic amino acid derivatives as oncologic radiotracers

An alternative and expedient synthesis of radioiodinated 4-iodophenylalanine

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Preparation and investigation of tumor affinity, uptake kinetic and transport mechanism of iodine-123-labelled amino acid derivatives in human pancreatic carcinoma and glioblastoma cells

Cited by 35 publications

References 28 publications

Amino acid transport system - A substrate predicts the therapeutic effects of particle radiotherapy

Amino acid transport system - A substrate predicts the therapeutic effects of particle radiotherapy

Biological evaluation of new [18F]F‐labeled synthetic amino acid derivatives as oncologic radiotracers

An alternative and expedient synthesis of radioiodinated 4-iodophenylalanine

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Biological evaluation of new [¹⁸F]F‐labeled synthetic amino acid derivatives as oncologic radiotracers