Dosimetry of 177Lu-PSMA-617 after Mannitol Infusion and Glutamate Tablet Administration: Preliminary Results of EUDRACT/RSO 2016-002732-32 IRST Protocol

Abstract

Radio-ligand therapy (RLT) with177Lu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate-cancer (mCRPC). A prospective phase-II study (EUDRACT/RSO,2016-002732-32) on mCRPC is ongoing at IRST (Meldola, Italy). A total of 9 patients (median age: 68 y, range: 53–85) were enrolled for dosimetry evaluation of parotid glands (PGs), kidneys, red marrow (RM) and whole body (WB). Folic polyglutamate tablets were orally administered as PGs protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake. The whole body planar image (WBI) and blood samples were acquired at different times post infusion (1 h, 16–24 h, 36–48 h and 120 h). Dose calculation was performed with MIRD formalism (OLINDA/EXM software). The median effective half-life was 33.0 h (range: 25.6–60.7) for PGs, 31.4 h (12.2–80.6) for kidneys, 8.2 h (2.5–14.7) for RM and 40.1 h (31.6–79.7) for WB. The median doses were 0.48 mGy/MBq (range: 0.33–2.63) for PGs, 0.70 mGy/MBq (0.26–1.07) for kidneys, 0.044 mGy/MBq (0.023–0.067) for RM and 0.04 mGy/MBq (0.02–0.11) for WB. A comparison with previously published dosimetric data was performed and a significant difference was found for PGs while no significant difference was observed for the kidneys. For PGs, the possibility of reducing uptake by administering glutamate tablets during RLT seems feasible while further research is warranted for a more focused evaluation of the reduction in kidney uptake.

Targeted Alpha Therapy in mCRPC (Metastatic Castration-Resistant Prostate Cancer) Patients: Predictive Dosimetry and Toxicity Modeling of 225Ac-PSMA (Prostate-Specific Membrane Antigen)

“…Polyglutamate tablets were orally administered as a substrate for PSMA receptors, and external ice packs were applied to the neck region (3). The dosimetry evaluation performed on 13 patients showed a lower absorbed dose in both parotid and submandibular glands compared with previously published data (11,12). The efficacy results of the protectors proposed in our study, especially for salivary glands, were encouraging in the context of TAT, as they could potentially improve treatment management, enabling wider use of this therapeutic approach.…”

“…The salivary gland dose value was calculated as the mean between PG and SG dose values for each patient. More details are reported in Sarnelli et al (11). Although the focus of the present study is salivary glands, for the sake of completeness, we reported the predicted dose also for the other considered organs.…”

“…Organ-specific drug protectors were administered to reduce organ-at-risk uptake (10)(11)(12). For the salivary glands, 30 min before, during, and 4 h after 177 Lu-PSMA infusion, ice packs were applied to the neck region (3,13), and patients were given polyglutamate folate tablets of plant origin (Morgan Pharma Monteviale, Italy).…”

“…Given that Kratochwil et al (8) did not perform any attenuation correction to their patents' data, no attenuation correction was applied in this study. Details on the dosimetry protocol were published in previous works (11,12). Structures of interest for dosimetry evaluation were kidneys, liver, parotid glands (PGs), submandibular glands (SGs), red marrow (RM), and whole body (WB).…”

The Effects of Monosodium Glutamate on PSMA Radiotracer Uptake in Men with Recurrent Prostate Cancer: A Prospective, Randomized, Double-Blind, Placebo-Controlled Intraindividual Imaging Study

“…Furthermore, the increased risk of chronic renal disease prevents initiation of PSMA-RLT earlier in disease course (14). Many attempts including sialendoscopy with dilatation, saline irrigation, steroid injection, intraparenchymal injections of botulinum toxin, external cooling of the salivary glands with ice-packs and oral administration of folic polyglutamate tablets have been tried to mitigate salivary gland toxicity with some, but limited success (15)(16)(17)(18). Mannitol infusion is a strategy to reduce renal uptake of PSMA-targeted tracers by acting as an osmotic diuretic, decreasing renal reabsorption.…”