Publications by authors named "Rubagotti Sara"

13 Publications

  • Page 1 of 1

Preliminary Study of a 1,5-Benzodiazepine-Derivative Labelled with Indium-111 for CCK-2 Receptor Targeting.

Molecules 2021 Feb 9;26(4). Epub 2021 Feb 9.

Radiopharmaceutical Chemistry Section, Nuclear Medicine Unit, AUSL-IRCCS di Reggio Emilia, Viale Risorgimento 80, 42122 Reggio Emilia, Italy.

The cholecystokinin-2 receptor (CCK-2R) is overexpressed in several human cancers but displays limited expression in normal tissues. For this reason, it is a suitable target for developing specific radiotracers. In this study, a nastorazepide-based ligand functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator (IP-001) was synthesized and labelled with indium-111. The radiolabeling process yielded >95% with a molar activity of 10 MBq/nmol and a radiochemical purity of >98%. Stability studies have shown a remarkable resistance to degradation (>93%) within 120 h of incubation in human blood. The in vitro uptake of [In]In-IP-001 was assessed for up to 24 h on a high CCK-2R-expressing tumor cell line (A549) showing maximal accumulation after 4 h of incubation. Biodistribution and single photon emission tomography (SPECT)/CT imaging were evaluated on BALB/c nude mice bearing A549 xenograft tumors. Implanted tumors could be clearly visualized after only 4 h post injection (2.36 ± 0.26% ID/cc), although a high amount of radiotracer was also found in the liver, kidneys, and spleen (8.25 ± 2.21%, 6.99 ± 0.97%, and 3.88 ± 0.36% ID/cc, respectively). Clearance was slow by both hepatobiliary and renal excretion. Tumor retention persisted for up to 24 h, with the tumor to organs ratio increasing over-time and ending with a tumor uptake (1.52 ± 0.71% ID/cc) comparable to liver and kidneys.
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http://dx.doi.org/10.3390/molecules26040918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916174PMC
February 2021

Gallium-68 and scandium-44 labelled radiotracers based on curcumin structure linked to bifunctional chelators: Synthesis and characterization of potential PET radiotracers.

J Inorg Biochem 2020 03 5;204:110954. Epub 2019 Dec 5.

Radiopharmaceutical Chemistry Section, Nuclear Medicine Unit, Azienda USL-IRCCS Reggio Emilia, via Amendola 2, 42122 Reggio Emilia, Italy.

Curcumin metal complexes showed widespread applications in medicine and can be exploited as a lead structure for developing new tracers for nuclear medicine application. Herein, the synthesis, chemical characterization and radiolabelling with gallium-68 and scandium-44 of two new targeting vectors based on curcumin scaffolds and linked to the chelators 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) and 1,4-bis(carboxymethyl)-6-[bis(carboxymethyl)]amino-6-methylperhydro-1,4-diazepine (AAZTA) are reported. Synthesis of the precursors could be achieved with a 13% and 11% yield and radiolabelling generally afforded rapid incorporation under mild conditions (>95%). Stability in physiological media (~75% after 2 h in human blood for [Ga]Ga-/[Sc]Sc-AAZTA-PC21 and ~60% for [Ga]Ga-NODAGA-C21, respectively) are generally enhanced if compared to the previously radiolabelled analogues. MS fragmentation experiments showed high stability of the AAZTA-PC21 structure mainly due to the pyrazole derivatization of the curcumin keto-enol moiety and a more feasible radiolabelling was noticed both with gallium-68 and scandium-44 mainly due to the AAZTA-chelator properties. [Ga]Ga-NODAGA-C21 showed the most favorable lipophilicity value (logD = 1.3). Due to these findings, both compounds appear to be promising candidates for the imaging of colorectal cancer, but further studies such as in vitro uptake and in vivo biodistribution experiments are needed.
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http://dx.doi.org/10.1016/j.jinorgbio.2019.110954DOI Listing
March 2020

Cu and fluorescein labeled anti-miRNA peptide nucleic acids for the detection of miRNA expression in living cells.

Sci Rep 2019 03 4;9(1):3376. Epub 2019 Mar 4.

Nuclear Medicine Unit, Oncology and Advanced Technologies Department, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42123, Reggio Emilia, Italy.

MiRNAs are single stranded RNAs of 18-22 nucleotides. They are promising diagnostic and prognostic markers for several pathologies including tumors, neurodegenerative, cardiovascular and autoimmune diseases. In the present work the development and characterization of anti-miRNA radiolabeled probes based on peptide nucleic acids (PNAs) for potential non-invasive molecular imaging in vivo of giant cell arteritis are described. MiR-146a and miR-146b-5p were selected as targets because they have been found up-regulated in this disease. Anti-miR and scramble PNAs were synthesized and linked to carboxyfluorescein or DOTA. DOTA-anti-miR PNAs were then labelled with copper-64 (Cu) to function as non-invasive molecular imaging tools. The affinity of the probes for the targets was assessed in vitro by circular dichroism and melting temperature. Differential uptake of fluorescein and Cu labeled anti-miRNA probes was tested on BCPAP and A549 cell lines, expressing different levels of miR-146a and -146b-5p. The experiments showed that the anti-miR-146a PNAs were more effective than the anti-miR-146b-5p PNAs. Anti-miR-146a PNAs could bind both miR-146a and miR-146b-5p. The uptake of fluorescein and Cu labeled anti-miR-146a PNAs was higher than that of the negative control scramble PNAs in miRNA expressing cells in vitro. Cu-anti-miR-146a PNAs might be further investigated for non-invasive PET imaging of miR-146 overexpressing diseases.
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http://dx.doi.org/10.1038/s41598-018-35800-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399270PMC
March 2019

Development of a Potential Gallium-68-Labelled Radiotracer Based on DOTA-Curcumin for Colon-Rectal Carcinoma: From Synthesis to In Vivo Studies.

Molecules 2019 Feb 12;24(3). Epub 2019 Feb 12.

Radiopharmaceutical Chemistry Unit, Oncologic and High Technologies Department, Azienda USL-IRCCS, via Amendola 2, 42122 Reggio Emilia, Italy.

Colorectal cancer is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women worldwide. We have recently reported that curcuminoid complexes labelled with gallium-68 have demonstrated preferential uptake in HT29 colorectal cancer and K562 lymphoma cell lines compared to normal human lymphocytes. In the present study, we report a new gallium-68-labelled curcumin derivative (Ga-DOTA-C21) and its initial validation as marker for early detection of colorectal cancer. The precursor and non-radioactive complexes were synthesized and deeply characterized by analytical methods then the curcuminoid was radiolabelled with gallium-68. The in vitro stability, cell uptake, internalization and efflux properties of the probe were studied in HT29 cells, and the in vivo targeting ability and biodistribution were investigated in mice bearing HT29 subcutaneous tumour model. Ga-DOTA-C21 exhibits decent stability (57 ± 3% after 120 min of incubation) in physiological media and a curcumin-mediated cellular accumulation in colorectal cancer cell line (121 ± 4 KBq of radiotracer per mg of protein within 60 min of incubation). In HT29 tumour-bearing mice, the tumour uptake of Ga-DOTA-C21 is 3.57 ± 0.3% of the injected dose per gram of tissue after 90 min post injection with a tumour to muscle ratio of 2.2 ± 0.2. High amount of activity (12.73 ± 1.9% ID/g) is recorded in blood and significant uptake of the radiotracer occurs in the intestine (13.56 ± 3.3% ID/g), lungs (8.42 ± 0.8% ID/g), liver (5.81 ± 0.5% ID/g) and heart (4.70 ± 0.4% ID/g). Further studies are needed to understand the mechanism of accumulation and clearance; however, Ga-DOTA-C21 provides a productive base-structure to develop further radiotracers for imaging of colorectal cancer.
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http://dx.doi.org/10.3390/molecules24030644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384893PMC
February 2019

Labelling of Y- and Lu-DOTA-Bioconjugates for Targeted Radionuclide Therapy: A Comparison among Manual, Semiautomated, and Fully Automated Synthesis.

Contrast Media Mol Imaging 2017 25;2017:8160134. Epub 2017 May 25.

Nuclear Medicine Unit, Oncology and Advanced Technologies Department, Arcispedale Santa Maria Nuova-IRCCS, 42123 Reggio Emilia, Italy.

In spite of the hazard due to the radiation exposure, preparation of Y- and Lu-labelled radiopharmaceuticals is still mainly performed using manual procedures. In the present study the performance of a commercial automatic synthesizer based on disposable cassettes for the labelling of Lu- and Y-DOTA-conjugated biomolecules (namely, DOTATOC and PSMA-617) was evaluated and compared to a manual and a semiautomated approach. The dose exposure of the operators was evaluated as well. More than 300 clinical preparations of both Y- and Lu-labelled radiopharmaceuticals have been performed using the three different methods. The mean radiochemical yields for Y-DOTATOC were 96.2 ± 4.9%, 90.3 ± 5.6%, and 82.0 ± 8.4%, while for Lu-DOTATOC they were 98.3%  ± 0.6, 90.8%  ± 8.3, and 83.1 ± 5.7% when manual, semiautomated, and automated approaches were used, respectively. The mean doses on the whole hands for yttrium-90 preparations were 0.15 ± 0.4 mSv/GBq, 0.04 ± 0.1 mSv/GBq, and 0.11 ± 0.3 mSv/GBq for manual, semiautomated, and automated synthesis, respectively, and for lutetium-177 preparations, they were 0.02 ± 0.008 mSv/GBq, 0.01 ± 0.03 mSv/GBq, and 0.01 ± 0.02 mSv/GBq, respectively. In conclusion, the automated approach guaranteed reliable and reproducible preparations of pharmaceutical grade therapeutic radiopharmaceuticals in a decent RCY. The radiation exposure of the operators remained comparable to the manual approach mainly due to the fact that a dedicated shielding was still not available for the system.
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http://dx.doi.org/10.1155/2017/8160134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612754PMC
August 2018

Uptake of Ga-curcumin derivatives in different cancer cell lines: Toward the development of new potential Ga-labelled curcuminoids-based radiotracers for tumour imaging.

J Inorg Biochem 2017 08 10;173:113-119. Epub 2017 May 10.

Nuclear Medicine Unit, Oncology and Advanced Technologies Department, Arcispedale Santa Maria Nuova-IRCCS, 42123 Reggio Emilia, Italy.

Thanks to the ability to suppress the proliferation and to kill tumour cells, several studies have shown the anti-cancer effects of curcumin (CUR) and its derivatives, i.e. diacetylcurcumin (DAC) and bis-dehydroxycurcumin (bDHC). This study is focused onto the development of curcuminoid complexes with gallium-68 employed as potential new radio-labelled probes to detect neoplastic tissues through imaging techniques such as positron emission tomography. To this purpose, the uptake of three Ga-curcuminoid complexes, namely Ga(CUR), Ga(DAC), Ga(bDHC), by various tumour cell lines was compared with the uptake of the same compounds by normal human lymphocytes by flow cytometry using the intrinsic fluorescence of the curcuminoids. Ga(CUR), and particularly Ga(DAC), showed a higher uptake by colorectal carcinoma (HT29) and lymphoma (K562) cell lines than lymphocytes, while the uptake of Ga(bDHC) was higher in lymphocytes than in all the other cell lines. Based on the fluorescence data, Gallium-68 labelled complexes were then tested in HT29 cell line. Ga(DAC) showed the highest uptake by HT29 cells (higher internalization with a lower externalization) and the highest affinity. The obtained results are promising and the findings foster further investigation on the development of curcumin-metal-based radiopharmaceuticals.
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http://dx.doi.org/10.1016/j.jinorgbio.2017.05.002DOI Listing
August 2017

The influence of coping strategies and behavior on the physiological response to social stress in women: The role of age and menstrual cycle phase.

Physiol Behav 2017 03 15;170:37-46. Epub 2016 Dec 15.

Laboratory of Social Cognitive Neuroscience, University of Valencia, Valencia, Spain.

There is information indicating that the variations induced by the menstrual cycle may influence the capacity of young women to respond to stress. The physiological response to stress changes across the stages of the lifespan; however, in spite of the great increase in life expectancy, the way women react after menopause, a period characterized by a dramatic decline in sex hormones, has not been sufficiently studied. The main objective of the study was to examine the capacity to respond to and recover from an acute social stressor in post-menopausal women compared to young women. The second objective was to investigate the consequences of behavior on the self-regulatory systems. We measured behavior, cortisol, and heart rate during a speaking task in front of a committee in sixty-seven women: 36 post-menopausal and 31 pre-menopausal (follicular group n=14; luteal group n=17). No differences in heart rate reactivity between three groups were found. Post-menopausal women showed less cortisol reactivity to stress; they also displayed a higher percentage of Gestures during the speaking task, reflecting a clearer pattern of active coping compared to the young women. In post-menopausal women, behaviors that reflect active coping strategies were related to better autonomic regulation. By contrast, in pre-menopausal women, cortisol changes seemed to be modulated by passive and reactive behaviors such as Submission and Assertion. These results emphasize the importance of considering age and Hormonal Status in coping processes, including reactivity and recovery from stressful situations.
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http://dx.doi.org/10.1016/j.physbeh.2016.12.011DOI Listing
March 2017

Affinity of (nat/68)Ga-Labelled Curcumin and Curcuminoid Complexes for β-Amyloid Plaques: Towards the Development of New Metal-Curcumin Based Radiotracers.

Int J Mol Sci 2016 Sep 6;17(9). Epub 2016 Sep 6.

Nuclear Medicine Unit, Oncology and Advanced Technologies Department, Arcispedale Santa Maria Nuova-IRCCS, 42123 Reggio Emilia, Italy.

Curcumin derivatives labelled with fluorine-18 or technetium-99m have recently shown their potential as diagnostic tools for Alzheimer's disease. Nevertheless, no study by exploiting the labelling with gallium-68 has been performed so far, in spite of its suitable properties (positron emitter, generator produced radionuclide). Herein, an evaluation of the affinity for synthetic β-amyloid fibrils and for amyloid plaques of three (nat/68)Ga-labelled curcumin analogues, namely curcumin curcumin (CUR), bis-dehydroxy-curcumin (bDHC) and diacetyl-curcumin (DAC), was performed. Affinity and specificity were tested in vitro on amyloid synthetic fibrils by using gallium-68 labelled compounds. Post-mortem brain cryosections from Tg2576 mice were used for the ex vivo visualization of amyloid plaques. The affinity of (68)Ga(CUR)₂⁺, (68)Ga(DAC)₂⁺, and (68)Ga(bDHC)₂⁺ for synthetic β-amyloid fibrils was moderate and their uptake could be observed in vitro. On the other hand, amyloid plaques could not be visualized on brain sections of Tg2576 mice after injection, probably due to the low stability of the complexes in vivo and of a hampered passage through the blood-brain barrier. Like curcumin, all (nat/68)Ga-curcuminoid complexes maintain a high affinity for β-amyloid plaques. However, structural modifications are still needed to improve their applicability as radiotracers in vivo.
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http://dx.doi.org/10.3390/ijms17091480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037758PMC
September 2016

Skin dose saving of the staff in 90Y/177Lu peptide receptor radionuclide therapy with the automatic dose dispenser.

Nucl Med Commun 2016 Oct;37(10):1046-52

aMedical Physics Unit bNuclear Medicine Unit, Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia cDepartment of Industrial Engineering, University of Bologna, Bologna, Italy.

Objective: When handling Y-labelled and Lu-labelled radiopharmaceuticals, skin exposure is mainly due to β-particles. This study aimed to investigate the equivalent dose saving of the staff when changing from an essentially manual radiolabelling procedure to an automatic dose dispenser (ADD).

Materials And Methods: The chemist and physician were asked to wear thermoluminescence dosimeters on their fingertips to evaluate the quantity of Hp(0.07) on the skin. Data collected were divided into two groups: before introducing ADD (no ADD) and after introducing ADD.

Results: For the chemist, the mean values (95th percentile) of Hp(0.07) for no ADD and ADD are 0.030 (0.099) and 0.019 (0.076) mSv/GBq, respectively, for Y, and 0.022 (0.037) and 0.007 (0.023) mSv/GBq, respectively, for Lu. The reduction for ADD was significant (t-test with P<0.05) for both isotopes. The relative differences before and after ADD collected for every finger were treated using the Wilcoxon test, proving a significantly higher reduction in extremity dose to each fingertip for Lu than for Y (P<0.05). For the medical staff, the mean values of Hp(0.07) (95th percentile) for no ADD and ADD are 0.021 (0.0762) and 0.0143 (0.0565) mSv/GBq, respectively, for Y, and 0.0011 (0.00196) and 0.0009 (0.00263) mSv/GBq, respectively, for Lu. The t-test provided a P-value less than 0.05 for both isotopes, making the difference between ADD and no ADD significant.

Conclusion: ADD positively affects the dose saving of the chemist in handling both isotopes. For the medical staff not directly involved with the introduction of the ADD system, the analysis shows a learning curve of the workers over a 5-year period. Specific devices and procedures allow staff skin dose to be limited.
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http://dx.doi.org/10.1097/MNM.0000000000000548DOI Listing
October 2016

Post-Synthesis Incorporation of ⁶⁴Cu in CuS Nanocrystals to Radiolabel Photothermal Probes: A Feasible Approach for Clinics.

J Am Chem Soc 2015 Dec 25;137(48):15145-51. Epub 2015 Nov 25.

Istituto Italiano di Tecnologia , Via Morego 30, 16163, Genova, Italy.

We report a simple method for the incorporation of Cu(I) or (64)Cu(I) radionuclides in covellite nanocrystals (CuS NCs). After the in situ reduction of Cu(II) or (64)Cu(II) ions by ascorbic acid, their incorporation in PEG-coated CuS NCs takes place at room temperature. In all the reaction steps, the stability of the NCs under physiological conditions was ensured. The copper incorporation reaction could also take place on CuS NCs bearing biotin molecules at their surface, with no detrimental effects on the specific binding affinity of the NCs toward streptavidin after incorporation. At low loading of Cu ions, the strong near-infrared (NIR) absorption band of the starting CuS NCs was essentially preserved, which allowed for efficient plasmonic photothermal therapy. The combined presence in the NCs of (64)Cu ions, well suitable for positron emission tomography, and of free carriers responsible for the NIR absorption, should enable their theranostic use as radiotracers and as photothermal probes in tumor ablation treatments. Moreover, the simplicity of the preparation scheme, which involves the use of radioactive species only as a last step, makes the protocol easily transferable to the clinical practice.
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http://dx.doi.org/10.1021/jacs.5b07973DOI Listing
December 2015

Development of a simple kit-based method for preparation of pharmaceutical-grade ⁶⁸Ga-DOTATOC.

Nucl Med Commun 2015 May;36(5):502-10

Nuclear Medicine Unit, Oncology and Advanced Technologies Department, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.

Introduction: The use of germanium-68 (⁶⁸Ge)/gallium-68 (⁶⁸Ga) generators is still limited when compared with the ⁹⁹Mo/⁹⁹mTc counterpart, mainly because of the absence of commercial kits and a kit-based method for preparing Ga-labelled radiopharmaceuticals in a reliable way. The present study aimed to develop and optimize a reliable direct labelling of DOTATOC with ⁶⁸Ga through a kit-based approach.

Materials And Methods: A fraction of the eluate of two different ⁶⁸Ge/⁶⁸Ga generators was directly injected into a vial prefilled with precursor, buffer and scavenger (the prototype of a potential lyophilized kit). The vial was directly warmed to 100°C and then buffered with a 1.5 mol/l sodium ascorbate solution. The parameters influencing the reaction were studied and optimized. The efficacy of the method in terms of incorporation yield and quality of the final radiotracer was compared with preparations performed with two commercial automatic synthesizers by applying the tests prescribed in the European Pharmacopeia monograph for ⁶⁸Ga-DOTATOC.

Results: Under optimal conditions, the overall radiochemical yields of the kit-based process were 73±4 and 69±3% not decay-corrected for the IGG100 and itG generator, respectively. The radiochemical purity was 95±3% and the preparations were compliant with all specifications given in the pharmacopoeia monograph.

Conclusion: The feasibility of a kit-based approach for the preparation of ⁶⁸Ga-DOTATOC was proved and a first home-made version of a putative lyophilized kit was proposed.
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http://dx.doi.org/10.1097/MNM.0000000000000275DOI Listing
May 2015

Synthesis and characterization of (68)Ga-labeled curcumin and curcuminoid complexes as potential radiotracers for imaging of cancer and Alzheimer's disease.

Inorg Chem 2014 May 25;53(10):4922-33. Epub 2014 Apr 25.

Nuclear Medicine Unit, Oncology and Advanced Technologies Department, IRCCS-Arcispedale Santa Maria Nuova , Reggio Emilia, Italy.

Curcumin (CUR) and curcuminoids complexes labeled with fluorine-18 or technetium-99m have recently shown their potential as diagnostic tools for Alzheimer's disease. Gallium-68 is a positron-emitting, generator-produced radionuclide, and its properties can be exploited in situ in medical facilities without a cyclotron. Moreover, CUR showed a higher uptake in tumor cells compared to normal cells, suggesting potential diagnostic applications in this field. In spite of this, no studies using labeled CUR have been performed in this direction, so far. Herein, (68)Ga-labeled complexes with CUR and two curcuminoids, namely diacetyl-curcumin (DAC) and bis(dehydroxy)curcumin (bDHC), were synthesized and characterized by means of experimental and theoretical approaches. Moreover, a first evaluation of their affinity to synthetic β-amyloid fibrils and uptake by A549 lung cancer cells was performed to show the potential application of these new labeled curcuminoids in these diagnostic fields. The radiotracers were prepared by reacting (68)Ga(3+) obtained from a (68)Ge/(68)Ga generator with 1 mg/mL curcuminoids solutions. Reaction parameters (precursor amount, reaction temperature, and pH) were optimized to obtain high and reproducible radiochemical yield and purity. Stoichiometry and formation of the curcuminoid complexes were investigated by matrix-assisted laser desorption ionization time-of-flight mass spectrometry, NMR, ultraviolet-visible, and fluorescence spectroscopy on the equivalent (nat)Ga-curcuminoids (nat = natural) complexes, and their structure was computed by theoretical density functional theory calculations. The analyses evidenced that CUR, DAC, and bDHC were predominantly in the keto-enol form and attested to Ga(L)2(+) species formation. Identity of the (68)Ga(L)2(+) complexes was confirmed by coelution with the equivalent (nat)Ga(L)2(+) complexes in ultrahigh-performance liquid chromatography analyses.(68)Ga(CUR)2(+), (68)Ga(DAC)2(+), and (68)Ga(bDHC)2(+) were highly (87 ± 4, 90 ± 1%) and moderately (48 ± 2%), respectively, retained by synthetic β-amyloid fibrils in vitro. All the Ga-curcuminoid complexes showed an uptake in A549 lung cancer cells, at least equivalent to the respective free curcuminoids, confirming potential applications as cancer-detecting radiotracers.
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http://dx.doi.org/10.1021/ic403113zDOI Listing
May 2014

Influence of different chelators on the radiochemical properties of a 68-Gallium labelled bombesin analogue.

Nucl Med Biol 2014 Jan 31;41(1):24-35. Epub 2013 Oct 31.

Nuclear Medicine Unit, Oncology and Advanced Technologies Department, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. Electronic address:

Unlabelled: The radiolabelled bombesin analogue AMBA shows high potential for diagnosis and treatment of prostate and breast cancer, but the influence of different chelators, which differ in terms of radiochemical reactivity and stability, have not been explored so far. In order to find the best suitable chelator for labelling of AMBA, we synthesized AMBA analogues linked to the most commonly used chelators DOTA, NOTA and NODAGA and compared their reactivity and stability after labelling with 68-Gallium.

Methods: For the synthesis of DO3A-, NO2A- and NODAGA-AMBA, a solid-phase synthesis approach was used. The influence of concentration, pH and temperature on the radiolabelling was analysed. The in vitro stability of all complexes in saline, human serum, human whole blood and against transchelation and transmetallation was analysed.

Results: The peptides were synthesised in high yield and purity. Purity and identity of products and impurities were confirmed using UHPLC coupled to ESI-MS. Radiolabelling of these peptides was optimal at elevated temperature, although room temperature labelling was reported previously for NOTA and NODAGA chelators. The highest reactivity was observed for NODAGA-AMBA. On preparation of NO2A-AMBA, the formation of a by-product was detected with HPLC. More detailed analysis revealed the formation of an isomer with the same mass to charge ratio which led to the conclusion that a coordination isomer was formed. All complexes showed high stability in saline, human serum or when challenged with DTPA, transferrin and varying metals (Fe(3+), Cu(2+), Zn(2+)). Conversely, the stability in human blood was low, and varying metabolites were detected and identified by ESI-MS.

Conclusion: All three precursors are available in high yields suitable for routine production. NODAGA-AMBA showed the most favoured features when labelled with 68-gallium, but a further comparison in vivo should be performed in order to confirm the superior features found in vitro.
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http://dx.doi.org/10.1016/j.nucmedbio.2013.08.010DOI Listing
January 2014
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