Dosimetric Analysis of the Short-Ranged Particle Emitter 161Tb for Radionuclide Therapy of Metastatic Prostate Cancer

Abstract

The aim of this study was to analyze the required absorbed doses to detectable metastases (D_req) when using radionuclides with prostate specific membrane antigen (PSMA)-targeting radioligands to achieve a high probability for metastatic control. The Monte Carlo based analysis was performed for the clinically-used radionuclides yttrium-90, iodine-131, lutetium-177, and actinium-225, and the newly-proposed low-energy electron emitter terbium-161. It was demonstrated that metastatic formation rate highly influenced the metastatic distribution. Lower values generated few large detectable metastases, as in the case with oligo metastases, while high values generated a distribution of multiple small detectable metastases, as observed in patients with diffused visualized metastases. With equal number of detectable metastases, the total metastatic volume burden was 4-6 times higher in the oligo metastatic scenario compared to the diffusely visualized scenario. The D_req was around 30% higher for the situations with 20 detectable metastases compared to one detectable metastasis. The D_req for iodine-131 and yttrium-90 was high (920-3300 Gy). The D_req for lutetium-177 was between 560 and 780 Gy and considerably lower D_req were obtained for actinium-225 and terbium-161, with 240-330 Gy and 210-280 Gy, respectively. In conclusion, the simulations demonstrated that terbium-161 has the potential for being a more effective targeted radionuclide therapy for metastases using PSMA ligands.

Keywords: 161Tb; PSMA; dosimetry; prostate cancer.

Figure 1

Schematic description of the metastatic dissemination model of prostate cancer. The metastatic formation rate (c_p) depends on the volume of the primary tumor (V_p(t)). From the settled metastases (V_mi,i(t)), new metastases can be formed at a metastatic formation rate c_mi. The blue arrows illustrate the dissemination of metastases from the primary tumor, while the green arrows illustrate dissemination from the metastases. The orange doubled arrow illustrates that tumor cells can be disseminated in any direction into already-established metastases [17].

Figure 2

The metastatic distribution for different metastatic formation rates (A) c = 0.16% d⁻¹g⁻¹ (B) c = 2.56% day⁻¹g⁻¹. The dashed blue line indicates the assumed detection limit of metastases, equal to 7 mm. The blue, red, yellow and magenta lines show the metastatic distribution for 1, 5, 10, and 20 detectable metastases (n_d), respectively.

Figure 3

Bone scans performed with [^99mTc]Tc-phosphonate in prostate cancer patients. (A) Initial patient scan visualizing well-defined oligo metastases. (B,C) At later time points, 400 days after initial scanning (B) and 800 days after initial scanning (C), the number of well-defined metastases increased despite continued systemic treatment; (D) A typical patient with diffused visualized metastases in the skeleton.

Figure 4

(A) The absorbed energy fractions for the emitted charged particles and the tumor cure probability (TCP) for ytterium-90 (cyan), iodine-131 (green), lutetium-177 (blue), terbium-161 (black), and actinium-225 (red) in spherical tumor volumes with homogenous activity distribution. (B) Graph shows the TCP curve for the activity concentration that generates an optimal TCP = 0.99, and a TNC = 10, for the sphere masses of 10⁻⁹ (one cell) to 100 g.