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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarah Piron ◽  
Jeroen Verhoeven ◽  
Emma De Coster ◽  
Benedicte Descamps ◽  
Ken Kersemans ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Preclinical Study ◽  
Radioligand Therapy ◽  
Limited Effect ◽  
Reduce Radiation Exposure ◽  
Molar Activity ◽  
Increasing Trend ◽  
Target Binding ◽  
Specific Membrane ◽  
Psma Expression

AbstractThis two-part preclinical study aims to evaluate prostate specific membrane antigen (PSMA) as a valuable target for expression-based imaging applications and to determine changes in target binding in function of varying apparent molar activities (MAapp) of [18F]AlF-PSMA-11. For the evaluation of PSMA expression levels, male NOD/SCID mice bearing prostate cancer (PCa) xenografts of C4-2 (PSMA+++), 22Rv1 (PSMA+) and PC-3 (PSMA−) were administered [18F]AlF-PSMA-11 with a medium MAapp (20.24 ± 3.22 MBq/nmol). SUVmean and SUVmax values were respectively 3.22 and 3.17 times higher for the high versus low PSMA expressing tumors (p < 0.0001). To evaluate the effect of varying MAapp, C4-2 and 22Rv1 xenograft bearing mice underwent additional [18F]AlF-PSMA-11 imaging with a high (211.2 ± 38.9 MBq/nmol) and/or low MAapp (1.92 ± 0.27 MBq/nmol). SUV values showed a significantly increasing trend with higher MAapp. Significant changes were found for SUVmean and SUVmax between the high versus low MAapp and medium versus low MAapp (both p < 0.05), but not between the high versus medium MAapp (p = 0.055 and 0.25, respectively). The effect of varying MAapp was more pronounced in low expressing tumors and PSMA expressing tissues (e.g. salivary glands and kidneys). Overall, administration of a high MAapp increases the detection of low expression tumors while also increasing uptake in PSMA expressing tissues, possibly leading to false positive findings. In radioligand therapy, a medium MAapp could reduce radiation exposure to dose-limiting organs with only limited effect on radionuclide accumulation in the tumor.

scholarly journals Impact of the Specific Activity and PSMA Expression Level on 18F-AlF-PSMA-11 Uptake in Prostate Cancer

2021 ◽  
Author(s):  
Sarah Piron ◽  
Jeroen Verhoeven ◽  
Emma De Coster ◽  
Benedicte Descamps ◽  
Ken Kersemans ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Activity ◽  
Preclinical Study ◽  
Radioligand Therapy ◽  
Limited Effect ◽  
Reduce Radiation Exposure ◽  
Increasing Trend ◽  
Target Binding ◽  
Specific Membrane ◽  
Psma Expression

Abstract This two-part preclinical study aims to evaluate prostate specific membrane antigen (PSMA) as a valuable target for expression-based imaging applications and to determine changes in target binding in function of varying specific activities (SA) of 18F-AlF-PSMA-11. For the evaluation of PSMA expression levels, male NOD/SCID mice bearing prostate cancer (PCa) xenografts of C4-2 (PSMA+++), 22Rv1 (PSMA+) and PC-3 (PSMA-) were administered 18F-AlF-PSMA-11 with a medium SA (20.26 ± 3.25 MBq/µg). SUVmean and SUVmax values were respectively 3.22 and 3.17 times higher for the high vs low PSMA expressing tumors (p < 0.0001). To evaluate the effect of varying SA, C4-2 and 22Rv1 xenograft bearing mice underwent additional 18F-AlF-PSMA-11 imaging with a high (213.3 ± 39.3 MBq/µg) and/or low SA (1.94 ± 0.27 MBq/µg). SUV values showed a significantly increasing trend with higher SA. Significant changes were found for SUVmean and SUVmax between the high vs low SA and medium vs low SA (both p < 0.05), but not between the high vs medium SA (p = 0.055 and 0.25, respectively). The effect of varying SA was more pronounced in low expressing tumors and PSMA expressing tissues (e.g. salivary glands and kidneys). Overall, administration of a high SA increases the detection of low expression tumors while also increasing uptake in PSMA expressing tissues, possibly leading to false positive findings. In radioligand therapy, a medium SA could reduce radiation exposure to dose-limiting organs with only limited effect on radionuclide accumulation in the tumor.

scholarly journals PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports

2021 ◽  
Author(s):  
M. J. M. Uijen ◽  
Y. H. W. Derks ◽  
R. I. J. Merkx ◽  
M. G. M. Schilham ◽  
J. Roosen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Current Knowledge ◽  
Salivary Gland Cancer ◽  
Clinical Implementation ◽  
Radioligand Therapy ◽  
Psma Pet ◽  
Pet Ct ◽  
Specific Membrane ◽  
Psma Expression

AbstractIn the past decade, a growing body of literature has reported promising results for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and therapy in prostate cancer. First clinical studies evaluating the efficacy of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) demonstrated favorable results in prostate cancer patients. [177Lu]Lu-PSMA is generally well tolerated due to its limited side effects. While PSMA is highly overexpressed in prostate cancer cells, varying degrees of PSMA expression have been reported in other malignancies as well, particularly in the tumor-associated neovasculature. Hence, it is anticipated that PSMA-RLT could be explored for other solid cancers. Here, we describe the current knowledge of PSMA expression in other solid cancers and define a perspective towards broader clinical implementation of PSMA-RLT. This review focuses specifically on salivary gland cancer, glioblastoma, thyroid cancer, renal cell carcinoma, hepatocellular carcinoma, lung cancer, and breast cancer. An overview of the (pre)clinical data on PSMA immunohistochemistry and PSMA PET/CT imaging is provided and summarized. Furthermore, the first clinical reports of non-prostate cancer patients treated with PSMA-RLT are described.

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma

2019 ◽  
Vol 58 (04) ◽  
pp. 328-330 ◽  
Author(s):  
Michael Jüptner ◽  
Marlies Marx ◽  
Maaz Zuhayra ◽  
Ulf Lützen
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Molecular Surface ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Radioligand Therapy ◽  
Castration Resistant ◽  
Tumor Tissues ◽  
Specific Membrane ◽  
Psma Expression

IntroductionSystemic radionuclide therapy with 177Lu-PSMA-617 is a novel treatment option in patients with metastasized and castration-resistant prostate cancer 4. The molecular target of the 177Lu-PSMA-617 radioligand therapy is the prostate-specific membrane antigen (PSMA) highly expressed on prostate cancer cells. Beyond the enhanced accumulation of PSMA on prostate cancer cells, PSMA expression is also found on the molecular surface or in the tumor-associated neovasculature of various tumor tissues including sarcomas of the soft tissue 2. Thus, PSMA has theoretically been discussed as a possible future target for systemic radioligand therapy with 177Lu-PSMA-617 even in non-prostate malignancies 1.Here we report on a female patient with extended metastasized leiomyosarcoma experimentally treated with one application of 177Lu-PSMA-617 radioligand therapy.

479: Prostate-Specific Membrane Antigen (PSMA) Expression as a Predictor of Prostate Cancer Progression

2006 ◽  
Vol 175 (4S) ◽  
pp. 155-156
Author(s):  
Matthias D. Hofer ◽  
Sven Perner ◽  
Haojie Li ◽  
Rainer Kuefer ◽  
Richard E. Hautmann ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Prostate Specific Membrane Antigen ◽  
Prostate Cancer Progression ◽  
Specific Membrane ◽  
Psma Expression

scholarly journals PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under 177Lu-PSMA-617 Radioligand Therapy

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2938
Author(s):  
Liam Widjaja ◽  
Rudolf A. Werner ◽  
Tobias L. Ross ◽  
Frank M. Bengel ◽  
Thorsten Derlin
Keyword(s):  
Prostate Cancer ◽  
Whole Body ◽  
Biochemical Response ◽  
Clinical Parameters ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Castration Resistant ◽  
Psa Response ◽  
High Age ◽  
Psma Expression

177Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after two cycles of RLT. In total, 71 mCRPC patients who had undergone PET/computed tomography (CT) with 68Ga-PSMA-11 prior to two cycles of 177Lu-PSMA-617 RLT were included. Malignant lesions on pretherapeutic PET/CTs were manually segmented and average maximum PSMA expression (maximum standardized uptake values, SUVmax), whole-body PSMA-tumor volume (TV), and whole-body total lesion (TL)-PSMA were calculated. We then tested the predictive performance of these parameters for early biochemical response (defined as prostate-sepcific antigen (PSA) decrease of ≥50% according to PCWG2) after two cycles of RLT, relative to established clinical parameters. Early PSA response was observed in 34/71 patients. PSA change after two cycles of RLT correlated with pretherapeutic SUVmax (r = −0.49; p < 0.001), but not with PSMA-TV (r = 0.02; p = 0.89) or TL-PSMA (r = −0.15; p = 0.22). A cut-off of 19.8 for SUVmax and 75.5 years for age was defined by receiver operating characteristics and revealed a significant outcome difference for early biochemical response between patients with adversely low vs. high PSMA expression and low vs. high age (p < 0.001). Multivariate analysis identified SUVmax (HR, 7.94, p = 0.001) and age (HR, 8.05, p = 0.002) as independent predictors for PSA response early in the treatment course. Thus, high age and high PSMA expression in patients scheduled for RLT identify patients with early biochemical response. This study provides a rationale for further prospective studies exploring PET-guided treatment intensification in selected patients.

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