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. 2022 Jan;49(2):460-469.
doi: 10.1007/s00259-021-05471-4. Epub 2021 Jul 4.

Intra-therapeutic dosimetry of [177Lu]Lu-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer patients and correlation with treatment outcome

Steffie M B Peters  1 , Bastiaan M Privé  2 , Maarten de Bakker  2 , Frank de Lange  2 , Walter Jentzen  3 , Annemarie Eek  2 , Constantijn H J Muselaers  4 , Niven Mehra  5 , J Alfred Witjes  4 , Martin Gotthardt  2 , James Nagarajah  2 , Mark W Konijnenberg  2   6
Affiliations

Intra-therapeutic dosimetry of [177Lu]Lu-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer patients and correlation with treatment outcome

Steffie M B Peters et al. Eur J Nucl Med Mol Imaging. 2022 Jan.

Abstract

Introduction: While [177Lu]Lu-PSMA radioligand therapy is currently only applied in end-stage metastatic castrate-resistant prostate cancer (mCRPC) patients, also low-volume hormone-sensitive metastatic prostate cancer (mHSPC) patients can benefit from it. However, there are toxicity concerns related to the sink effect in low-volume disease. This prospective study aims to determine the kinetics of [177Lu]Lu-PSMA in mHSPC patients, analyzing the doses to organs at risk (salivary glands, kidneys, liver, and bone marrow) and tumor lesions < 1 cm diameter.

Methods: Ten mHSPC patients underwent two cycles of [177Lu]Lu-PSMA therapy. Three-bed position SPECT/CT was performed at 5 time points after each therapy. Organ dosimetry and lesion dosimetry were performed using commercial software and a manual approach, respectively. Correlation between absorbed index lesion dose and treatment response (PSA drop of > 50% at the end of the study) was calculated and given as Spearman's r and p-values.

Results: Kinetics of [177Lu]Lu-PSMA in mHSPC patients are comparable to those in mCRPC patients. Lesion absorbed dose was high (3.25 ± 3.19 Gy/GBq) compared to organ absorbed dose (salivary glands: 0.39 ± 0.17 Gy/GBq, kidneys: 0.49 ± 0.11 Gy/GBq, liver: 0.09 ± 0.01 Gy/GBq, bone marrow: 0.017 ± 0.008 Gy/GBq). A statistically significant correlation was found between treatment response and absorbed index lesion dose (p = 0.047).

Conclusions: We successfully performed small lesion dosimetry and showed that the tumor sink effect in mHSPC patients is of less concern than was expected. Tumor-to-organ ratio of absorbed dose was high and tumor uptake correlates with PSA response. Additional treatment cycles are legitimate in terms of organ toxicity and could lead to better tumor response.

Keywords: Dosimetry; Prostate cancer; Radionuclide therapy; [177Lu]Lu-PSMA; mHSPC.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Correlation between SUVmean/max on [68Ga]Ga-PSMA-PET/CT and absorbed dose in salivary glands (a) and lesions (b). Data of treatment cycles 1 and 2 are combined
Fig. 2
Fig. 2
The [177Lu]Lu-PSMA kinetics per cycle for index lesions in each patient. Blue lines represent lymph node lesions; purple lines represent bone lesions. Mono-exponential fits with R2 < 0.7 were excluded, and in these cases a trapezoidal method was used to determine the TIAC. In these cases, the fits are not shown in this figure (n = 5)
Fig. 3
Fig. 3
Absorbed dose in lymph node (LN) lesions was significantly higher than in bone lesions
Fig. 4
Fig. 4
Absorbed dose to index lesion for patients showing a PSA response of > 50% at the end of the study was significantly higher than for patients showing a response of < 50%. Blue circles indicate lymph node lesions; purple diamonds indicate bone lesions
See this image and copyright information in PMC

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