Hallmarks in prostate cancer imaging with Ga68-PSMA-11-PET/CT with reference to detection limits and quantitative properties

Sánchez-Crespo, Alejandro; Jussing, Emma; Björklund, Andreas; Tamm, Katja Pokrovskaja

doi:10.1186/s13550-018-0378-4

Cited by 9 publications

(13 citation statements)

References 25 publications

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“…(4.3 ± 0.8 nM in LNCaP cells) 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: 99%

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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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: 99%

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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“…where β 0 and β 1 refer to the logistic regression coefficients and x denotes the cell number [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…where β 0 and β 1 refer to the logistic regression coefficients and x denotes the cell number [18]. Prior to logistic regression, binary classification of PET/CT and PET/MR image CNR was performed using the Rose criterion (i.e., classification using a threshold of CNR = 5).…”

Section: Pet Image Analysismentioning

confidence: 99%

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Detection limit of 89Zr-labeled T cells for cellular tracking: an in vitro imaging approach using clinical PET/CT and PET/MRI

et al. 2020

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Purpose: Tracking cells in vivo using imaging can provide non-invasive information to understand the pharmacology, efficacy, and safety of novel cell therapies. Zirconium-89 (t 1/2 = 78.4 h) has recently been used to synthesize [ 89 Zr]Zr(oxinate) 4 for cell tracking using positron emission tomography (PET). This work presents an in vitro approach to estimate the detection limit for in vivo PET imaging of Jurkat T cells directly labeled with [ 89 Zr]Zr(oxinate) 4 utilizing clinical PET/CT and PET/MRI. Methods: Jurkat T cells were labeled with varying concentrations of [ 89 Zr]Zr(oxinate) 4 to generate different cell-specific activities (0.43-31.91 kBq/10 6 cells). Different concentrations of labeled cell suspensions (10 4 , 10 5 , and 10 6 cells) were seeded on 6-well plates and into a 3 × 3 cubic-well plate with 1 cm 3 cubic wells as a gel matrix. Plates were imaged on clinical PET/ CT and PET/MRI scanners for 30 min. The total activity in each well was determined by drawing volumes of interest over each well on PET images. The total cell-associated activity was measured using a well counter and correlated with imaging data. Simulations for non-specific signal were performed to model the effect of non-specific radioactivity on detection. Results: Using this in vitro model, the lowest cell number that could be visualized on 6-well plate images was 6.8 × 10 4 , when the specific activity was 27.8 kBq/10 6 cells. For the 3 × 3 cubic-well, a plate of 3.3 × 10 4 cells could be detected on images with a specific activity of 15.4 kBq/10 6 cells. Conclusion: The results show the feasibility of detecting [ 89 Zr]Zr(oxinate) 4-labeled Jurkat T cells on clinical PET systems. The results provide a best-case scenario, as in vivo detection using PET/CT or PET/MRI will be affected by cell number, specific activity per cell, the density of cells within the target volume, and non-specific signal. This work has important implications for cell labeling studies in patients, particularly when using radiosensitive cells (e.g., T cells), which require detection of low cell numbers while minimizing radiation dose per cell.

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“…50 More recently, gallium-68-labeled PSA (Ga68-PSMA-11) PET/CT has emerged as a potential gold standard for PCa diagnosis and follow-up. 51 Since 223 Ra also emits gamma radiation (1.1%; energy range 0.01–1.27 MeV), a bremsstrahlung acquisition using conventional gamma-cameras (high-energy collimator; energy window 80 KeV ±20%) is still possible 4 hours after each administration, if required. This approach may provide biodistribution and staging information as well as restaging in case of unexpected progression.…”

Section: Diagnostic Imaging Related To Ra-223 Therapymentioning

confidence: 99%

Radium-223 for the treatment of bone metastases in castration-resistant prostate cancer: when and why

Gallicchio

Mastrangelo

Nardelli

et al. 2019

Tumori

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Radium-223 dichloride (223Ra) is the first, recently approved, α-particle-emitting radiopharmaceutical for the treatment of patients with bone metastases in castration-resistant prostate cancer (CRPC) and no evidence of visceral metastases. We explored MEDLINE, relevant congresses, and websites for data on 223Ra and prostate cancer therapies, focusing on therapeutic strategies and timing, bone metastases, and diagnostic assessment. 223Ra represents the only bone-targeting agent that has significantly extended patients’ overall survival while reducing pain and symptomatic skeletal events. Unlike other radiopharmaceuticals, such as strontium-89 and samarium-153 EDTMP, 223Ra (11.4-days half-life) has shown a high biological efficiency mainly due to its short penetration range. These features potentially allow reduced bone marrow toxicity and limit undue exposure. 223Ra has been validated under the product name Xofigo® by the US Food and Drug Administration and the European Medicines Agency. Patient selection, management, and treatment sequencing is recommended to be discussed in the context of a multidisciplinary environment, including oncology, urology, nuclear medicine, and radiation therapy physicians. No consensus has been achieved regarding the optimal timing and its administration as single agent or in combination with zoledronic acid or chemotherapy, so far. This review aims to provide a rationale for the use of 223Ra in treating metastases from CRPC, highlighting the crucial role of a multidisciplinary approach, the disputed inclusion and exclusion criteria on the basis of agencies regulations, and the value of diagnostics for therapy assessment.

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Hallmarks in prostate cancer imaging with Ga68-PSMA-11-PET/CT with reference to detection limits and quantitative properties

Cited by 9 publications

References 25 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

Detection limit of 89Zr-labeled T cells for cellular tracking: an in vitro imaging approach using clinical PET/CT and PET/MRI

Radium-223 for the treatment of bone metastases in castration-resistant prostate cancer: when and why

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