<sup>18</sup>F-rhPSMA-7 PET for the Detection of Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy

Eiber, Matthias; Kroenke, Markus; Wurzer, Alexander; Ulbrich, Lena; Jooß, Lena; Maurer, Tobias; Horn, Thomas; Schiller, Kilian; Langbein, Thomas; Buschner, Gabriel; Wester, Hans‐Jürgen; Weber, Wolfgang

doi:10.2967/jnumed.119.234914

Cited by 76 publications

(63 citation statements)

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“…The chemical identity of the 18 7) has already been assessed for PET imaging of primary and metastatic castration-resistant prostate cancer. Biodistribution of [ 18 F, nat Ga]rhPSMA-7 was found to be similar to that of established PSMA ligands, and [ 18 F, nat Ga]rhPSMA-7 PET/CT demonstrated high detection rates in early biochemical recurrence after radical prostatectomy, especially among patients with low prostate-specific antigen values [16]. Furthermore, the novel tracer outperformed morphologic imaging for N-staging of high-risk primary prostate cancer, with efficacy comparable to the literature data for [ 68 Ga]Ga-PSMA-11 [17].…”

Section: Introductionmentioning

confidence: 73%

“…The novel radiohybrid PSMA-targeting ligand [ 18 F, nat Ga] rhPSMA-7 already demonstrated promising results in staging and restaging of prostate cancer [16,17]. Since the compound is composed of four stereoisomers ([ 18 F, nat Ga]rhPSMA-7.1, -7.2, -7.3 and -7.4), this study aimed to identify the one isomer with the most promising characteristics for further clinical investigation.…”

Section: Discussionmentioning

confidence: 99%

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Preclinical comparison of four [18F, natGa]rhPSMA-7 isomers: influence of the stereoconfiguration on pharmacokinetics

et al. 2020

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Introduction Radiohybrid (rh) ligands, a novel class of prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals, can be labeled either with [18F]fluorine via isotopic exchange or with radiometals (such as [68Ga]Gallium, [177Lu]Lutetium, [225Ac]Actinium). Among these, [18F, natGa]rhPSMA-7 has recently entered clinical assessment. Aim Since [18F, natGa]rhPSMA-7 is composed of four stereoisomers ([18F, natGa]rhPSMA-7.1, -7.2, -7.3 and -7.4), we initiated a preclinical selection process to identify the isomer with the most favorable pharmacokinetics for further clinical investigation. Methods A synthetic protocol for enantiopure [19F, natGa]rhPSMA-7 isomers has been developed. The comparative evaluation of the four isomers comprised human serum albumin binding, lipophilicity, IC50, internalization and classical biodistribution studies and competition experiments in LNCaP tumor-bearing CB-17 SCID mice. In addition, a radio high-performance liquid chromatography-based method was developed allowing quantitative, intraindividual comparison of [18F, natGa]rhPSMA-7.1 to -7.4 in LNCaP tumor-bearing mice. Results Cell studies revealed high PSMA affinity and internalization for [18/19F, natGa]rhPSMA-7.2, -7.3 and -7.4, whereas [18/19F, natGa]rhPSMA-7.1 showed approximately twofold lower values. Although the biodistribution profile obtained was typical of PSMA inhibitors, it did not allow for selection of a lead candidate for clinical studies. Thus, an intraindividual comparison of all four isomers in LNCaP tumor-bearing mice was carried out by injection of a diastereomeric mixture, followed by analysis of the differential uptake and excretion pattern of each isomer. Based on its high tumor accumulation and low uptake in blood, liver and kidneys, [18F, natGa]rhPSMA-7.3 was identified as the preferred isomer and transferred into clinical studies. Conclusion [18F, natGa]rhPSMA-7.3 has been selected as a lead compound for clinical development of a [18F]rhPSMA-based candidate. The intraindividual differential uptake and excretion analysis in vivo allowed for an accurate comparison and assessment of radiopharmaceuticals.

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Section: Introductionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Preclinical comparison of four [18F, natGa]rhPSMA-7 isomers: influence of the stereoconfiguration on pharmacokinetics

et al. 2020

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“…The novel PSMA ligand 18 F-rhPSMA-7 offers several advantages over more established PSMA-based tracers, such as 68 Ga-PSMA-11, and has already shown encouraging data for detection efficacy in biochemical recurrence (40). The considerably longer half-life of 110 min yields the advantages of easier handling and potential wide-range distribution due to large-scale cyclotron-based production of 18 F. Furthermore, spatial resolution might be improved by a lower positron range (41).…”

Section: Discussionmentioning

confidence: 99%

Histologically Confirmed Diagnostic Efficacy of ¹⁸F-rhPSMA-7 PET for N-Staging of Patients with Primary High-Risk Prostate Cancer

et al. 2019

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18 F-rhPSMA-7 (radiohybrid prostate-specific membrane antigen [PSMA]) is a novel ligand for PET imaging. Here, we present data from a retrospective analysis using PET/CT and PET/MRI examinations to investigate the efficacy of 18 F-rhPSMA-7 PET for primary N-staging of patients with prostate cancer (PC) compared with morphologic imaging (CT or MRI) and validated by histopathology. Methods: Data from 58 patients with high-risk PC (according to the D'Amico criteria) who were staged with 18 F-rhPSMA-7 PET/CT or PET/MRI at our institution between July 2017 and June 2018 were reviewed. The patients had a median prescan prostate-specific antigen value of 12.2 ng/mL (range, 1.2-81.6 ng/mL). The median injected activity of 18 F-rhPSMA-7 was 327 MBq (range, 132-410 MBq), with a median uptake time of 79.5 min (range, 60-153 min). All patients underwent subsequent radical prostatectomy and extended pelvic lymph node dissection. The presence of lymph node metastases was determined by an experienced reader independently for both the PET and the morphologic datasets using a template-based analysis on a 5-point scale. Patient-level and template-based results were both compared with histopathologic findings. Results: Lymph node metastases were present in 18 patients (31.0%) and were located in 52 of 375 templates (13.9%). Receiver-operating-characteristic analyses showed 18 F-rhPSMA-7 PET to perform significantly better than morphologic imaging on both patient-based and template-based analyses (areas under curve, 0.858 vs. 0.649 [P 5 0.012] and 0.765 vs. 0.589 [P , 0.001], respectively). On patient-based analyses, the sensitivity, specificity, and accuracy of 18 F-rhPSMA-7 PET were 72.2%, 92.5%, and 86.2%, respectively, and those of morphologic imaging were 50.0%, 72.5%, and 65.5%, respectively. On template-based analyses, the sensitivity, specificity, and accuracy of 18 F-rhPSMA-7 PET were 53.8%, 96.9%, and 90.9%, respectively, and those of morphologic imaging were 9.6%, 95.0%, and 83.2%, respectively. Conclusion: 18 F-rhPSMA-7 PET is superior to morphologic imaging for N-staging of high-risk primary PC. The efficacy of 18 F-rhPSMA-7 is similar to published data for 68 Ga-PSMA-11.

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“…Initial clinical assessment of [ 18 F]Ga-rhPSMA-7 (often abbreviated as [ 18 F]rhPSMA-7; Fig. 1 ) revealed excellent diagnostic performance for N-staging of high-risk primary prostate cancer and localization of biochemical recurrence after radical prostatectomy, especially in patients with low prostate-specific antigen levels (Kroenke et al, 2020 ; Eiber et al, 2020 ; Oh et al, 2020 ). Since [ 18 F]Ga-rhPSMA-7 is present as a mixture of four stereoisomers ([ 18 F]Ga-rhPSMA-7.1, − 7.2, − 7.3 and − 7.4; see Fig.…”

Section: Introductionmentioning

confidence: 99%

Automated synthesis of [18F]Ga-rhPSMA-7/ -7.3: results, quality control and experience from more than 200 routine productions

Wurzer

Carlo

Herz

et al. 2021

EJNMMI radiopharm. chem.

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Introduction The radiohybrid (rh) prostate-specific membrane antigen (PSMA)-targeted ligand [18F]Ga-rhPSMA-7 has previously been clinically assessed and demonstrated promising results for PET-imaging of prostate cancer. The ligand is present as a mixture of four stereoisomers ([18F]Ga-rhPSMA-7.1, − 7.2, − 7.3 and − 7.4) and after a preclinical isomer selection process, [18F]Ga-rhPSMA-7.3 has entered formal clinical trials. Here we report on the establishment of a fully automated production process for large-scale production of [18F]Ga-rhPSMA-7/ -7.3 under GMP conditions (EudraLex). Methods [18F]Fluoride in highly enriched [18O]H2O was retained on a strong anion exchange cartridge, rinsed with anhydrous acetonitrile and subsequently eluted with a solution of [K+ ⊂ 2.2.2]OH− in anhydrous acetonitrile into a reactor containing Ga-rhPSMA ligand and oxalic acid in DMSO. 18F-for-19F isotopic exchange at the Silicon-Fluoride Acceptor (SiFA) was performed at room temperature, followed by dilution with buffer and cartridge-based purification. Optimum process parameters were determined on the laboratory scale and thereafter implemented into an automated synthesis. Data for radiochemical yield (RCY), purity and quality control were analyzed for 243 clinical productions (160 for [18F]Ga-rhPSMA-7; 83 for [18F]Ga-rhPSMA-7.3). Results The automated production of [18F]Ga-rhPSMA-7 and the single isomer [18F]Ga-rhPSMA-7.3 is completed in approx. 16 min with an average RCY of 49.2 ± 8.6% and an excellent reliability of 98.8%. Based on the different starting activities (range: 31–130 GBq, 89 ± 14 GBq) an average molar activity of 291 ± 62 GBq/μmol (range: 50–450 GBq/μmol) was reached for labeling of 150 nmol (231 μg) precursor. Radiochemical purity, as measured by radio-high performance liquid chromatography and radio-thin layer chromatography, was 99.9 ± 0.2% and 97.8 ± 1.0%, respectively. Conclusion This investigation demonstrates that 18F-for-19F isotopic exchange is well suited for the fast, efficient and reliable automated routine production of 18F-labeled PSMA-targeted ligands. Due to its simplicity, speed and robustness the development of further SiFA-based radiopharmaceuticals is highly promising and can be of far-reaching importance for future theranostic concepts.

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¹⁸F-rhPSMA-7 PET for the Detection of Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy

Cited by 76 publications

References 41 publications

Preclinical comparison of four [18F, natGa]rhPSMA-7 isomers: influence of the stereoconfiguration on pharmacokinetics

Preclinical comparison of four [18F, natGa]rhPSMA-7 isomers: influence of the stereoconfiguration on pharmacokinetics

Histologically Confirmed Diagnostic Efficacy of ¹⁸F-rhPSMA-7 PET for N-Staging of Patients with Primary High-Risk Prostate Cancer

Automated synthesis of [18F]Ga-rhPSMA-7/ -7.3: results, quality control and experience from more than 200 routine productions

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18F-rhPSMA-7 PET for the Detection of Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy

Cited by 76 publications

References 41 publications

Preclinical comparison of four [18F, natGa]rhPSMA-7 isomers: influence of the stereoconfiguration on pharmacokinetics

Preclinical comparison of four [18F, natGa]rhPSMA-7 isomers: influence of the stereoconfiguration on pharmacokinetics

Histologically Confirmed Diagnostic Efficacy of 18F-rhPSMA-7 PET for N-Staging of Patients with Primary High-Risk Prostate Cancer

Automated synthesis of [18F]Ga-rhPSMA-7/ -7.3: results, quality control and experience from more than 200 routine productions

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Product

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¹⁸F-rhPSMA-7 PET for the Detection of Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy

Histologically Confirmed Diagnostic Efficacy of ¹⁸F-rhPSMA-7 PET for N-Staging of Patients with Primary High-Risk Prostate Cancer