External radiation exposure, excretion, and effective half-life in 177Lu-PSMA-targeted therapies

Abstract

BackgroundProstate-specific membrane antigen (PSMA)-targeted therapy with 177Lu-PSMA-617 is a therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC). To optimize the therapy procedure, it is necessary to determine relevant parameters to define radiation protection and safety necessities. Therefore, this study aimed at estimating the ambient radiation exposure received by the patient. Moreover, the excreted activity was quantified.ResultsIn total, 50 patients with mCRPC and treated with 177Lu-PSMA-617 (mean administered activity 6.3 ± 0.5 GBq) were retrospectively included in a bi-centric study. Whole-body dose rates were measured at a distance of 2 m at various time points after application of 177Lu-PSMA-617, and effective half-lives for different time points were calculated and compared. Radiation exposure to the public was approximated using the dose integral. For the estimation of the excreted activity, whole body measurements of 25 patients were performed at 7 time points.Unbound 177Lu-PSMA-617 was rapidly cleared from the body. After 4 h, approximately 50% and, after 12 h, approximately 70% of the administered activity were excreted, primarily via urine. The mean dose rates were the following: 3.6 ± 0.7 μSv/h at 2 h p. i., 1.6 ± 0.6 μSv/h at 24 h, 1.1 ± 0.5 μSv/h at 48 h, and 0.7 ± 0.4 μSv/h at 72 h. The mean effective half-life of the cohort was 40.5 ± 9.6 h (min 21.7 h; max 85.7 h). The maximum dose to individual members of the public per treatment cycle was ~ 250 ± 55 μSv when the patient was discharged from the clinic after 48 h and ~ 190 ± 36 μSv when the patient was discharged after 72 h.ConclusionsIn terms of the radiation exposure to the public, 177Lu-PSMA is a safe option of radionuclide therapy. As usually four (sometimes more) cycles of the therapy are performed, it must be conducted in a way that ensures that applicable legal requirements can be followed. In other words, the radiation exposure to the public and the concentration of activity in wastewater must be sub-marginal. Therefore, in certain countries, hospitalization of these patients is mandatory.

Albumin-Binding PSMA Ligands: Implications for Expanding the Therapeutic Window

“…Several factors limit the effectiveness of b-particle radiotherapy, including the modest linear energy transfer of b-particles (6) and poor pharmacokinetics, particularly insufficient dose delivery to the tumor. This limitation is reflected by the recent report that 50% of injected activity of 177 Lu-PSMA-617 is excreted within 4 h of administration and that by 12 h, nearly 70% of the activity has been excreted (7). It has been reported that there is a significantly positive, even logarithmic, relationship between response rate and dose delivered to the tumor in patients treated with 177 Lu-DOTATATE (8), and the high dose delivered to prostate cancer metastases is credited for the reported response of these lesions after radioligand therapy with 177 Lu-PSMA-I&T (4).…”

177Lu-PSMA for advanced prostate cancer: are we ready to play big?

“…To illustrate, the delivery of 177 Lu-PSMA is resource intensive: it requires a radiolabeled intravenous preparation and careful handling and specialist staff together with quality control and post-administration observation [4]. Although in some countries, outpatient administration of radionuclide therapy is allowed, most countries, certainly within Europe, legally prescribe hospitalization for administration [24]. Such hospitalization requires dedicated radiation protection facilities, in which patient rooms are required to have dedicated sanitary facilities and shielded walls [13].…”

“…It is critical that hospitals consciously pay attention to the ecological responsibility and safety of 177 Lu-PSMA [24]. The processing of hazardous medical disposal and the emission of metabolized substance activity, including appropriate storage space, requires radiation protection regarding public and environmental exposure [26].…”

Radionuclide therapy services in an era of COVID-19: the radiation protection challenges, opportunities and considerations

“…The magnitude of the radiation exposure and resultant radiation risk in all these scenarios will be higher from day-case patients compared to that from in-patients due to the higher external dose rates associated with patient contact earlier after administration [ 2 , 3 ]. Additionally, minimising transfer of radioactive contamination from urine, faeces, sweat or saliva in the home will be more challenging to achieve as the earlier discharge also results in higher levels of excretion occurring in the home [ 4 ].…”