Dosimetry for Lu-177-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer

Purpose Dosimetry is critical to achieve the optimal therapeutic effect of radioligand therapy (RLT) with limited side effects. Our aim was to perform image-based absorbed dose calculation for the new PSMA ligand Lu-177-DKFZ-PSMA-617 in support of its use for the treatment of metastatic prostate cancer. Methods Whole-body planar images and SPECT/CT images of the abdomen were acquired in five patients (mean age 68 years) for during two treatment cycles at approximately 1, 24, 48 and 72 h after administration of 3.6 GBq (range 3.4 to 3.9 GBq) Lu-177-DKFZ-PSMA-617. Quantitative 3D SPECT OSEM reconstruction was performed with corrections for photon scatter, photon attenuation and detector blurring. A camera-specific calibration factor derived from phantom measurements was used for quantitation. Absorbed doses were calculated for various organs from the images using a combination of linear approximation, exponential fit, and target-specific S values, in accordance with the MIRD scheme. Absorbed doses to bone marrow were estimated from planar and SPECT images and with consideration of the blood sampling method according to the EANM guidelines. Results The average (+/- SD) absorbed doses per cycle were 2.2 +/- 0.6 Gy for the kidneys (0.6 Gy/GBq), 5.1 +/- 1.8 Gy for the salivary glands (1.4 Gy/GBq), 0.4 +/- 0.2 Gy for the liver (0.1 Gy/GBq), 0.4 +/- 0.1 Gy for the spleen (0.1 Gy/GBq), and 44 +/- 19 mGy for the bone marrow (0.012 Gy/GBq). The organ absorbed doses did not differ significantly between cycles. The critical absorbed dose reported for the kidneys (23 Gy) was not reached in any patient. At 24 h there was increased uptake in the colon with 50 - 70 % overlap to the kidneys on planar images. Absorbed doses for tumour lesions ranged between 1.2 and 47.5 Gy (13.1 Gy/GBq) per cycle. Conclusion The salivary glands and kidneys showed high, but not critical, absorbed doses after RLT with Lu-177-DKFZ-PSMA-617. We suggest that Lu-177-DKFZ-PSMA-617 is suitable for radiotherapy, offering tumour-to-kidney ratios comparable to those with RLT agents currently available for the treatment of neuroendocrine tumours. Our dosimetry results suggest that Lu-177-DKFZ-PSMA-617 treatment with higher activities and more cycles is possible without the risk of damaging the kidneys.