Dataset Information

A Bronsted Acidic Gallium Hydride: Facile Interconversion of NNNN-Macrocycle Supported [Ga^I ]⁺ and [Ga^III H]².

ABSTRACT: Protonolysis of [Cp*M] (M=Ga, In, Tl) with [(Me₄ TACD)H][BAr₄ ^Me ] (Me₄ TACD=N,N',N'',N'''-tetramethyl-1,4,7,10-tetraazacyclododecane; [BAr₄ ^Me ]^- =[B{C₆ H₃ -3,5-(CH₃ )₂ }₄ ]^- ) provided monovalent salts [(Me₄ TACD)M][BAr₄ ^Me ], whereas [Cp*Al]₄ yielded trivalent [(Me₄ TACD)AlH][BAr₄ ^Me ]₂ . Protonation of [(Me₄ TACD)Ga][BAr₄ ^Me ] with [Et₃ NH][BAr₄ ^Me ] gave an unusually acidic (pK_a (CH₃ CN)=24.5) gallium(III) hydride dication [(Me₄ TACD)GaH][BAr₄ ^Me ]₂ . Deprotonation with IMe₄ (1,3,4,5-tetramethyl-imidazol-ylidene) returned [(Me₄ TACD)Ga][BAr₄ ^Me ]. These reversible processes occur with formal two-electron oxidation and reduction of gallium. DFT calculations suggest that gallium(I) protonation is facilitated by strong coordination of the tetradentate ligand, which raises the HOMO energy. High nuclear charge of [(Me₄ TACD)GaH]²⁺ facilitates hydride-to-metal charge transfer during deprotonation. Attempts to prepare a gallium(III) dihydride cation resulted in spontaneous dehydrogenation to [(Me₄ TACD)Ga]⁺ .

SUBMITTER: Morris LJ

PROVIDER: S-EPMC9304309 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundProstate-specific membrane antigen (PSMA) is expressed in the microvasculature of thyroid cancer. This suggests the potential use of PSMA as a diagnostic agent in patients with aggressive forms of thyroid cancer. The purpose of the current study was to determine the feasibility and utility of [68Ga]Ga-PSMA-11 PET/MRI in thyroid cancer patients.MethodsEligible patients for this prospective pilot study were adults with a history of pathology-proven thyroid cancer who had abnormal radiotracer uptake on an 2-[18F]FDG PET and/or 131I scintigraphy performed in the 12 months prior to study enrollment. Patients underwent a [68Ga]Ga-PSMA-11 PET/MRI, and comparison was made to the prior qualifying 2-[18F]FDG PET CT/MRI for lesion location and relative intensity.ResultsTwelve patients underwent [68Ga]Ga-PSMA-11 PET/MRI, one of which was excluded from analysis due to debulking surgery prior to the PSMA PET. Of the remaining patients, 7/11 had differentiated disease (3 papillary, 2 follicular, 2 Hurthle cell) and 4/11 had dedifferentiated disease (2 poorly differentiated papillary, 2 anaplastic). Out of 43 lesions, 41 were visually 2-[18F]FDG positive (uptake greater than background, detection rate 95.3%) and 28 were PSMA positive (uptake greater than background, detection rate 65.1%). Uptake was heterogeneous between patients, and in some cases within patients. 3/11 patients (1 poorly differentiated papillary, 2 follicular) had PSMA uptake which was greater than FDG uptake. For the remaining 8 patients, 2-[18F]FDG uptake was greater than PSMA. Using one eligibility guideline in the prostate cancer literature for PSMA radioligand therapy (RLT), 8/11 could be considered eligible for possible future PSMA RLT. This was not predictable based on thyroid cancer subtype.Conclusions[68Ga]Ga-PSMA-11 PET demonstrated lower detection rate when compared to 2-[18F]FDG PET for thyroid cancer lesion visualization. Thyroid cancer subtype alone may not be sufficient to predict PSMA uptake, and radiotracer uptake may vary between patients and even within patients.

Project description:Introduction[68Ga]Ga-P15-041 ([68Ga]Ga-HBED-CC-BP) is a novel bone-seeking PET radiotracer that can be generator-produced. We undertook a Phase 0/I clinical trial to assess its potential for imaging bone metastases in prostate cancer including assessment of radiotracer biodistribution and dosimetry.MethodsSubjects with prostate cancer and known or suspected osseous metastatic disease were enrolled into one of two arms: dosimetry or dynamic. Dosimetry was performed with 6 whole body PET acquisitions and urine collection spanning 3 h; normal organ dosimetry was calculated using OLINDA/EXM. Dynamic imaging included a 60 min acquisition over a site of known or suspected disease followed by two whole body scans. Bootstrapping and subsampling of the acquired list-mode data were conducted to recommend image acquisition parameters for future clinical trials.ResultsUp to 233 MBq (6.3 mCi) of [68Ga]Ga-P15-041 was injected into 12 enrolled volunteers, 8 in dosimetry and 4 in dynamic cohorts. Radiotracer accumulated in known bone lesions and cleared rapidly from blood and soft tissue. The highest individual organ dose was 0.135 mSv/MBq in the urinary bladder wall. The average effective dose was 0.0173 ± 0.0036 mSv/MBq. An average injected activity of 166.5 MBq (4.5 mCi) resulted in absorbed dose estimates of 22.5 mSv to the urinary bladder wall, 8.2 mSv to the kidneys, and an effective dose of 2.9 mSv. Lesion signal to noise ratios on images generated from subsampled data were significantly higher for injected activities above 74 MBq (2 mCi) and were also significantly higher for imaging at 90 min than at 180 min post-injection.ConclusionsDosimetry estimates are acceptable and [68Ga]Ga-P15-041 uptake characteristics in patients with confirmed bone metastases support its continued development.Advances in knowledge and implications for patient careUse of [68Ga]Ga-P15-041 would not require cyclotron infrastructure for manufacturing and distribution, allowing for improved patient access to a promising PET bone imaging agent.

Dataset Information

A Bronsted Acidic Gallium Hydride: Facile Interconversion of NNNN-Macrocycle Supported [Ga^I ]⁺ and [Ga^III H]².

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

A Bronsted Acidic Gallium Hydride: Facile Interconversion of NNNN-Macrocycle Supported [GaI ]+ and [GaIII H]2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

A Bronsted Acidic Gallium Hydride: Facile Interconversion of NNNN-Macrocycle Supported [Ga^I ]⁺ and [Ga^III H]².