Summary

Background Internal dosimetry in individual patients is essential for safe and effective radioligand therapy. Multiple time point imaging for accurate dosimetry is time consuming and hence can be demanding for nuclear medicine departments as well as patients. The objectives of this study were (1) to assess absorbed doses to organs at risk and tumor lesions for [177Lu]Lu-PSMA-I&T using whole body SPECT imaging and (2) to investigate possible simplified dosimetry protocols. Methods This study included 16 patients each treated with 4 cycles of [177Lu] Lu-PSMA-I&T.

They underwent quantitative whole body SPECT/CT imaging (3 bed positions) at four time points (TP) comprising 2 h, 24 h, 48 h and 72–168 h postinjection (p.i.). Full 3D dosimetry (reference method) was performed for all patients and dose cycles for organs at risk (kidneys, parotid glands and submandibular glands) and up to ten tumor lesions per patient (resulting in 90 lesions overall).

The simplified dosimetry methods (SM) included (1) generating time activity curves for subsequent cycles using a single TP of imaging applying the kinetics of dose cycle 1, and for organs at risk also (2) simple extrapolation from dose cycle 1 and (3) from both, dose cycle 1 and 2. Results Normalized absorbed doses were 0.71±0.32 mGy/MBq, 0.28±0.12 mGy/ MBq and 0.22±0.08 mGy/MBq for kidneys, parotid glands and submandibular glands, respectively. Tumor doses decreased from 3.86±3.38 mGy/MBq in dose cycle 1 to 2.01±2.65 mGy/MBq in dose cycle 4.

Compared to the full dosimetry approach the SM 1 using single TP imaging at 48 h p.i. resulted in the most accurate and precise results for the organs at risk in terms of absorbed doses per cycle and total cumulated dose. For tumor lesions better results were achieved using the fourth TP (≥72 h p.i.). Conclusion Simplification of safety dosimetry protocols is possible for [177Lu]Lu-PSMAI&T therapy. If tumor dosimetry is of interest a later imaging TP (≥72 h p.i.) should be used/added to account for the slower kinetics of tumors compared to organs at risk.

Keywords: Radioligand therapy, Prostate cancer, 177Lu-PSMA, Dosimetry, Tumor dosimetry, [177Lu]Lu-PSMA-I&T, Single time point

Results from: AnyScan TRIO ^® SPECT/CT

For each patient, whole-body SPECT/CT scans were acquired (3 bed positions from the eye socket to the upper thighs; 90 projections a’ 20  s, energy window: 208  keV±10%) on a AnyScan Trio ^® SPECT/CT  (Mediso, Budapest, Hungary) at four time points (TP) at 2 h, 24 h, 48 h and 72 h to 168 h (mean 130 h) post-injection (p.i.). The scanner was equipped with a medium-low-energy general purpose (MLEGP) collimator. Quantitative image reconstruction was performed using the manufacturer’s Tera-Tomo™ 3D SPECT OSEM reconstruction with 110 effective iterations and 5 subsets applying CT-based attenuation correction, Monte Carlo-based scatter correction, and resolution recovery. To yield quantitative images (Bq/mL) a calibration factor was determined from an initial phantom experiment and automatically applied to each patient SPECT dataset.

Table 1. Patient characteristics.

Fig. 1 Box-Whisker-Plots showing the quartiles, the 5th and 95th percentiles (whiskers) and the mean (+) of the normalized absorbed doses (Normalized D) based on the RM across patients for kidneys (A), parotid glands (B) and submandibular glands (C). The course of values for each patient over the first four treatment cycles is shown for kidneys (D), parotid glands (E) and submandibular glands (F).

Table 4. Results of the bland-Altman analysis and RMSE comparing RM to SM1 using single time-point imaging at 2–4, 24, 48 and 72–168 h p.i. combined for treatment cycles 2 to 4 for organs at risk (kidneys, parotid glands and submandibular glands) and tumor lesions (individual tumor lesions and the mean of tumor lesions per patient).

Fig 6. Bland-Altman plots for total cumulated absorbed dose over all 4 dose cycles for organs at risk comparing RM to SM1 (at 48 h p.i.; A), to SM 2 (B) and to SM 3 (C). The green line represents the mean bias between the two methods, the red lines show the 95% limits of agreement.

Conclusion:

The absorbed doses reported here for [177Lu]Lu-PSMA-I&T were overall in the range of those reported previously for [177Lu]Lu-PSMA-617 and also [177Lu]Lu-PSMA-I&T for kidneys, salivary glands and tumors. In our study the kidneys were the major organ at risk. For the prediction of absorbed dose using single time point imaging at 48 h p.i. starting from dose cycle 2 is feasible for safety dosimetry for [177Lu]Lu-PSMA-I&T. It would also be sufficient to extrapolate the dose for later dose cycles based on the injected activity and dosimetry results using full dosimetry imaging at dose cycles 1 and 2. Extrapolation from dose cycle 1 alone is possible but gave results with limited accuracy and should be applied with caution only if no other options are available.

For tumor dosimetry single time point imaging at or beyond 72  h p.i. may be possible for individual treatment planning, but further research using additional and consistent late time points would be needed to determine the most suitable time point. Simple extrapolations based on injected activity and dosimetry results at early dose cycles cannot be used for tumors due to the observed reduction of activity uptake and tumor dose in later dose cycles. Altogether it was shown that simplified dosimetry methods are feasible for [177Lu] Lu-PSMA-I&T with the capacity of reducing the burden on clinical departments and patients while allowing for safe and potentially more effective radioligand therapies for individual patients.

Original link: ejnmmiphys.springeropen.com