In Vitro and In Vivo Characterization of an <sup>18</sup>F-AlF-Labeled PSMA Ligand for Imaging of PSMA-Expressing Xenografts

Lütje, Susanne; Franssen, Gerben M.; Herrmann, Ken; Boerman, Otto C.; Rijpkema, Mark; Gotthardt, Martin; Heskamp, Sandra

doi:10.2967/jnumed.118.218941

Cited by 23 publications

(30 citation statements)

References 19 publications

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“…In addition, the product presented in vivo a bone uptake associated with instability of the compound. (Lütje et al 2017 ). Nevertheless E. Al-Momani et al (Al-Momami et al 2017 ) reported that the stability of the radiopharmaceutical was highly dependent of the formulation conditions, being stable in saline solution with 1% of ethanol or acetate buffer pH 6, and not stable in ethanol 10%/PBS.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform

Giglio

Zeni

Savio

et al. 2018

EJNMMI radiopharm. chem.

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BackgroundOverexpression of prostatic membrane antigen (PSMA) is associated with the progression and prognosis of prostate cancer. There are numerous studies using this peptide with the 68Ga radionuclide. Previous methods to synthetize 18F–labeled PSMA ligands with complexes [18F]AlF2+ have been achieved. However, these reported syntheses were performed manually, using small volumes. Therefore it is only possible to have the radiopharmaceutical on a small scale, for use in preclinical studies. 18F–labelled tracers allow higher doses increasing the number of examined patients. In addition, late images can be acquired in the case of uptake in lymph nodes, to discard inflammation. It is important to transfer the manual synthesis to an automatic module, producing a batch of the radiopharmaceutical with high activity in a safe and effective way. The aim of this work was to optimize the labeling of [18F]AlF-[GLU-UREA-LYS(AHX)-HBED-CC] in a Tracerlab FXFN® (GE) platform.ResultsThe labeling up to the reactor corroborates the formation of the complex [18F]AlF-PSMA. After purification by HPLC, the radiopharmaceutical was achieved with a radiochemical purity higher than 90%. The quality control of the final product fulfilled all the requirements in agreement with USP, such as radiochemical purity (greater than 90%) and residual solvents. [18F]AlF-PSMA was obtained with a yield of 18 ± 3% (n = 7), not decay corrected (NCD) starting off from 500 to 2000 mCi the 18F and with a radiochemical purity of 95 ± 3% (n = 7). The product verified stability in the final formulation vial during 4 hs and in human plasma up to 1 h.ConclusionThe proposed method allowed the production of [18F]AlF-PSMA with suitable radiochemical purity in a commercial platform. High activities were achieved, with a simple and robust methodology appropriate for clinical purposes.

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Section: Introductionmentioning

confidence: 99%

Synthesis of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform

Giglio

Zeni

Savio

et al. 2018

EJNMMI radiopharm. chem.

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“…Older, first-generation, 18 F-labeled radiotracers for PSMA including [ 18 F]DCFBC and the phosphonomethyl compound BAY 1075553 will not be the focus of this review of more-recently-developed agents, but we mention them here to acknowledge the important role of such compounds in providing early evidence of the feasibility of imaging PSMA with 18 F-labeled agents 24-30. This review will focus on newer radiotracers including clinical development of a number of agents, such as the clinically established radiotracers [ 18 F]DCFPyL and [ 18 F]PSMA-1007 (Part I) and the recently introduced agents [ 18 F]CTT1057, [ 18 F]-FSU-880, [ 18 F]JK-PSMA-7 and [ 18 F]AlF-PSMA-11 (Part II) 14, 31-35. Figure 1 illustrates the chemical structures of selected 18 F-labeled compounds 32.…”

Section: Introductionmentioning

confidence: 99%

“…While tumor lesions could be appreciated with comparable uptake, [ 18 F]AlF-PSMA-11 demonstrated lower renal accumulation, which in turn renders this novel 18 F-labeled agent as an attractive compound for detection of small lesions close to the urinary tract. However, as a drawback, [ 18 F]AlF-PSMA-11 demonstrated a time-dependent increase of radiotracer uptake in the bone, and such defluorination may influence the accuracy of lesion detection in the skeleton 35. The favorable binding affinities to PCa has also been proven by investigating PSMA-high LNCaP vs. PSMA-low PC3 tumors, showing a 24-fold higher uptake for [ 18 F]AlF-PSMA-11 in the high LNCaP tumors in C57BL6 mice 82.…”

Section: Part Ii: Recently Introduced 18f-labeled Radiotracersmentioning

confidence: 99%

“…[ 18 F]DCFPyL has very low hepatic uptake, which allows for the detection of small liver lesions even when cross-sectional correlates cannot be appreciated 14 or may be of value in later stages of disease 51. [ 18 F]PSMA-1007 and [ 18 F]AlF-PSMA-11 have very low radiotracer accumulation in the urinary system, which renders these imaging agents an attractive alternative to identify small lesions in the pelvis or for local recurrence 35, 69. [ 18 F]JK-PSMA-7 may have higher target-to-background ratios and imaging acutance compared to [ 68 Ga]PSMA compounds as suggested by pre-clinical and clinical data 34, 81.…”

Section: Part Ii: Recently Introduced 18f-labeled Radiotracersmentioning

confidence: 99%

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¹⁸F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

Werner¹,

Derlin²,

Lapa³

et al. 2020

Theranostics

132

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Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with 68Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from 68Ga- to 18F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite 68Ge/68Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, 18F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, 18F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging 18F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available 18F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.

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“…A comparative study between two PSMA-11 derivatives has recently been conducted by Lütje et al [100]. In contrast to [ 68 Ga]Ga-PSMA-11, [ 18 F]AlF-PSMA-11 appeared to be unstable in water (64.5% radiochemical purity immediately after purification and 52.7% at 2 h post-purification) but remained relatively stable in 25 mM NH 4 OAc pH 6.9 (94.7% radiochemical purity at 2 h post-purification).…”

Section: Overview Of [18f]alf-labeled Molecules Conjugated To Chelmentioning

confidence: 99%

A Comprehensive Review of Non-Covalent Radiofluorination Approaches Using Aluminum [18F]fluoride: Will [18F]AlF Replace 68Ga for Metal Chelate Labeling?

et al. 2019

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Due to its ideal physical properties, fluorine-18 turns out to be a key radionuclide for positron emission tomography (PET) imaging, for both preclinical and clinical applications. However, usual biomolecules radiofluorination procedures require the formation of covalent bonds with fluorinated prosthetic groups. This drawback makes radiofluorination impractical for routine radiolabeling, gallium-68 appearing to be much more convenient for the labeling of chelator-bearing PET probes. In response to this limitation, a recent expansion of the 18F chemical toolbox gave aluminum [18F]fluoride chemistry a real prominence since the late 2000s. This approach is based on the formation of an [18F][AlF]2+ cation, complexed with a 9-membered cyclic chelator such as NOTA, NODA or their analogs. Allowing a one-step radiofluorination in an aqueous medium, this technique combines fluorine-18 and non-covalent radiolabeling with the advantage of being very easy to implement. Since its first reports, [18F]AlF radiolabeling approach has been applied to a wide variety of potential PET imaging vectors, whether of peptidic, proteic, or small molecule structure. Most of these [18F]AlF-labeled tracers showed promising preclinical results and have reached the clinical evaluation stage for some of them. The aim of this report is to provide a comprehensive overview of [18F]AlF labeling applications through a description of the various [18F]AlF-labeled conjugates, from their radiosynthesis to their evaluation as PET imaging agents.

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In Vitro and In Vivo Characterization of an ¹⁸F-AlF-Labeled PSMA Ligand for Imaging of PSMA-Expressing Xenografts

Cited by 23 publications

References 19 publications

Synthesis of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform

Synthesis of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform

¹⁸F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

A Comprehensive Review of Non-Covalent Radiofluorination Approaches Using Aluminum [18F]fluoride: Will [18F]AlF Replace 68Ga for Metal Chelate Labeling?

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In Vitro and In Vivo Characterization of an 18F-AlF-Labeled PSMA Ligand for Imaging of PSMA-Expressing Xenografts

Cited by 23 publications

References 19 publications

Synthesis of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform

Synthesis of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand in an automated synthesis platform

18F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

A Comprehensive Review of Non-Covalent Radiofluorination Approaches Using Aluminum [18F]fluoride: Will [18F]AlF Replace 68Ga for Metal Chelate Labeling?

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In Vitro and In Vivo Characterization of an ¹⁸F-AlF-Labeled PSMA Ligand for Imaging of PSMA-Expressing Xenografts

¹⁸F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging