Bone Marrow Absorbed Doses and Correlations with Hematologic Response During ¹⁷⁷Lu-DOTATATE Treatments Are Influenced by Image-Based Dosimetry Method and Presence of Skeletal Metastases

Abstract

This study aimed to compare different image-based methods for bone marrow dosimetry and study the dose–response relationship during treatment with 177Lu-DOTATATE in patients with and without skeletal metastases. Methods: This study included 46 patients with advanced neuroendocrine tumors treated with at least 2 fractions of 177Lu-DOTATATE at Sahlgrenska University Hospital. High- and low-uptake compartments were automatically outlined in planar images collected at 2, 24, 48, and 168 h after injection. The bone marrow absorbed doses were calculated from the cross doses of the high- and low-uptake compartments and the self-dose, using the time–activity concentration curve for the low-uptake compartment. This time–activity concentration curve was adjusted using a fixed constant of 1.8 for the planar dosimetry method and using the activity concentrations in vertebral bodies in SPECT images at 24 h after injection of 177Lu-DOTATATE in 4 hybrid methods: L4-SPECT used the activity concentration in the L4 vertebra, whereas V-SPECT, L-SPECT, and T-SPECT used the median activity concentration in all visible vertebrae, lumbar vertebrae, and thoracic vertebrae, respectively. Results: Using the planar method, L4-SPECT, V-SPECT, L-SPECT, and T-SPECT, the estimated median bone marrow absorbed doses were 0.19, 0.36, 0.40, 0.39, and 0.46 Gy/7.4 GBq, respectively, with respective ranges of 0.12–0.33, 0.15–1.44, 0.19–1.71, 0.21–1.60, and 0.18–2.12 Gy/7.4 GBq. For all methods, the bone marrow absorbed dose significantly correlated with decreased platelet counts. This correlation increased after treatment fraction 2: the Spearman correlation (rs) were −0.49 for the planar method, −0.61 for L4-SPECT, −0.63 for V-SPECT, −0.63 for L-SPECT, and −0.57 for T-SPECT. A separate analysis revealed an increased correlation for patients without skeletal metastases using the planar method (rs = −0.67). In contrast, hybrid methods had poor correlations for patients without metastases and stronger correlations for patients with skeletal metastases (rs = −0.61 to −0.74). The mean bone marrow absorbed doses were 3%–69% higher for patients with skeletal metastases than for patients without. Conclusion: The estimated bone marrow absorbed doses by image-based techniques and the correlation with platelets are influenced by the choice of measured vertebrae and the presence of skeletal metastases.

Deep-Learning Generation of Synthetic Intermediate Projections Improves 177Lu SPECT Images Reconstructed with Sparsely Acquired Projections

“…Nevertheless, a recent prospective dosimetry study demonstrated that an increased number of treatments can be given based on total absorbed kidney dose (3), thereby avoiding undertreatment. In addition, doseresponse relationships have been reported for the dose-limiting organs kidneys and bone marrow, indicating the potential for dosimetry as one important factor in the individualized treatment protocol (4,5).…”

The increasing potential of nuclear medicine imaging for the evaluation and reduction of normal tissue toxicity from radiation treatments

“…Owing to the theragnostic nature of the 177 Lu-DOTA-TATE molecule, SPECT images can also be made alongside its therapeutic action to verify in vivo dosimetry and biodistribution. Two studies used this principle and found the estimated dose to the bone marrow to be much higher than blood-based dosimetry methods [36,37]. One of them also showed correlations between bone marrow dose, and reduction in platelet counts [37].…”

“…Two studies used this principle and found the estimated dose to the bone marrow to be much higher than blood-based dosimetry methods [36,37]. One of them also showed correlations between bone marrow dose, and reduction in platelet counts [37]. RNTs are usually delivered over multiple cycles, and these post-therapy scans can be used to plan subsequent therapy cycles and even assess potential toxicity between them.…”

PRRT of neuroendocrine tumors: individualized dosimetry or fixed dose scheme?

“…A reason for this finding might be the high variability of bone marrow dose depending on the method used. SPECT-based activity concentration fluctuated 100% (L5 median 24.2 kBq/ml, T11 median 47.8 kBq/ml) depending on the vertebral body examined [7]. Consequently, bone marrow doses varied depending on the used method: planar scintigraphy 0.19 Gy/7.4 GBq, SPECT of L4 0.36 Gy/ 7.4 GBq, SPECT of all visible vertebra 0,40 Gy/7.4 GBq, SPECT of all lumbar vertebra 0.39 Gy/7.4 GBq, and SPECT of all thoracic vertebra 0.46 Gy/7.4 GBq.…”