The lymphomas of the 27 enrolled patients (19 male, 8 female; age, 57.2±13.1 yr, range 15-76 yr) included lymphoplasmacytic lymphoma (n = 8), marginal zone lymphoma (n = 4), peripheral T cell lymphoma (n = 4), DLBCL (n = 3), unclassified indolent B cell lymphoma (n = 3), follicular lymphoma (n = 2), NK/T cell lymphoma (n = 2), and mantle cell lymphoma (n = 1). The patients did not receive any treatment against lymphoma before PET/CT scans. Clinical characteristics of the recruited patients and the diagnostic performance of dual-tracer PET/CT in each case are given in Table 1, and examples of maximum intensity projections of the dual-tracer PET scans in lymphomas are shown in Figure 1. The semiquantitative and visual comparisons of the lymphoma detected in [68Ga]pentixafor and [18F]FDG PET/CT are shown in Table 2 and Figure 2, respectively.
Lymphoplasmacytic lymphoma
Bone marrow is the predominant site of involvement in lymphoplasmacytic lymphoma, which was confirmed by bone marrow aspiration and biopsy in all recruited patients. On [68Ga]pentixafor PET/CT, all 8 patients had intense radioactivity in the bone marrow, with an SUVmax of 9.5 ± 2.6 (range, 7.0-14.8). With [18F]FDG PET/CT, the bone marrow intensity was comparable to the uptake in liver (SUVmax 2.1-4.6). In comparisons of [68Ga]pentixafor and [18F]FDG, all 8 patients had visually higher uptake in the bone marrow on [68Ga]pentixafor PET than on [18F]FDG PET. Regarding the extent of bone marrow involvement, [68Ga]pentixafor PET demonstrated more extensive bone marrow disease in 6 patients than [18F]FDG PET, specifically when the involvement of the craniofacial bones and distal upper extremity bones was visualized.
[68Ga]pentixafor PET/CT detected positive lymph node involvements in 7 patients (SUVmax 11.3 ± 3.5, range 6.9-16.9), and 6 patients had involvement in more than 5 lymph node regions. However, with [18F]FDG PET/CT, only 3 patients were found to have mildly FDG-avid lymph nodes (SUVmax 1.2-4.7). Moreover, [68Ga]pentixafor PET/CT detected more positive lymph nodes with higher radioactivity in these 3 patients than [18F]FDG PET/CT. Additionally, [68Ga]pentixafor detected disease of paramedullary involvements, liver, pancreas, and pleura in 3 patients; however, the above lesions were missed in [18F]FDG PET. The SUVmax and TBR of the matched disease in bone marrow, lymph node, and other involvements were significantly higher in [68Ga]pentixafor PET than in [18F]FDG PET (paired Student t-test, p < 0.01).
Marginal zone lymphoma
Four patients were confirmed with marginal zone lymphoma at histology, including 3 patients with MALT lymphoma and 1 patient with splenic marginal zone lymphoma. The 3 patients with MALT lymphoma had disease involved the lung, kidney, retroperitoneum, subcutaneous area, and cerebral dura mater. [68Ga]pentixafor PET/CT showed intense radioactivity in the above lesions, with an SUVmax of 13.2 ± 4.1 (range, 8.9-20.3). With [18F]FDG PET/CT, the MALT lymphoma involvements were hypermetabolic (SUVmax 4.1-5.5), but the uptake and TBR of [18F]FDG was significantly lower than that of [68Ga]pentixafor (paired Student t-test, p < 0.05). Furthermore, [68Ga]pentixafor PET also detected disease in cerebral dura mater with intense [68Ga]pentixafor uptake in one patient, which was not shown in [18F]FDG PET. The patient with splenic marginal zone lymphoma had solitary disease in the spleen, which showed comparative uptake of both tracers (SUVmax, [68Ga]pentixafor vs. [18F]FDG, 5.5 vs. 7.5).
Diffuse large B cell lymphoma
Three patients were diagnosed with DLBCL affecting the cerebrum, ethmoid sinus, ileum, and thyroid. [68Ga]pentixafor PET/CT showed increased uptake of [68Ga]pentixafor in these lesions; however, the intensity of radioactivity in [68Ga]pentixafor PET was significantly lower than that in [18F]FDG PET (SUVmax, [68Ga]pentixafor vs. [18F]FDG, 4.8 ± 1.7 vs. 14.9 ± 3.6, p = 0.030). It is noteworthy that although the uptake of [68Ga]pentixafor in the cerebral DLBCL was lower than the uptake of [18F]FDG in this lesion, the visual assessment of the disease in [68Ga]pentixafor PET and [18F]FDG PET was comparable due to the low background radioactivity of [68Ga]pentixafor in the brain (TBR in [68Ga]pentixafor PET is much higher than the TBR in [18F]FDG PET if normal cerebrum regarded as background [TBR, 10.8 vs. 1.6]).
Follicular lymphoma
The 2 patients with follicular lymphoma had disease involved the lymph nodes, spleen, lung, and bone marrow. In one patient with follicular lymphoma (WHO grade 1-2) involving a few lymph nodes, the radioactivity of the lesions and the extension of the disease detected in [68Ga]pentixafor PET and [18F]FDG PET were similar. In another patient with follicular lymphoma (WHO grade 3B) that was extensively involved the lymph nodes, spleen, lung, and bone marrow, the [68Ga]pentixafor uptake in the lymphoma lesions were increased, however it was much lower than the [18F]FDG uptake in these lesions (SUVmax, [68Ga]pentixafor vs. [18F]FDG, 5.1 vs. 17.0).
Mantle cell lymphoma
Only one patient had mantle cell lymphoma, which involved multiple lymph node regions. The involved lymph nodes had moderately increased uptake of [68Ga]pentixafor (SUVmax 6.2), but was lower than the uptake intensity of [18F]FDG (SUVmax 10.1).
Indolent B cell lymphoma, unclassified
Unclassified indolent B cell lymphoma was confirmed in 3 patients, who had involvement in bone marrow, spleen, and a few lymph nodes. Both [68Ga]pentixafor PET and [18F]FDG PET showed mild to moderate radioactivity in the lymphoma involvements.
Peripheral T cell lymphoma
Three patients were diagnosed with enteropathy associated T cell lymphoma (EATL). In 2 patients with EATL, both [68Ga]pentixafor PET and [18F]FDG PET showed mildly increased radioactivity in the intestines, however the dual-tracer PET/CT results were both false negative in the remaining one patient with EATL. One patient had peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) involving musculature. The disease had intense uptake of [18F]FDG (SUVmax 7.8), however it was not avid for [68Ga]pentixafor (SUVmax 1.3).
NK/T cell lymphoma
Two patients were diagnosed with NK/T cell lymphoma, affecting the nasal cavity, paranasal sinus, orbit, cerebrum, pharynx, lymph node, subcunaneous area, and bone marrow. The uptake of [68Ga]pentixafor in these lesions was not increased; meanwhile the lesions were very FDG-avid (SUVmax, [68Ga]pentixafor vs. [18F]FDG, 3.6 vs. 19.5).