Kidney dosimetry in ¹⁷⁷Lu and ⁹⁰Y peptide receptor radionuclide therapy: influence of image timing, time-activity integration method, and risk factors

Abstract

Kidney dosimetry in (177)Lu and (90)Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with (177)Lu DOTATATE and 30 with (177)Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6 h and the 3 d points. We found that data should be collected until 100 h for (177)Lu therapy and 70 h for (90)Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (t-test, P < 0.10), with DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05).

Figure 1

Examples of observed pharmacokinetic behaviour: with-accumulation (blue line, pt no. 45), single-slope clearance (red line, pt no. 43), two-slope clearance (violet line, pt no. 38).

Figure 2

¹⁷⁷Lu (a) and ⁹⁰Y (b) time-integrated activities $\tilde{a}$ in hours for methods TRph, TRexp, BI, MN, MNfix, VIS, FT. Boxes draw the 25th percentile (lower box bound, indicating 25th of data fall below it), 50th percentile (i.e., median value), and 75th percentile (upper box bound). Crosses indicate outliers defined as observations out of 1.5 · (75th percentile value −25th percentile value). Whiskers extend to the most extreme values that are not outliers.

Figure 3

Relative difference of $\tilde{a}$ values for ¹⁷⁷Lu-DOTATATE between MN and BI methods $y=({\tilde{a}}_{\text{MN}}-{\tilde{a}}_{\text{BI}}\mathrm{\hspace{0.17em}\hspace{0.17em}})/{\tilde{a}}_{\text{BI}}$ plotted against the relative difference of the squared residuals SSE x = (SSE_MN − SSE_BI)/SSE_BI.

Figure 4

¹⁷⁷Lu ${\tilde{a}}_{\text{FT}}$ and ${\tilde{a}}_{\text{VIS}}$ for the cases in which there was a discrepancy greater than 10% between the visual and the F-test (8 cases for TATE, 11 for TOC).

Figure 5

(a) pt no. 35 ¹⁷⁷Lu DOTATATE: MNfix and BI obtained with all experimental points (red and violet lines, resp.) and MN and BI skipping the 3 d point (green and blue lines, resp.); (b) pt no. 45 ¹⁷⁷Lu DOTATOC: MN and BI obtained with all experimental points (red and violet lines, resp.) and BI skipping the 6 h point (blue line).

Figure 6

D and BED in case of ¹⁷⁷Lu therapy (upper panels) and ⁹⁰Y therapy (lower panels). The histograms report mean and 1 SD. ¹⁷⁷Lu and ⁹⁰Y-therapy administer a similar total dose for the specific schemes considered (29.8 GBq in 4 cycles versus 7.4 GBq in 2 cycles, resp.). Conversely, BED is noticeably greater for ⁹⁰Y because of the lower fractionation. Mean ± SD values are similar, but relevant differences among patients can be found (see also Figure 4).

Figure 7

Time-integrated activity per unit activity $\tilde{a}$ for patients with risk factors (RF) (diamonds) and without (NRF) (dots). For each population, the mean value is indicated by the horizontal line, and the box extends to mean ± SD. For DOTATATE, 11 patients were RF and 17 NRF, and the P-values of t-test were 0.05 and 0.06, for ¹⁷⁷Lu and ⁹⁰Y, respectively. For DOTATOC, 12 patients were RF and 17 NRF (one outlier was excluded), and P-values were 0.09 and 0.06, for ¹⁷⁷Lu and ⁹⁰Y, respectively.