Analysis of [18F]rhPSMA-7.3

[18F]rhPSMA-7.3 can be used for imaging PSMA expressing tumours, mainly primary and metastatic prostate cancer, but also non-prostate cancers due to PSMA expression in the neovasculature. As a radiohybrid (therefore the "rh" in the name; not to be confused with recombinant human PSMA) it can be labelled with several radiometals in its DOTAGA moiety. Thus [18F]rhPSMA-7.3 PET could be used to select the patients that would benefit of radiotherapy with β- or α-emitting radiometals, such as 177Lu, or, [18F][177Lu]rhPSMA-7.3 could be used to simultaneously perform the radiotherapy and assess its distribution kinetics with PET. In contrast to the more traditional radioimmunotherapy, the kinetics are fast due to the small size of rhPSMA-7.3. Like other small-molecule PSMA ligands, rhPSMA-7.3 binds to the extracellular domain of PSMA, and can then be internalized.

rhPSMA-7 has four isomers, from which rhPSMA-7.3 has the best characteristics for clinical use. [18F]rhPSMA-7 and rhPSMA-7.3 has been shown to offer good sensitivity, specificity, and accuracy for N-staging of high-risk primary prostate cancer (Kroenke et al., 2020; Langbein et al., 2022), and to detect metastases in men after radical prostatectomy at least as well as [68Ga]PSMA-11 and other PSMA radioligands (Eiber et al., 2019a, 2019b, and 2020; Krönke et al., 2019; Maurer et al., 2019; Ilhan et al., 2019; Jooss et al., 2019; Ulbrich et al., 2019). Positive predictive value is high in biochemical recurrence of prostate cancer after radical prostatectomy, and correct detection rate is excellent in patients with prescan PSA ≥1 ng/mL (Chantadisai et al., 2021). [18F]rhPSMA-7.3 PET offers high detection efficacy and predictive value in patients with biochemical recurrence of prostate cancer after radical prostatectomy and before potential salvage therapy (Rauscher et al., 2021; Kroenke et al., 2022). Both primary and metastatic prostate cancer lesions can be detected (Malaspina et al., 2022).

Radiation dosimetry is favourable for [18F]rhPSMA-7.3 and [18F]rhPSMA-7 (Oh et al., 2019a; Tolvanen et al., 2021). Biodistribution of [18F]rhPSMA-7 and [18F]rhPSMA-7.3 is broadly similar (Knorr et al., 2022).

Uptake of the racemic mixture [18F]rhPSMA-7 is high in the salivary glands, kidneys, and urinary bladder, and moderate in the liver, spleen, and duodenum, and low in the blood, lungs, and normal bone (Oh et al., 2020). Renal uptake and urine activity in the bladder is lower with [18F]rhPSMA-7.3 than with [18F]rhPSMA-7 (Oh et al., 2019a), and, when diuretic is used, retention of [18F]rhPSMA-7 in the bladder was clearly lower than that of [68Ga]PSMA-11 (Oh et al., 2020). SUVmean in prostate cancer lesions was in average ∼30, which was ∼15 times higher than in the blood (Oh et al., 2019a). With [18F]rhPSMA-7, SUV60-88min was 10.1±7 for prostate lesions, 13±4.8 for lymph node metastases, and 5.7±3.1 for bone metastases (Malaspina et al., 2021). The [18F]rhPSMA-7 SUV decreases with time in blood and lungs, and increases in the kidneys, bladder, and bones and bone marrow; kidney uptake is highly variable (Oh et al., 2020). Increasing injected activity increases background activity but not SUV in lesions, and thus reduced overall image quality, possibly because administered dose was set based on body weight. The overall image quality, for [18F]rhPSMA-7, was stable up to 2.5 h, and therefore imaging 50-70 min p.i. is recommended (Oh et al., 2019b; 2020). Also with [18F]rhPSMA-7, the optimal visual lesion detection starts from 60 min post-injection (Malaspina et al., 2021). When muscle (gluteus maximus) was used as reference region, the SUV ratio was seen to increase from ∼10 at 1 h p.i. to ∼30 at 3h p.i.; the SUV in lesions was seen to increase until 60 min, and the increase in the SUV ratio after this was due to decreased SUV in the reference tissue (Hohberg et al., 2018). Other PSMA radioligands have also shown increased tumour-to-background ratio at late scans (Sahlmann et al., 2016; Schmuck et al., 2017; Rahbar et al., 2018; Hohberg et al., 2019a and 2019b; Alberts et al., 2020), and in preclinical ex vivo studies (Chen et al., 2008).

Analysis of dynamic [18F]rhPSMA-7 PET imaging data shows that uptake in lesions is almost irreversible at least 2 hours post injection. Patlak plot results are in good agreement with SUV and lesion-to-background ratios, suggesting that static late scan 60 min post-injection or later, without blood sampling, can be used for diagnostic imaging (Malaspina et al., 2021).

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Eiber M, Kroenke M, Wurzer A, Ulbrich L, Jooss L, Maurer T, Horn T, Schiller K, Langbein T, Buschner G, Wester H-J, Weber W. 18F-rhPSMA-7 positron emission tomography for the detection of biochemical recurrence of prostate cancer following radical prostatectomy. J Nucl Med. 2020; 61(5): 696-701. doi: 10.2967/jnumed.119.234914.

Kroenke M, Wurzer A, Schwamborn K, Ulbrich L, Jooss L, Maurer T, Horn T, Rauscher I, Haller B, Herz M, Wester H-J, Weber WA, Eiber M. Histologically-confirmed diagnostic efficacy of 18F-rhPSMA-7 positron emission tomography for N-staging of patients with primary high risk prostate cancer. J Nucl Med. 2020; 61(5): 710-715. doi: 10.2967/jnumed.119.234906.

Malaspina S, Oikonen V, Kuisma A, Ettala O, Mattila K, Boström PJ, Minn H, Kalliokoski K, Postema EJ, Miller MP, Scheinin M. Kinetic analysis and optimisation of 18F-rhPSMA-7.3 PET imaging of prostate cancer. Eur J Nucl Med Mol Imaging 2021; 48: 3723-3731. doi: 10.1007/s00259-021-05346-8.

Notohamiprodjo S, Eiber M, Lohrmann C, Weber WA. Temporary reactive response of axillary lymph nodes to COVID-19 vaccination on 18F-rhPSMA-7.3 PET/CT in patients with prostate cancer. J Nucl Med. 2022; 63: 1673-1676. doi: 10.2967/jnumed.121.263758.

Oh SW, Worzer A, Teoh EJ, Oh S, Langbein T, Krönke M, Herz M, Kropf S, Wester H-J, Weber WA, Eiber M. Quantitative and qualitative analyses of biodistribution and PET image quality of novel radiohybrid PSMA, 18F-rhPSMA-7, in patients with prostate cancer. J Nucl Med. 2020; 61(5): 702-709. doi: 10.2967/jnumed.119.234609.

Tolvanen T, Kalliokoski K, Malaspina S, Kuisma A, Lahdenpohja S, Postema EJ, Miller MP, Scheinin M. Safety, biodistribution, and radiation dosimetry of 18F-rhPSMA-7.3 in healthy adult volunteers. J Nucl Med. 2021; 62(5): 679-684. doi: 10.2967/jnumed.120.252114.

Wurzer A, Di Carslo D, Schmidt A, Beck R, Eiber M, Schwaiger M, Wester H-J. Radiohybrid ligands: a novel tracer concept exemplified by 18F- or 68Ga-labeled rhPSMA-inhibitors. J Nucl Med. 2020; 61(5): 735-742. doi: 10.2967/jnumed.119.234922.

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Updated at: 2023-01-22
Created at: 2019-12-03
Written by: Vesa Oikonen