Differences in tumor-to-normal organ SUV ratios measured with 68 Ga-DOTATATE PET compared with 177 Lu-DOTATATE SPECT in patients with neuroendocrine tumors

Abstract

Background: Our goal is to quantitatively compare radiotracer biodistributions within tumors and major normal organs on pretherapy 68 Ga-DOTATATE PET to post-therapy 177 Lu-DOTATATE single-photon emission computed tomography (SPECT) in patients receiving peptide receptor radionuclide therapy (PRRT).

Methods: PET/CT at ~ 60 min postinjection of Ga-68 DOTATATE and research 177 Lu-SPECT/CT imaging ~ at 4 h (SPECT1) and ~ 24 h (SPECT2) post-cycle#1 were available. Manual contours of lesions on baseline CT or MRI were applied to co-registered SPECT/CT and PET/CT followed by deep learning-based CT auto-segmentation of organs. Tumor-to-normal organ ratios (TNR) were calculated from standardized uptake values (SUV) mean and SUV peak for tumor, and SUV mean for non-tumoral liver (nliver), spleen and kidney.

Results: There were 90 lesons in 24 patients with progressive metastatic neuroendocrine tumor. The correlation between PET and SPECT SUV TNRs were poor/moderate: PET versus SPECT1 R 2 = 0.19, 0.21, 0.29; PET versus SPECT2 R 2 = 0.06, 0.16, 0.33 for TNR nliver ,TNR spleen ,TNR kidney , respectively. Across all patients, the average value of the TNR measured on PET was significantly lower than on SPECT at both time points ( P < 0.001). Using SUV mean for tumor, average TNR values and 95% confidence intervals (CI) were PET: TNR nliver = 3.5 [CI: 3.0-3.9], TNR spleen = 1.3 [CI, 1.2-1.5], TNR kidney = 1.7 [CI: 1.6-1.9]; SPECT1: TNR nliver = 10 [CI: 8.2-11.7], TNR spleen = 2.9 [CI: 2.5-3.4], TNR kidney = 2.8 [CI: 2.3-3.3]; SPECT2: TNR nliver = 16.9 [CI: 14-19.9], TNR spleen = 3.6 [CI: 3-4.2], TNR kidney = 3.6 [CI: 3.0-4.2]. Comparison of PET and SPECT results in a sphere phantom study demonstrated that these differences are not attributed to imaging modality.

Conclusions: Differences in TNR exist for the theranostic pair, with significantly higher SUV TNR on 177 Lu SPECT compared with 68 Ga PET. We postulate this phenomenon is due to temporal differences in DOTATATE uptake and internalization in tumor as compared to normal organs.

FIGURE 1.

Baseline diagnostic images used to define lesions and co-registered pre-therapy ⁶⁸Ga-DOTATATE PET/CT and post-therapy ¹⁷⁷Lu-DOTATATE SPECT/CT images demonstrating higher uptake in tumor relative to normal organs in the SPECT images compared with the PET image. The maximum intensity projections (MIP) with lesions (red), normal liver (green), kidney (blue) and spleen (magenta) VOIs used to extract SUV metrics are also shown. A) Patient L20 with a 29 mL hepatic lesion. TNR_nliver: PET = 2.0, SPECT1 = 21.2, SPECT2 = 32.4; TNR_spleen: PET = 1.0, SPECT1 = 7.9, SPECT 2 = 8.8; TNR_kidney: PET = 1.5, SPECT 1 = 6.6, SPECT 2 = 6.5. B) Patient L14 with a 1045 mL hepatic lesion. TNR_nliver: PET = 1.3, SPECT 1 = 11.3, SPECT2 = 17.2; TNR_spleen: PET = 0.8, SPECT1 = 6.2, SPECT 2 = 6.1; TNR_kidney: PET = 0.8, SPECT1 = 2.9, SPECT2 = 3.0. This patient also has a large mesenteric lymph node evident on the MIP. PET and SPECT images are displayed on the same SUV scale.

FIGURE 2.

SUV values measured at the first (~ 4 h p.i.) ¹⁷⁷Lu SPECT/CT imaging time point versus SUV values measured on 1 h p.i. ⁶⁸Ga PET/CT. The points in red indicate lesions outside the liver. The line of equivalence is indicated in black. SUV values measured at the second (~ 24 h p.i.) ¹⁷⁷Lu SPECT/CT imaging time point versus SUV values measured on 1 h p.i. ⁶⁸Ga PET/CT are shown in Supplemental Figure 1.

FIGURE 3.

Tumor-to-normal organ SUV ratios (calculated using tumor SUV_mean) measured on SPECT vs. PET. The points in red indicate lesions outside the liver. Tumor-to-normal organ SUV ratios (calculated using tumor SUV_peak) measured on SPECT vs. PET are shown in Supplemental Figure 2.

FIGURE 4.

Phantom results comparing ⁶⁸Ga PET and ¹⁷⁷Lu SPECT images and sphere-to-background SUV ratios. The SPECT versus PET Pearson correlation R² value for SUV_mean is 0.99 and for SUV_peak is 0.75. The true sphere-to-background SUV ratio is 6.2 for the ¹⁷⁷Lu phantom and 6.4 for the ⁶⁸Ga phantom. Data points from left to right correspond to 2, 4, 8, 16, 30, and 114 mL spheres.