Abstract
Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy has become an established treatment option for metastatic castration-resistant prostate cancer. Although lutetium-177 (177Lu) PSMA therapy has shown promising clinical benefits, terbium-161 (161Tb) PSMA is an emerging theranostic agent offering potential advantages due to its combination of beta and Auger electron emissions. This work presents the first documented case in Thailand and Southeast Asia of a patient treated at Ramathibodi Hospital with 161Tb-PSMA following progression on 177Lu-PSMA therapy. This report describes the clinical application of this novel radiopharmaceutical, the implementation of quantitative imaging protocols, single photon emission computed tomography/computed tomography calibration processes, and absorbed dose estimations from voxel-based dosimetry that contributed to individualised treatment planning.
Introduction
Metastatic castration-resistant prostate cancer (mCRPC) remains a major clinical challenge, characterised by progression despite androgen deprivation therapy (ADT) and the use of second-line systemic treatments (1,2). Theranostic approaches targeting the prostate-specific membrane antigen (PSMA) with radiolabelled compounds, such as lutetium-177 (177Lu)-PSMA, have demonstrated significant therapeutic benefits. However, a subset of patients ultimately develops resistance or progresses despite multiple cycles of 177Lu-PSMA therapy (3).
Terbium-161 (161Tb)-PSMA is a novel radionuclide offering theoretical advantages over 177Lu-PSMA, including higher linear energy transfer and the emission of conversion and Auger electrons, which may enhance therapeutic efficacy, particularly in small-volume or micro-metastatic disease. However, clinical data on 161Tb-PSMA therapy remain extremely limited, especially in Southeast Asia (1,4,5).
This report presents the first clinical application of 161Tb-PSMA therapy in Thailand and Southeast Asia, providing early insights into integrating quantitative single photon emission computed tomography (SPECT) imaging and the voxel-based absorbed dose estimation in the therapeutic process.
Discussion
Post-therapeutic quantitative SPECT/CT imaging following 161Tb-PSMA therapy (6283 MBq or 169.81 mCi) enabled voxel-based dosimetry using AI-assisted segmentation (Figure 1). The absorbed dose distribution effectively targeted PSMA-avid lesions while maintaining acceptable radiation exposure to normal organs. This favourable tumor-to-organ dose distribution is consistent with recently reported multicentre clinical experience with 161Tb-PSMA, which demonstrated safe organ dosimetry and promising antitumor activity even in patients refractory to prior 177Lu-PSMA therapy (7).
The mean absorbed dose to the kidneys was 1.83 Gy, with 1.97 Gy delivered to the left kidney and 1.69 Gy to the right kidney, both remaining well below established renal tolerance thresholds. Other organs received relatively low absorbed doses, including 0.48 Gy to the liver and 0.63 Gy to the spleen. Lung doses were asymmetrical, with 3.61 Gy to the left lung corresponding to metastatic involvement and 0.49 Gy to the right lung. Skeletal lesions exhibited the highest absorbed doses, with the lesion in the left femur receiving 6.51 Gy and the lumbar spine lesion 5.23 Gy, as summarised in Figure 2, which includes the AI-assisted organ segmentation. Comparable organ absorbed doses and higher lesion doses have been reported in multicentre studies, supporting the therapeutic selectivity of 161Tb-PSMA while maintaining organ safety margins (7).
An intra-patient comparison of renal dosimetry was undertaken between the 12th treatment cycle with 177Lu-PSMA in March 2024 and the 14th cycle with 161Tb-PSMA in February 2025, as illustrated in Table 1. For the 177Lu-PSMA cycle, dosimetry was performed using a single time-point (STP) based on the Hänscheid approach, with quantitative SPECT/CT imaging obtained approximately 48 hours post-administration. The mean kidney absorbed dose was 1.84 Gy, corresponding to a dose-per-activity ratio of 0.22 mGy/MBq. In contrast, the 161Tb-PSMA therapy incorporated a multiple time-point imaging protocol, as STP models for 161Tb-PSMA are not yet established. Despite methodological differences, the mean kidney absorbed dose during the 161Tb-PSMA cycle remained comparable at 1.83 Gy. However, the mean absorbed dose per administered activity was slightly higher at 0.29 mGy/MBq.
This observation aligns with published dosimetric data showing that 161Tb-PSMA may deliver similar macroscopic organ doses to 177Lu-PSMA while potentially providing enhanced microscopic dose deposition due to the emission of short-range Auger electrons (7). The modest increase in dose-per-activity in the present case may also reflect differences in disease burden and radiopharmaceutical kinetics, as the patient demonstrated more advanced disease progression at the time of 161Tb-PSMA therapy. Previous studies suggest that 161Tb-PSMA may be particularly effective in heterogeneous or micrometastatic disease, although current macrodosimetry approaches may underestimate its true biologic impact (7). Given the evolving metastatic landscape between treatment cycles, lesion-specific absorbed doses were not directly compared.
From a clinical perspective, biochemical response after 161Tb-PSMA therapy was limited. Serum PSA increased from 918 ng/mL prior to treatment to 978 ng/mL at early post-therapy assessment, consistent with advanced disease burden and possible delayed or absent biochemical response in this heavily pretreated setting. In contrast, a marked symptomatic improvement was observed. The patient’s pain, previously rated as 5 out of 10 at the right thigh, improved substantially after 161Tb-PSMA therapy, with a post-treatment pain score of 0-1 out of 10, allowing discontinuation of tramadol and NSAID analgesics.
Regarding treatment-related toxicity, 161Tb-PSMA was generally well tolerated. The patient experienced transient fatigue and malaise during the first week after therapy, which resolved spontaneously. Xerostomia was not newly observed and was attributed to cumulative prior 177Lu-PSMA treatments, for which the patient continued to use artificial saliva.
Laboratory monitoring demonstrated stable renal function and hematologic parameters following 161Tb-PSMA administration. Serum creatinine showed a mild increase from 1.25 mg/dL before therapy to 1.31 mg/dL after therapy, without clinical evidence of nephrotoxicity. Hematologic indices remained stable, with haematocrit changing from 29.0% to 28.9% and platelet count decreasing from 185000/µL to 159000/µL, without clinically significant cytopenia. These findings are consistent with previously reported safety profiles of 161Tb-PSMA therapy (7).
Discussion
Post-therapeutic quantitative SPECT/CT imaging following 161Tb-PSMA therapy (6283 MBq or 169.81 mCi) enabled voxel-based dosimetry using AI-assisted segmentation (Figure 1). The absorbed dose distribution effectively targeted PSMA-avid lesions while maintaining acceptable radiation exposure to normal organs. This favourable tumor-to-organ dose distribution is consistent with recently reported multicentre clinical experience with 161Tb-PSMA, which demonstrated safe organ dosimetry and promising antitumor activity even in patients refractory to prior 177Lu-PSMA therapy (7).
The mean absorbed dose to the kidneys was 1.83 Gy, with 1.97 Gy delivered to the left kidney and 1.69 Gy to the right kidney, both remaining well below established renal tolerance thresholds. Other organs received relatively low absorbed doses, including 0.48 Gy to the liver and 0.63 Gy to the spleen. Lung doses were asymmetrical, with 3.61 Gy to the left lung corresponding to metastatic involvement and 0.49 Gy to the right lung. Skeletal lesions exhibited the highest absorbed doses, with the lesion in the left femur receiving 6.51 Gy and the lumbar spine lesion 5.23 Gy, as summarised in Figure 2, which includes the AI-assisted organ segmentation. Comparable organ absorbed doses and higher lesion doses have been reported in multicentre studies, supporting the therapeutic selectivity of 161Tb-PSMA while maintaining organ safety margins (7).
An intra-patient comparison of renal dosimetry was undertaken between the 12th treatment cycle with 177Lu-PSMA in March 2024 and the 14th cycle with 161Tb-PSMA in February 2025, as illustrated in Table 1. For the 177Lu-PSMA cycle, dosimetry was performed using a single time-point (STP) based on the Hänscheid approach, with quantitative SPECT/CT imaging obtained approximately 48 hours post-administration. The mean kidney absorbed dose was 1.84 Gy, corresponding to a dose-per-activity ratio of 0.22 mGy/MBq. In contrast, the 161Tb-PSMA therapy incorporated a multiple time-point imaging protocol, as STP models for 161Tb-PSMA are not yet established. Despite methodological differences, the mean kidney absorbed dose during the 161Tb-PSMA cycle remained comparable at 1.83 Gy. However, the mean absorbed dose per administered activity was slightly higher at 0.29 mGy/MBq.
This observation aligns with published dosimetric data showing that 161Tb-PSMA may deliver similar macroscopic organ doses to 177Lu-PSMA while potentially providing enhanced microscopic dose deposition due to the emission of short-range Auger electrons (7). The modest increase in dose-per-activity in the present case may also reflect differences in disease burden and radiopharmaceutical kinetics, as the patient demonstrated more advanced disease progression at the time of 161Tb-PSMA therapy. Previous studies suggest that 161Tb-PSMA may be particularly effective in heterogeneous or micrometastatic disease, although current macrodosimetry approaches may underestimate its true biologic impact (7). Given the evolving metastatic landscape between treatment cycles, lesion-specific absorbed doses were not directly compared.
From a clinical perspective, biochemical response after 161Tb-PSMA therapy was limited. Serum PSA increased from 918 ng/mL prior to treatment to 978 ng/mL at early post-therapy assessment, consistent with advanced disease burden and possible delayed or absent biochemical response in this heavily pretreated setting. In contrast, a marked symptomatic improvement was observed. The patient’s pain, previously rated as 5 out of 10 at the right thigh, improved substantially after 161Tb-PSMA therapy, with a post-treatment pain score of 0-1 out of 10, allowing discontinuation of tramadol and NSAID analgesics.
Regarding treatment-related toxicity, 161Tb-PSMA was generally well tolerated. The patient experienced transient fatigue and malaise during the first week after therapy, which resolved spontaneously. Xerostomia was not newly observed and was attributed to cumulative prior 177Lu-PSMA treatments, for which the patient continued to use artificial saliva.
Laboratory monitoring demonstrated stable renal function and hematologic parameters following 161Tb-PSMA administration. Serum creatinine showed a mild increase from 1.25 mg/dL before therapy to 1.31 mg/dL after therapy, without clinical evidence of nephrotoxicity. Hematologic indices remained stable, with haematocrit changing from 29.0% to 28.9% and platelet count decreasing from 185000/µL to 159000/µL, without clinically significant cytopenia. These findings are consistent with previously reported safety profiles of 161Tb-PSMA therapy (7).
Conclusion
This case represents the first reported clinical application of 161Tb-PSMA therapy in Thailand and Southeast Asia. Quantitative SPECT/CT-based voxel dosimetry demonstrated effective lesion targeting and favourable absorbed dose distribution, with acceptable radiation exposure to normal organs. A comparative intra-patient analysis revealed that the renal absorbed dose per administered activity was slightly higher for 161Tb-PSMA than for 177Lu-PSMA, likely reflecting differences in diseases burden and biodistribution. Although an early biochemical response was not observed, 161Tb-PSMA therapy resulted in marked symptomatic improvement with substantial pain relief and reduced analgesic requirements, while maintaining a favourable safety profile without clinically significant renal or hematologic toxicity. These findings support the role of quantitative imaging, dosimetry and suggest that 161Tb-PSMA may offer a safe and clinically meaningful palliative option in heavily pretreated patients with mCRPC after 177Lu-PSMA therapy.
