Non-macrocyclic H4OCTAPA derivatives form highly stable complexes with Bi(iii), but require an ap... more Non-macrocyclic H4OCTAPA derivatives form highly stable complexes with Bi(iii), but require an appropriate rigid spacer to enhance the inertness of the complex, as demonstrated by radiolabeling studies with 205/206Bi-nuclides.
Since NGR-tripeptides (asparagine-glycine-arginine) selectively target neoangiogenesis-associated... more Since NGR-tripeptides (asparagine-glycine-arginine) selectively target neoangiogenesis-associated Aminopeptidase N (APN/CD13) on cancer cells, we aimed to evaluate the in vivo tumour targeting capability of radiolabelled, NGR-containing, ANP/CD13-selective [213Bi]Bi-DOTAGA-cKNGRE in CD13pos. HT1080 fibrosarcoma-bearing severe combined immunodeficient CB17 mice. 10 ± 1 days after cancer cell inoculation, positron emission tomography (PET) was performed applying [68Ga]Ga-DOTAGA-cKNGRE for tumour verification. On the 7th, 8th, 10th and 12th days the treated group of tumourous mice were intraperitoneally administered with 4.68 ± 0.10 MBq [213Bi]Bi-DOTAGA-cKNGRE, while the untreated tumour-bearing animals received 150 μL saline solution. In addition to body weight (BW) and tumour volume measurements, ex vivo biodistribution studies were conducted 30 and 90 min postinjection (pi.). The following quantitative standardised uptake values (SUV) confirmed the detectability of the HT1080 tumour...
Since NGR-tripeptides (asparagine-glycine-arginine) selectively target neoangiogenesis-associated... more Since NGR-tripeptides (asparagine-glycine-arginine) selectively target neoangiogenesis-associated Aminopeptidase N (APN/CD13) on cancer cells, we aimed to evaluate the in vivo tumour targeting capability of radiolabelled, NGR-containing, ANP/CD13-selective [213Bi]Bi-DOTAGA-cKNGRE in CD13pos. HT1080 fibrosarcoma-bearing severe combined immunodeficient CB17 mice. 10 ± 1 days after cancer cell inoculation, positron emission tomography (PET) was performed applying [68Ga]Ga-DOTAGA-cKNGRE for tumour verification. On the 7th, 8th, 10th and 12th days the treated group of tumourous mice were intraperitoneally administered with 4.68 ± 0.10 MBq [213Bi]Bi-DOTAGA-cKNGRE, while the untreated tumour-bearing animals received 150 μL saline solution. In addition to body weight (BW) and tumour volume measurements, ex vivo biodistribution studies were conducted 30 and 90 min postinjection (pi.). The following quantitative standardised uptake values (SUV) confirmed the detectability of the HT1080 tumour...
International Journal of Molecular Sciences, Sep 2, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
"PET based" molecular imaging has significant role in personalized medicine. New radiop... more "PET based" molecular imaging has significant role in personalized medicine. New radiopharmaceuticals are continuously introduced into the daily practice of detecting diseases and assessing the effectiveness of therapy. In recent years theragnostic applications have come to the forefront of radiopharmaceutical development. This article discusses, among others, radiopharmaceuticals labelled with 18F and 68Ga isotopes required for the diagnosis of neuroendocrine and prostate tumours, furthermore the inhibitors of the fibroblast activation protein. The increasing variety of metallic radioisotopes (44Sc, 64Cu, 52Mn, 86Y, 89Zr) will help meet the need for new biomarkers and will greatly facilitate the introduction of the new generation of PET radiopharmaceuticals.
We have discovered five bismuth(III)-containing polyoxopalladates (POPs) which were fully charact... more We have discovered five bismuth(III)-containing polyoxopalladates (POPs) which were fully characterized by solution and solid-state physicochemical techniques: the cube-shaped [BiPd 12 O 32 (AsPh) 8 ] 5− (BiPd 12 AsL), [BiPd 12 O 32 (AsC 6 H 4 N 3) 8 ] 5− (BiPd 12 AsL N), and [BiPd 12 O 32 (AsC 6 H 4 COO) 8 ] 13− (BiPd 12 AsL C) as well as the star-shaped [BiPd 15 O 40-(PO) 10 H 6 ] 11− (BiPd 15 P) and [BiPd 15 O 40 (PPh) 10 ] 7− (BiPd 15 PL), respectively. The organically modified capping groups phenylarsonate, p-azidophenylarsonate, and p-carboxyphenylarsonate were chosen as the azido (−N 3) and carboxyl (−COOH) groups open up opportunities to covalently conjugate (via click reaction, amide coupling, etc.) with targeting vectors. The synthesis of p-azidophenylarsonate is reported here for the first time. The effects of the Bi III template and the organoarsonate vs −posphonate capping groups on the resulting POP shape (cube vs star) are discussed. The 209 Bi NMR (I = 9/2) spectra of BiPd 12 AsL, BiPd 12 AsL N , and BiPd 12 AsL C revealed narrow peaks (ν 1/2 ∼ 200 Hz) at 5470 ppm with a longitudinal relaxation time in the millisecond range (at 8.46 T). The absence of a quadrupolar relaxation contribution could be attributed to the allocation of Bi III in the highly symmetrical cuboid POP host cage. Similar peaks were absent in the 209 Bi-NMR spectra of the star-shaped POPs BiPd 15 P and BiPd 15 PL due to the less symmetric coordination environment around the central Bi III ion. Further, 205/206 Bi-radiolabeled POPs have been synthesized by incorporating a 205/206 Bi III ion in the center of the POP structures. Carrier-free 205/206 Bi radioisotopes (as surrogates of α-emitting 213 Bi) were incorporated into the POP host-cage for the preparation of 205/206 BiPd 12 AsL, 205/206 BiPd 12 AsL N , 205/206 BiPd 12 AsL C , and 205/206 BiPd 15 PL, respectively. The radiometal incorporation was complete (>99% radiochemical yield) in 10 min according to radiothin-layer chromatography. The 205/206 BiPd 12 AsL polyanion was purified by solid-phase extraction. The incubation in rat serum showed the formation of a 205/206 BiPd 12 AsL−protein aggregate.
Hypoxia promotes angiogenesis, which is crucial for tumor growth, and induces malignant progressi... more Hypoxia promotes angiogenesis, which is crucial for tumor growth, and induces malignant progression and increases the therapeutic resistance. Positron emission tomography (PET) enables the detection of the hypoxic regions in tumors using 2-nitroimidazole-based radiopharmaceuticals. We describe here a physicochemical study of the Sc(DO3AM-NI) complex, which indicates: (a) relatively slow formation of the Sc(DO3AM-NI) chelate in acidic solution; (b) lower thermodynamic stability than the reference Sc(DOTA); (c) however, it is substantially more inert and consequently can be regarded as an excellent Sc-binder system. In addition, we report a comparison of 44Sc-labeled DO3AM-NI with its known 68Ga-labeled analog as a hypoxia PET probe. The in vivo and ex vivo biodistributions of 44Sc- and 68Ga-labeled DO3AM-NI in healthy and KB tumor-bearing SCID mice were examined 90 and 240 min after intravenous injection. No significant difference was found between the accumulation of 44Sc- and 68Ga-...
Non-macrocyclic H4OCTAPA derivatives form highly stable complexes with Bi(iii), but require an ap... more Non-macrocyclic H4OCTAPA derivatives form highly stable complexes with Bi(iii), but require an appropriate rigid spacer to enhance the inertness of the complex, as demonstrated by radiolabeling studies with 205/206Bi-nuclides.
Since NGR-tripeptides (asparagine-glycine-arginine) selectively target neoangiogenesis-associated... more Since NGR-tripeptides (asparagine-glycine-arginine) selectively target neoangiogenesis-associated Aminopeptidase N (APN/CD13) on cancer cells, we aimed to evaluate the in vivo tumour targeting capability of radiolabelled, NGR-containing, ANP/CD13-selective [213Bi]Bi-DOTAGA-cKNGRE in CD13pos. HT1080 fibrosarcoma-bearing severe combined immunodeficient CB17 mice. 10 ± 1 days after cancer cell inoculation, positron emission tomography (PET) was performed applying [68Ga]Ga-DOTAGA-cKNGRE for tumour verification. On the 7th, 8th, 10th and 12th days the treated group of tumourous mice were intraperitoneally administered with 4.68 ± 0.10 MBq [213Bi]Bi-DOTAGA-cKNGRE, while the untreated tumour-bearing animals received 150 μL saline solution. In addition to body weight (BW) and tumour volume measurements, ex vivo biodistribution studies were conducted 30 and 90 min postinjection (pi.). The following quantitative standardised uptake values (SUV) confirmed the detectability of the HT1080 tumour...
Since NGR-tripeptides (asparagine-glycine-arginine) selectively target neoangiogenesis-associated... more Since NGR-tripeptides (asparagine-glycine-arginine) selectively target neoangiogenesis-associated Aminopeptidase N (APN/CD13) on cancer cells, we aimed to evaluate the in vivo tumour targeting capability of radiolabelled, NGR-containing, ANP/CD13-selective [213Bi]Bi-DOTAGA-cKNGRE in CD13pos. HT1080 fibrosarcoma-bearing severe combined immunodeficient CB17 mice. 10 ± 1 days after cancer cell inoculation, positron emission tomography (PET) was performed applying [68Ga]Ga-DOTAGA-cKNGRE for tumour verification. On the 7th, 8th, 10th and 12th days the treated group of tumourous mice were intraperitoneally administered with 4.68 ± 0.10 MBq [213Bi]Bi-DOTAGA-cKNGRE, while the untreated tumour-bearing animals received 150 μL saline solution. In addition to body weight (BW) and tumour volume measurements, ex vivo biodistribution studies were conducted 30 and 90 min postinjection (pi.). The following quantitative standardised uptake values (SUV) confirmed the detectability of the HT1080 tumour...
International Journal of Molecular Sciences, Sep 2, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
"PET based" molecular imaging has significant role in personalized medicine. New radiop... more "PET based" molecular imaging has significant role in personalized medicine. New radiopharmaceuticals are continuously introduced into the daily practice of detecting diseases and assessing the effectiveness of therapy. In recent years theragnostic applications have come to the forefront of radiopharmaceutical development. This article discusses, among others, radiopharmaceuticals labelled with 18F and 68Ga isotopes required for the diagnosis of neuroendocrine and prostate tumours, furthermore the inhibitors of the fibroblast activation protein. The increasing variety of metallic radioisotopes (44Sc, 64Cu, 52Mn, 86Y, 89Zr) will help meet the need for new biomarkers and will greatly facilitate the introduction of the new generation of PET radiopharmaceuticals.
We have discovered five bismuth(III)-containing polyoxopalladates (POPs) which were fully charact... more We have discovered five bismuth(III)-containing polyoxopalladates (POPs) which were fully characterized by solution and solid-state physicochemical techniques: the cube-shaped [BiPd 12 O 32 (AsPh) 8 ] 5− (BiPd 12 AsL), [BiPd 12 O 32 (AsC 6 H 4 N 3) 8 ] 5− (BiPd 12 AsL N), and [BiPd 12 O 32 (AsC 6 H 4 COO) 8 ] 13− (BiPd 12 AsL C) as well as the star-shaped [BiPd 15 O 40-(PO) 10 H 6 ] 11− (BiPd 15 P) and [BiPd 15 O 40 (PPh) 10 ] 7− (BiPd 15 PL), respectively. The organically modified capping groups phenylarsonate, p-azidophenylarsonate, and p-carboxyphenylarsonate were chosen as the azido (−N 3) and carboxyl (−COOH) groups open up opportunities to covalently conjugate (via click reaction, amide coupling, etc.) with targeting vectors. The synthesis of p-azidophenylarsonate is reported here for the first time. The effects of the Bi III template and the organoarsonate vs −posphonate capping groups on the resulting POP shape (cube vs star) are discussed. The 209 Bi NMR (I = 9/2) spectra of BiPd 12 AsL, BiPd 12 AsL N , and BiPd 12 AsL C revealed narrow peaks (ν 1/2 ∼ 200 Hz) at 5470 ppm with a longitudinal relaxation time in the millisecond range (at 8.46 T). The absence of a quadrupolar relaxation contribution could be attributed to the allocation of Bi III in the highly symmetrical cuboid POP host cage. Similar peaks were absent in the 209 Bi-NMR spectra of the star-shaped POPs BiPd 15 P and BiPd 15 PL due to the less symmetric coordination environment around the central Bi III ion. Further, 205/206 Bi-radiolabeled POPs have been synthesized by incorporating a 205/206 Bi III ion in the center of the POP structures. Carrier-free 205/206 Bi radioisotopes (as surrogates of α-emitting 213 Bi) were incorporated into the POP host-cage for the preparation of 205/206 BiPd 12 AsL, 205/206 BiPd 12 AsL N , 205/206 BiPd 12 AsL C , and 205/206 BiPd 15 PL, respectively. The radiometal incorporation was complete (>99% radiochemical yield) in 10 min according to radiothin-layer chromatography. The 205/206 BiPd 12 AsL polyanion was purified by solid-phase extraction. The incubation in rat serum showed the formation of a 205/206 BiPd 12 AsL−protein aggregate.
Hypoxia promotes angiogenesis, which is crucial for tumor growth, and induces malignant progressi... more Hypoxia promotes angiogenesis, which is crucial for tumor growth, and induces malignant progression and increases the therapeutic resistance. Positron emission tomography (PET) enables the detection of the hypoxic regions in tumors using 2-nitroimidazole-based radiopharmaceuticals. We describe here a physicochemical study of the Sc(DO3AM-NI) complex, which indicates: (a) relatively slow formation of the Sc(DO3AM-NI) chelate in acidic solution; (b) lower thermodynamic stability than the reference Sc(DOTA); (c) however, it is substantially more inert and consequently can be regarded as an excellent Sc-binder system. In addition, we report a comparison of 44Sc-labeled DO3AM-NI with its known 68Ga-labeled analog as a hypoxia PET probe. The in vivo and ex vivo biodistributions of 44Sc- and 68Ga-labeled DO3AM-NI in healthy and KB tumor-bearing SCID mice were examined 90 and 240 min after intravenous injection. No significant difference was found between the accumulation of 44Sc- and 68Ga-...
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