The Effect of Total Tumor Volume on the Biologically Effective Dose to Tumor and Kidneys for ¹⁷⁷Lu-Labeled PSMA Peptides

Abstract

The aim of this work was to simulate the effect of prostate-specific membrane antigen (PSMA)-positive total tumor volume (TTV) on the biologically effective doses (BEDs) to tumors and organs at risk in patients with metastatic castration-resistant prostate cancer who are undergoing Lu-PSMA radioligand therapy. A physiologically based pharmacokinetic model was fitted to the data of 13 patients treated with Lu-PSMA I&T (a PSMA inhibitor for imaging and therapy). The tumor, kidney, and salivary gland BEDs were simulated for TTVs of 0.1-10 L. The activity and peptide amounts leading to an optimal tumor-to-kidneys BED ratio were also investigated. When the TTV was increased from 0.3 to 3 L, the simulated BEDs to tumors, kidneys, parotid glands, and submandibular glands decreased from 22 ± 15 to 11.0 ± 6.0 Gy, 6.5 ± 2.3 to 3.7 ± 1.4 Gy, 11.0 ± 2.7 to 6.4 ± 1.9 Gy, and 10.9 ± 2.7 to 6.3 ± 1.9 Gy, respectively (where the subscripts denote that an α/β of 1.49, 2.5, or 4.5 Gy was used to calculate the BED). The BED to the red marrow increased from 0.17 ± 0.05 to 0.32 ± 0.11 Gy For patients with a TTV of more than 0.3 L, the optimal amount of peptide was 273 ± 136 nmol and the optimal activity was 10.4 ± 4.4 GBq. This simulation study suggests that in patients with large PSMA-positive tumor volumes, higher activities and peptide amounts can be safely administered to maximize tumor BEDs without exceeding the tolerable BED to the organs at risk.

Treatment planning algorithm for peptide receptor radionuclide therapy considering multiple tumor lesions and organs at risk

“…The presented treatment‐planning workflow can also be used for other therapies using radiolabeled ligands (eg, radioimmunotherapy and PSMA‐radioligand therapy) . Moreover, because of its PBPK‐model basis, the described algorithm can additionally include the optimization of the administration schedule which may also consider modulation of the biokinetics using biokinetics‐favoring substances (eg, preload) …”

Technical Note: Optimal sampling schedules for kidney dosimetry based on the hybrid planar/SPECT method in 177Lu‐PSMA therapy

“…The used patient cohort is described in detail elsewhere . In brief, 13 patients [age: (70 ± 6) yr] with mCRPC [median (range) total tumor volume: 236 ml (12, 5800 ml)] underwent 177 Lu‐PSMA I&T therapy [activity: (7.3 ± 0.3) GBq, peptide amount: (91 ± 5) nmol].…”

“…Virtual patients (P 1 –P 13 ) were created by fitting a whole‐body physiologically based pharmacokinetic (PBPK) model to the biokinetic data. The PBPK model is described elsewhere . The virtual patients were then used to simulate TACs of the kidneys (Fig.…”

“…The used patient cohort is described in detail elsewhere. 1,16,17 In brief, 13 patients [age: (70 AE 6) yr] with mCRPC [median (range) total tumor volume: 236 ml (12, 5800 ml)] underwent 177 Lu-PSMA I&T therapy [activity: (7.3 AE 0.3) GBq, peptide amount: (91 AE 5) nmol]. The individual biokinetics were measured with planar whole-body scans at 30-120 min, 24 h, and 7 days post injection (p.i.).…”

“…The PBPK model is described elsewhere. [16][17][18] The virtual patients were then used to simulate TACs of the kidneys (Fig. 1), which were used as ground truth.…”