Synthesis and analysis of 2-[211At]-l-phenylalanine and 4-[211At]-l-phenylalanine and their uptake in human glioma cell cultures in-vitro

Meyer, Geerd J.; Walte, Almut; Sriyapureddy, Siva R.; Grote, Michaela; Krull, Doris; Korkmaz, Zekiye; Knapp, Wolfram H.

doi:10.1016/j.apradiso.2009.12.043

Cited by 26 publications

(27 citation statements)

References 26 publications

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“…While attempts were made more than two decades ago to label tyrosine with 211 At, recently Meyer et al . [38] reported the synthesis of two 211 At-labeled phenylalanine derivatives, which were shown to undergo specific uptake in glioma cells in vitro . Finally, we have synthesized 211 At-labeled urea-based prostate-specific membrane antigen (PSMA) inhibitors that could potentially be useful in the targeted α-particle therapy of androgen-independent, advanced metastatic prostate cancers [39].…”

Section: At-labeled Radiopharmaceuticalsmentioning

confidence: 99%

Applications of 211At and 223Ra in Targeted Alpha-Particle Radiotherapy

Vaidyanathan¹,

Zalutsky²

2011

CRP

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Targeted radiotherapy using agents tagged with α-emitting radionuclides is gaining traction with several clinical trials already undertaken or ongoing, and others in the advanced planning stage. The most commonly used α-emitting radionuclides are 213Bi, 211At, 223Ra and 225Ac. While each one of these has pros and cons, it can be argued that 211At probably is the most versatile based on its half life, decay scheme and chemistry. On the other hand, for targeting bone metastases, 223Ra is the ideal radionuclide because simple cationic radium can be used for this purpose. In this review, we will discuss the recent developments taken place in the application of 211At-labeled radiopharmaceuticals and give an overview of the current status of 223Ra for targeted α-particle radiotherapy.

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Section: At-labeled Radiopharmaceuticalsmentioning

confidence: 99%

Applications of 211At and 223Ra in Targeted Alpha-Particle Radiotherapy

Vaidyanathan¹,

Zalutsky²

2011

CRP

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“…Due to the high polarizability, astatinated compounds often elute in between the brominated and iodinated homologues or even between the brominated and chlorinated homologues. 22 Further unexpected behaviour of astatine has been reported in nucleophilic substitution reactions with aryliodonium salts, where astatine gave much faster and slightly higher reaction yields than iodine, 23 a behaviour similar to the results in dediazotation reactions. 24 The ambivalent character of astatine led the Russian group to search for cationic species.…”

Section: Investigations Of Chemical Propertiesmentioning

confidence: 68%

“…When the series of F‐, Cl‐, Br‐, I‐, and At‐aromatic compounds are analysed under reversed phase or normal phase chromatographic conditions, the elution sequence is often not in the expected order. Due to the high polarizability, astatinated compounds often elute in between the brominated and iodinated homologues or even between the brominated and chlorinated homologues …”

Section: Investigations Of Chemical Propertiesmentioning

confidence: 99%

Astatine

Meyer

2018

Labelled Comp Radiopharmac

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This educational review describes and summarizes the historic discovery of element 85, the experiments leading to its physical and chemical characterization and comparison with its lighter homologue iodine. The half-lives of its longest living isotopes At and At with 8.3 and 7.22 hours respectively together with their alpha decay characteristics made these isotopes interesting for radiation biological research. However, the lack of stable isotopes of astatine presents a strong challenge for all characterizations. Nevertheless, the decay characteristics especially of At stimulated several research groups to develop labelling strategies for the preparation of astatinated radiopharmaceuticals for targeted alpha radiation therapy. Because of the distinct differences in the chemical behaviour of astatine, when compared with iodine, these approaches are quite challenging. Accordingly, quite different labelling strategies have been tested, namely nucleophilic and electrophilic substitution reactions as well as complex forming strategies. Classic and new developments for the preparation of these compounds are reviewed.

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“…We, on the other hand, used 15 seconds for radioiodination and 10 min at 65 °C for the deprotection of both Boc and tert -butyl ester groups. It should be pointed out that, in the synthesis of astatinated analogue (Meyer et al, 2010), the ester function in the tin precursor was converted to an acid before subjecting it to radiohalogenation thereby avoiding the hydrolysis step after radiolabeling. However, they have not elaborated on the hydrolysis process and thus it is not clear whether epimerization of the chiral carbon was a possibility.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, in general this reaction is the most practical route for the introduction of the ∀-particle-emitting heavy halogen 211 At into molecules of interest (Vaidyanathan and Zalutsky, 2008). Although astatinated phenylalanine has been obtained in considerably higher radiochemical yields by the copper-catalyzed astato-deiodination than by astato-destannylation (Meyer et al, 2010), separation of the radiohalogenated product from the chemically similar substrate, unlike from the tin precursor, could be challenging. Samnick's group developed an improved n.c.a.…”

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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Synthesis and analysis of 2-[211At]-l-phenylalanine and 4-[211At]-l-phenylalanine and their uptake in human glioma cell cultures in-vitro

Cited by 26 publications

References 26 publications

Applications of 211At and 223Ra in Targeted Alpha-Particle Radiotherapy

Applications of 211At and 223Ra in Targeted Alpha-Particle Radiotherapy

Astatine

An alternative and expedient synthesis of radioiodinated 4-iodophenylalanine

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