Preclinical Evaluation and Pilot Clinical Study of Al<sup>18</sup>F-PSMA-BCH for Prostate Cancer PET Imaging

Liu, Teli; Liu, Chen; Xu, Xiaoxia; Liu, Fei; Guo, Xiaoyi; Li, Nan; Wang, Xuejuan; Yang, Jianhua; Yang, Xing; Zhu, Hua; Yang, Zhi

doi:10.2967/jnumed.118.221671

Cited by 66 publications

(48 citation statements)

References 43 publications

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“…In vitro characterization of 18 19 and Sanchez-Crespo et al (27.05 nM in LNCaP cells) 20 . The recently evaluated 18 F-PSMA-BCH demonstrated a comparable K d value of 2.90 ± 0.83 nM in 22Rv1 cells 21 .…”

Section: Discussionmentioning

confidence: 78%

Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice

Piron

Verhoeven

Descamps

et al. 2020

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Recently, a 18F-labeled derivative of the widely used 68Ga-PSMA-11 was developed for PET imaging of prostate cancer. Although 18F-PSMA-11 has already been evaluated in a Phase I and Phase II clinical trial, preclinical evaluation of this radiotracer is important for further understanding its dynamic behavior. Saturation binding experiments were conducted by incubation of LNCaP cells with 18F-PSMA-11 or 68Ga-PSMA-11 for 1 h, followed by determination of the specific and aspecific binding. Mice bearing LNCaP or PC-3 xenografts each received ± 3.7 MBq 18F-PSMA-11 and 68Ga-PSMA-11 followed by dynamic acquisition of 2.5 h as well as ± 15 MBq 18F-FDG followed by static acquisition at 1 h post injection (p.i.). Uptake was evaluated by comparison of uptake parameters (SUVmean, SUVmax, TBRmean and TBRmax). Mice underwent ex vivo biodistribution where 18F-PSMA-11 activity was measures in excretory organs (kidneys, bladder and liver) as well as bone fragments (femur, humerus, sternum and skull) to evaluate bone uptake. The dissociation constant (Kd) of 18F-PSMA-11 and 68Ga-PSMA-11 was 2.95 ± 0.87 nM and 0.49 ± 0.20 nM, respectively. Uptake parameters were significantly higher in LNCaP compared to PC-3 xenografts for both 18F-PSMA-11 and 68Ga-PSMA-11, while no difference was found for 18F-FDG uptake (except for SUVmax). Tumor uptake of 18F-PSMA-11 showed a similar trend over time as 68Ga-PSMA-11, although all uptake parameter curves of the latter were considerably lower. When comparing early (60 min p.i.) to delayed (150 min p.i.) imaging for both radiotracers individually, TBRmean and TBRmax were significantly higher at the later timepoint, as well as the SUVmax of 68Ga-PSMA-11. The highest %ID/g was determined in the kidneys (94.0 ± 13.6%ID/g 1 h p.i.) and the bladder (6.48 ± 2.18%ID/g 1 h p.i.). No significant increase in bone uptake was seen between 1 and 2 h p.i. Both radiotracers showed high affinity for the PSMA receptor. Over time, all uptake parameters were higher for 18F-PSMA-11 compared to 68Ga-PSMA-11. Delayed imaging with the latter may improve tumor visualization, while no additional benefits could be found for late 18F-PSMA-11 imaging. Ex vivo biodistribution demonstrated fast renal clearance of 18F-PSMA-11 as well as no significant increase in bone uptake.

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Section: Discussionmentioning

confidence: 78%

Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice

Piron

Verhoeven

Descamps

et al. 2020

Sci Rep

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“…However, in contrast to humans, mice have very low to no PSMA expression in the prostate and jejunum. Furthermore, despite the high PSMA expression in murine salivary glands, biodistribution assays with various PSMA-targeting tracers did not show any, or very low salivary gland uptake, while renal uptake is similar or even higher in mice compared to humans [113,114,115,116]. This difference in PSMA expression might be explained by the difference in PSMA amino acid sequence between humans and mice (91% similarity).…”

Section: Protection Of Psma Expressing Kidneys and Salivary Glandsmentioning

confidence: 91%

The Future of PSMA-Targeted Radionuclide Therapy: An Overview of Recent Preclinical Research

et al. 2019

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Prostate specific membrane antigen (PSMA) has become a major focus point in the research and development of prostate cancer (PCa) imaging and therapeutic strategies using radiolabeled tracers. PSMA has shown to be an excellent target for PCa theranostics because of its high expression on the membrane of PCa cells and the increase in expression during disease progression. Therefore, numerous PSMA-targeting tracers have been developed and (pre)clinically studied with promising results. However, many of these PSMA-targeting tracers show uptake in healthy organs such as the salivary glands, causing radiotoxicity. Furthermore, not all patients respond to PSMA-targeted radionuclide therapy (TRT). This created the necessity of additional preclinical research studies in which existing tracers are reevaluated and new tracers are developed in order to improve PSMA-TRT by protecting the (PSMA-expressing) healthy organs and improving tumor uptake. In this review we will give an overview of the recent preclinical research projects regarding PCa-TRT using PSMA-specific radiotracers, which will give an indication of where the PSMA-TRT research movement is going and what we can expect in future clinical trials.

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“…Recently, Liu et al reported a novel [ 18 F]AlF-labeled PSMA ligand, [ 18 F]AlF-PSMA-BCH (Figure 8), evaluated through a preclinical study and a pilot clinical study on 11 newly diagnosed prostate cancer patients [101]. [ 18 F]AlF-PSMA-BCH was synthesized in modest RCY (32.2 ± 4.5%), with moderate molar activity (13.2 to 18.9 GBq/µmol, that could probably be increased by automated synthesis) but with a high radiochemical purity (>99%).…”

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

confidence: 99%

“…As stated before, [ 18 F]AlF-PSMA-BCH was evaluated on 11 patients with prostate cancer and displayed good detectability of tumor lesions with reasonable radiation exposure [101]. Nonetheless, the two [ 18 F]AlF-labeled tracers that were the most studied in man are NOTA-PRGD 2 derivatives alfatide I and alfatide II.…”

Section: Current Clinical Use Of [18f]alf-labeled Biomoleculesmentioning

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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Preclinical Evaluation and Pilot Clinical Study of Al¹⁸F-PSMA-BCH for Prostate Cancer PET Imaging

Cited by 66 publications

References 43 publications

Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice

Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice

The Future of PSMA-Targeted Radionuclide Therapy: An Overview of Recent Preclinical Research

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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Preclinical Evaluation and Pilot Clinical Study of Al18F-PSMA-BCH for Prostate Cancer PET Imaging

Cited by 66 publications

References 43 publications

Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice

Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice

The Future of PSMA-Targeted Radionuclide Therapy: An Overview of Recent Preclinical Research

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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Preclinical Evaluation and Pilot Clinical Study of Al¹⁸F-PSMA-BCH for Prostate Cancer PET Imaging