Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer

Fuscaldi, Leonardo Lima; Sobral, Danielle Vieira; Durante, Ana Claudia R.; Mendonça, Fernanda F.; Miranda, Ana Cláudia Camargo; Cunha, Marcelo Livorsi da; Malavolta, Luciana; Mejía, Jorge; Barboza, Marlei

doi:10.3390/ph14050385

Cited by 15 publications

(23 citation statements)

References 43 publications

(48 reference statements)

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“…The increased values can be attributed to a more stable 99m Tc-DTPA complex resulting in a new pharmacological profile. Similar results were also reported for 99m Tc-PSMA-11 (40) and 68 Ga-PSMA-11 (41), wherein the log P-value for 99m Tc complex displayed higher lipophilic property as compared to 68 Ga complex.…”

Section: Partition Coefficient Determinationsupporting

confidence: 85%

Bio-Evaluation of 99mTc-Labeled Homodimeric Chalcone Derivative as Amyloid-β-Targeting Probe

et al. 2022

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Chalcone derivatives have been successfully utilized for a range of biological applications and can cross the blood–brain barrier easily. β-amyloid-specific bis-chalcone derivative, 6,9-bis(carboxymethyl)-14-(4-[(E)-3-(4-(dimethylamino)phenyl)acryloyl]phenoxy)-3-(2-[(2-(4-[(E)-3-(4-(dimethylamino)phenyl)acryloyl]phenoxy)ethyl)amino]-2-oxoethyl)-11-oxo-3,6,9,12-tetraazatetradecanoic acid, DT(Ch)2, was analyzed using molecular modeling to explain the binding modes of the ligand with amyloid fibril and monomer followed by 99mTc-complexation in 95% yield and 98.7% efficiency. High-binding specificity of the radiocomplex was established following in vitro evaluation against 100-fold excess of DT(Ch)2. 99mTc–DT(Ch)2 exhibited <3% trans-complexation in human serum after 24 h, indicating high stability. A fast clearance rate in pharmacokinetics studies displayed a biphasic pattern with t1/2(F) = 30 min ± 0.09 and t1/2(S) = 4 h 20 min ± 0.06. In vivo single-photon emission computed tomography (SPECT) imaging in rabbits reiterated the pharmacokinetics data with initially high brain uptake followed by rapid washout. Biodistribution studies confirmed the initial brain uptake as 1.16 ± 0.02% ID/g after 2 min and the brain2min/brain30min ratio was 3.74. Radioactivity distribution in the brain was >40% in the cingulate cortex followed by >25% in the hippocampus, a distribution pattern aligned to Alzheimer’s affected brain regions. Radiocomplex also displayed rapid plasma clearance followed by hepatobolic and renal modes of excretion.

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Section: Partition Coefficient Determinationsupporting

confidence: 85%

Bio-Evaluation of 99mTc-Labeled Homodimeric Chalcone Derivative as Amyloid-β-Targeting Probe

et al. 2022

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“…However, in both cases, at least 50% of the radiopeptides are free to reach the target of interest. Although this approach is technically appropriate to estimate SPB and has been described in the literature [25][26][27], there is the possibility of peptide precipitation within the proteins.…”

Section: Serum Protein Bindingmentioning

confidence: 99%

Comparative Evaluation of Radiochemical and Biological Properties of 131I- and [99mTc]Tc(CO)3-Labeled RGD Analogues Planned to Interact with the αvβ3 Integrin Expressed in Glioblastoma

et al. 2022

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Radiolabeled peptides with high specificity for overexpressed receptors in tumor cells hold great promise for diagnostic and therapeutic applications. In this work, we aimed at comparing the radiolabeling efficiency and biological properties of two different RGD analogs: GRGDYV and GRGDHV, labeled with iodine-131 (131I) and technetium-99m-tricarbonyl complex [99mTc][Tc(CO)3]+. Additionally, we evaluated their interaction with the αvβ3 integrin molecule, overexpressed in a wide variety of tumors, including glioblastoma. Both peptides were chemically synthesized, purified and radiolabeled with 131I and [99mTc][Tc(CO)3]+ using the chloramine-T and tricarbonyl methodologies, respectively. The stability, binding to serum proteins and partition coefficient were evaluated for both radioconjugates. In addition, the binding and internalization of radiopeptides to rat C6 glioblastoma cells and rat brain homogenates from normal animals and a glioblastoma-induced model were assessed. Finally, ex vivo biodistribution studies were carried out. Radiochemical yields between 95–98% were reached for both peptides under optimized radiolabeling conditions. Both peptides were stable for up to 24 h in saline solution and in human serum. In addition, the radiopeptides have hydrophilic characteristics and a percentage of binding to serum proteins around 35% and 50% for the [131I]I-GRGDYV and [99mTc]Tc(CO)3-GRGDHV fragments, respectively. Radiopeptides showed the capacity of binding and internalization both in cell culture (C6) and rat brain homogenates. Biodistribution studies corroborated the results obtained with brain homogenates and confirmed the different binding characteristics due to the exchange of radionuclides and the presence of the tricarbonyl complex. Thereby, the results showed that both radiopeptides might be considered for future clinical applications.

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“…High-performance liquid chromatography (HPLC) coupled with a radio detector is the preferred semi-quantitative method for determining radiochemical purity of [ 177 Lu]Lu-PSMA (Gillings et al 2020 ). HPLC of radiolabeled PSMA-ligands (such as PSMA-I&T, PSMA-I&S, PSMA-I&F, PSMA-11, PSMA-1007, PSMA-617) is almost always performed with a reversed phase C18 column (generally with a pore size between 120 and 300 Å, a length of 150–250 mm, diameter of 3.0–4.6 mm, and a particle size of 3–5 µm, although many different brands are reported), with a gradient of acidified water and acetonitrile as the most common mobile phase (Migliari et al 2017 ; Schottelius et al 2019 ; Wang et al 2018 ; Aalbersberg et al 2020 ; Fuscaldi et al 2014 ; Hooijman et al 2021 ; Iudicello et al 2021 ; Katzschmann et al 2021 ; Ugur et al 2021 ; European Pharmacopoeia 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Quality control of [177Lu]Lu-PSMA preparations using HPLC: effect of sample composition and ligand on recovery

Aalbersberg

Cao

Geluk–Jonker

et al. 2022

EJNMMI radiopharm. chem.

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Background [177Lu]Lu-PSMA is used for the treatment of metastatic castration-resistant prostate cancer. For in-house productions, quality control methods are essential for ensuring product quality, and thus patient safety. During HPLC method development for quality control of [177Lu]Lu-PSMA-I&T, we noticed an unpredictable variability in peak area and height with replicate measurements. After a run, irremovable radioactivity was measured over the whole the length of the HPLC column, with slightly higher activity at the beginning and end of the column. The uniform distribution suggests that [177Lu]Lu-PSMA-I&T interacts with the column. As a result of the interaction, incomplete and variable recovery of injected activity was observed leading to the variability in peak area and height. Therefore the aim of this study was to (1) investigate the effect of sample composition on the interaction of [177Lu]Lu-PSMA-I&T to the HPLC column (measured as recovery, peak area, and peak height), and (2) to compare this with same concentrations of the well-known [177Lu]Lu-PSMA-617. Results Sample composition significantly affects recovery of [177Lu]Lu-PSMA-I&T, leading to a change in peak area and height. Recovery was 24% when diluted with 0.1 mM octreotide, 38% with water, and increased to 95% when diluted with 0.7 mM unlabeled PSMA-I&T. Peak area and height decreased to 26% and 17% when diluted in octreotide and to 41% and 29% when diluted in water, compared to a dilution in PSMA-I&T. Further experiments showed that recovery (and consequently peak area and peak height) reached a plateau of > 99% at concentrations of 0.27 mM and higher. [177Lu]Lu-PSMA-617 also interacts with the HPLC column, leading to lower, but less variable, recovery (9%). The low recovery of [177Lu]Lu-PSMA-617 could not be prevented with addition of unlabeled PSMA-617. Conclusion [177Lu]Lu-PSMA-I&T can undergo an irreversible binding with an HPLC column resulting in a decreased recovery. The recovery is can be highly dependent on sample composition. The addition of a surplus of unlabeled PSMA-I&T leads to an accurate analysis of [177Lu]Lu-PSMA-I&T.

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Standardization of the [68Ga]Ga-PSMA-11 Radiolabeling Protocol in an Automatic Synthesis Module: Assessments for PET Imaging of Prostate Cancer

Cited by 15 publications

References 43 publications

Bio-Evaluation of 99mTc-Labeled Homodimeric Chalcone Derivative as Amyloid-β-Targeting Probe

Bio-Evaluation of 99mTc-Labeled Homodimeric Chalcone Derivative as Amyloid-β-Targeting Probe

Comparative Evaluation of Radiochemical and Biological Properties of 131I- and [99mTc]Tc(CO)3-Labeled RGD Analogues Planned to Interact with the αvβ3 Integrin Expressed in Glioblastoma

Quality control of [177Lu]Lu-PSMA preparations using HPLC: effect of sample composition and ligand on recovery

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