Abstract
242408
Introduction: CXCR4 targeted PET/CT with 68Ga-Pentixafor has provided an excellent detection rate for MM. However, in CXCR4-targeted endoradiotherapy, for pentixafor, an exchange of Ga3+ by Lu3+ or Y3+ ions will lead to significant loss of CXCR4 affinity. In CXCR4-directed theranostic concept, 177Lu- or 90Y-labelled probe Pentixather (3-iodo-D-Tyr1-pentixafor) is used as the therapeutic counterpart for 68Ga-Pentixafor diagnostic imaging. But Pentixather labeled with a diagnostic nuclide such as 68Ga has not yet be tested. In this prospective study, we aim to explore the possibility of using 68Ga-pentixather as the diagnostic PET agent in future CXCR4-directed theranostic concept for MM, and compare diagnostic performance with 68Ga-pentixafor PET/CT.
Methods: Patients with newly diagnosed MM were recruited. Patients underwent both 68Ga-pentixather PET/CT and 68Ga-pentixafor PET/CT within 1 week. Positive PET scan was defined as the presence of PET-positive focal bone lesions, paramedullary lesions, extramedullary lesions, or diffuse bone marrow uptake (higher than liver). The numbers and SUVmax of PET-positive lesions were recorded. PET-related tumor burden values (total bone marrow uptake [TBmU], SUVmax, and SUVmean) were obtained by drawing total bone marrow volume on PET/CT. The positive rate, lesion numbers, PET-related tumor burden values were compared between two groups. The correlations between PET-related tumor burden values and clinical stages were analyzed.
Results: Nineteen patients were enrolled in the present study. 68Ga-pentixather PET/CT was visually positive in 18/19 (94.7%) patients, while 68Ga-pentixafor PET/CT was positive in 15/19 (78.9%), without statistical significance. Four patients manifested as diffused bone marrow uptake without focal bone lesions or paramedullary disease. One of 4 patients showed positive diffused bone marrow on both two PET imaging, and 3 of 4 patients manifested as diffused bone marrow uptake on 68Ga-pentxiather PET/CT, but negative on 68Ga-pentixafor PET/CT. Fourteen patients showed multiple focal bone lesions on 68Ga-pentxiather PET/CT and 68Ga-pentixafor PET/CT. 68Ga-pentixather PET/CT detected more focal bone lesions in 5 of 14 patients (Figure 1. A-E) than 68Ga-pentxiafor PET/CT, while 68Ga-pentxiafor PET/CT detected more focal bone lesions in 1 of 14 patients (Figure 1. F) than 68Ga-pentixather, the other 8 of 14 patients had equal numbers of focal bone lesions on two PET imaging. A total of 151 matched focal bone marrow lesions were revealed on the two PET imaging. 68Ga-pentixather PET/CT demonstrated significant higher uptake value of focal bone marrow lesions than 68Ga-pentixafor PET/CT [SUVmax, 16.8 (9.0, 23.8) vs. 13.4 (6.5, 20.4), p < 0.001]. For paramedullary disease, 68Ga-pentixather PET/CT and 68Ga-pentixafor PET/CT both detected 8 paramedullary lesions in 4 patients. No extramedullary disease was found.
Then quantitative analysis of PET related-tumor burden was performed (Figure 2. A-B). Similar total bone marrow volume of two scans in each patient was delineated (p=0.263). Significant higher TBmU, SUVmean and SUVmax of total bone marrow were demonstrated on 68Ga-pentixather PET/CT than 68Ga-pentixafor PET/CT [TBmU, 7864.9 (5549.2, 11616.2) vs. 5383.39 (4102.7, 11041.8), p<0.001; SUVmean, 1.4 (1.1, 2.2) vs. 1.1 (0.7, 2.1), p<0.001; SUVmax, 16.4 (8.9, 31.5) vs. 9.4 (4.1, 24.0), p=0.001]. For correlation analysis, we observed a significant correlation of the TBmU between the two scans (r=0.9540, p<0.0001, figure 2-C). SUVmean of bone marrow uptake on 68Ga-pentixather PET/CT correlated well with that of 68Ga-pentixafor PET/CT (r=0.9632, p < 0.0001, figure 2-D). Comparing the PET related-tumor burden between different clinical stages, there was significant increasing 68Ga-pentixather TBmU (p=0.0025, figure 3-E) and 68Ga-pentixafor TBmU (p=0.0049, figure 2-F) in DSS III stage than DSS I stage (no patient was DSS II stage).
Conclusions: The positive rate of 68Ga-pentixather PET/CT was superior or at least equal to 68Ga-pentixafor PET/CT in newly diagnosed MM. 68Ga-pentixather PET/CT can assess tumor load in MM patients and depict a significantly higher PET-related total tumor burden than 68Ga-pentixafor PET/CT.
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