Impact of the molar activity and PSMA expression level on [18F]AlF-PSMA-11 uptake in prostate cancer

Piron, Sarah; Verhoeven, Jeroen; Coster, Emma De; Descamps, Benedicte; Kersemans, Ken; Pieters, Leen; Vral, Anne; Vanhove, Christian; Vos, Filip De

doi:10.1038/s41598-021-02104-6

Cited by 8 publications

(9 citation statements)

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“…Several studies report that larger tumors and limited tumor vasculature may result in significant increases in hypoxia burden and tumor necrosis [ 38 , 76 , 77 , 78 , 79 , 80 ]. The effective molar activity may influence the biodistribution of radioligands by leading to variable degrees of receptor saturation in PSMA-expressing tissues [ 25 , 43 , 44 ]. In the present study, a more than 5-fold decrease in the effective molar activity of 212 Pb-NG001 did not have any effect on tumor and kidney uptake ( Figure S5 ), suggesting that the binding sites were not saturated at the tested ligand amounts.…”

Section: Discussionmentioning

confidence: 99%

“…Another aspect that makes direct comparisons of different radiopharmaceuticals challenging is the use of a range of molar amounts and activities of radioligands. This can lead to variable degrees of receptor saturation in PSMA-expressing tissues, thereby influencing uptake [ 25 , 43 , 44 , 45 ]. Some studies report increased tumor and kidney uptake at increasing effective molar activities (MBq/nmol of ligand) [ 25 , 43 , 44 , 46 , 47 ], whereas others observe no such correlation [ 45 , 48 , 49 ].…”

Section: Introductionmentioning

confidence: 99%

“…This can lead to variable degrees of receptor saturation in PSMA-expressing tissues, thereby influencing uptake [ 25 , 43 , 44 , 45 ]. Some studies report increased tumor and kidney uptake at increasing effective molar activities (MBq/nmol of ligand) [ 25 , 43 , 44 , 46 , 47 ], whereas others observe no such correlation [ 45 , 48 , 49 ]. Thus, it is challenging to interpret how the molar activity of radioligands may impact tumor and kidney accumulation.…”

Section: Introductionmentioning

confidence: 99%

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Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand 212Pb-NG001

Stenberg

Tornes

Nilsen

et al. 2022

Cancers

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This study aimed to determine the influence of cellular PSMA expression, radioligand binding and internalization, and repeated administrations on the therapeutic effects of the PSMA-targeting radioligand 212Pb-NG001. Cellular binding and internalization, cytotoxicity, biodistribution, and the therapeutic efficacy of 212Pb-NG001 were investigated in two human prostate cancer cell lines with different PSMA levels: C4-2 (PSMA+) and PC-3 PIP (PSMA+++). Despite 10-fold higher PSMA expression on PC-3 PIP cells, cytotoxicity and therapeutic efficacy of the radioligand was only 1.8-fold better than for the C4-2 model, possibly explained by lower cellular internalization and less blood-rich stroma in PC-3 PIP xenografts. Mice bearing subcutaneous PC-3 PIP xenografts were treated with 0.2, 0.4, and 0.8 MBq of 212Pb-NG001 that resulted in therapeutic indexes of 2.7, 3.0, and 3.5, respectively. A significant increase in treatment response was observed in mice that received repeated injections compared to the corresponding single dose (therapeutic indexes of 3.6 for 2 × 0.2 MBq and 4.4 for 2 × 0.4 MBq). The results indicate that 212Pb-NG001 can induce therapeutic effects at clinically transferrable doses, both in the C4-2 model that resembles solid tumors and micrometastases with natural PSMA expression and in the PC-3 PIP model that mimics poorly vascularized metastases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand 212Pb-NG001

Stenberg

Tornes

Nilsen

et al. 2022

Cancers

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“…This feature is also highly reliant on the biological half-life of a tracer. Since higher molar activities help reduce receptor saturation and thus improve the diagnostic potential of PSMA-radiotracers [ 19 ], one can wonder if administration of > 100 µg of a PSMA-tracer would not automatically lead to overdosing and increase background signals. In addition, clinical studies indicate that microdosing should be feasible for fluorescent agents [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Feasibility of fluorescence imaging at microdosing using a hybrid PSMA tracer during robot-assisted radical prostatectomy in a large animal model

et al. 2022

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Background With the rise of prostate-specific membrane antigen (PSMA) radioguided surgery, which is performed using a microdosing regime, demand for visual target confirmation via fluorescence guidance is growing. While proven very effective for radiotracers, microdosing approaches the detection limit for fluorescence imaging. Thus, utility will be highly dependent on the tracer performance, the sensitivity of the fluorescence camera used, and the degree of background signal. Using a porcine model the ability to perform robot-assisted radical prostatectomy under fluorescence guidance using the bimodal or rather hybrid PSMA tracer (99mTc-EuK-(SO3)Cy5-mas3) was studied, while employing the tracer in a microdosing regime. This was followed by ex vivo evaluation in surgical specimens obtained from prostate cancer patients. Results T50% blood and T50% urine were reached at 85 min and 390 min, in, respectively, blood and urine. Surgical fluorescence imaging allowed visualization of the prostate gland based on the basal PSMA-expression in porcine prostate. Together, in vivo visualization of the prostate and urinary excretion suggests at least an interval of > 7 h between tracer administration and surgery. Confocal microscopy of excised tissues confirmed tracer uptake in kidney and prostate, which was confirmed with PSMA IHC. No fluorescence was detected in other excised tissues. Tumor identification based on ex vivo fluorescence imaging of human prostate cancer specimens correlated with PSMA IHC. Conclusion Intraoperative PSMA-mediated fluorescence imaging with a microdosing approach was shown to be feasible. Furthermore, EuK‐(SO3)Cy5‐mas3 allowed tumor identification in human prostate samples, underlining the translational potential of this novel tracer. Trial registration Approval for use of biological material for research purposes was provided by the Translational Research Board of the Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital (NKI-AvL) under reference IRBm19-273 (22/10/2019).

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“…After the last scan, two mice/cell line xenografts were sacrificed and tumors were collected for immunohistochemical (IHC) evaluation of the PSMA expression levels as previously reported 28 . In short, sections were taken from the center of the tumor sample and stained using Haematoxylin/Eosin, incubated with a primary PSMA antibody (1:400, 2 h, ab133579, Abcam) and counterstained using Haematoxylin (Mayer).…”

Section: Methodsmentioning

confidence: 99%

Preclinical comparative study of [18F]AlF-PSMA-11 and [18F]PSMA-1007 in varying PSMA expressing tumors

Piron

Verhoeven

Courtyn

et al. 2022

Sci Rep

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A wide variety of 18F-labeled PSMA-targeting PET radiotracers have been developed, including [18F]AlF-PSMA-11. As there is only limited data on the comparison with other 18F-labeled PSMA PET tracers, a comparative preclinical study between [18F]AlF-PSMA-11 and [18F]PSMA-1007 was conducted. Mice with varying PSMA expressing tumors (C4-2, 22Rv1 and PC-3, each n = 5) underwent two PET/CT scans with both [18F]AlF-PSMA-11 and [18F]PSMA-1007. Ten additional mice bearing C4-2 xenografts were subjected to ex vivo biodistribution with either [18F]AlF-PSMA-11 (n = 5) or [18F]PSMA-1007 (n = 5). Absolute SUVmean and SUVmax values were significantly higher for [18F]PSMA-1007 scans in both C4-2 tumors (p < 0.01) and 22Rv1 tumors (p < 0.01). In C4-2 xenograft bearing mice, the tumor-to-organ ratios did not significantly differ between [18F]AlF-PSMA-11 and [18F]PSMA-1007 for liver, muscle, blood and salivary glands (p > 0.05). However, in 22Rv1 xenograft bearing mice, all tumor-to-organ ratios were higher for [18F]AlF-PSMA-11 (p < 0.01). In healthy organs, [18F]PSMA-1007 uptake was higher in the liver, gallbladder, small intestines and glands. Biodistribution data confirmed the increased uptake in the heart, small intestines and liver with [18F]PSMA-1007. Absolute tumor uptake was higher with [18F]PSMA-1007 in all tumors. Tumor-to-organ ratios did not differ significantly in high PSMA expressing tumors, but were higher for [18F]AlF-PSMA-11 in low PSMA expressing tumors. Furthermore, [18F]PSMA-1007 showed higher uptake in healthy organs.

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Impact of the molar activity and PSMA expression level on [18F]AlF-PSMA-11 uptake in prostate cancer

Cited by 8 publications

References 32 publications

Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand 212Pb-NG001

Factors Influencing the Therapeutic Efficacy of the PSMA Targeting Radioligand 212Pb-NG001

Feasibility of fluorescence imaging at microdosing using a hybrid PSMA tracer during robot-assisted radical prostatectomy in a large animal model

Preclinical comparative study of [18F]AlF-PSMA-11 and [18F]PSMA-1007 in varying PSMA expressing tumors

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