The lymphomas of the 27 enrolled patients (19 male, 8 female; age, 57.2 ± 13.1 year, range 15–76 year) 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 Fig. 1. The semiquantitative and visual comparisons of the lymphoma detected in 68Ga-Pentixafor and 18F-FDG PET/CT are shown in Table 2 and Fig. 2, respectively.
Table 1
Patients’ clinical characteristics and PET/CT diagnosis
No. | Age/sex | Type of lymphoma | Involvement | PET/CT diagnosis |
CXCR4 | 18F-FDG |
1 | 59/F | DLBCL | Cerebrum, ethmoidal sinus | P | P |
2 | 32/M | FL | LN, BM, spleen, lung | P | P |
3 | 53/M | iBCL | LN, BM, spleen | P | P |
4 | 60/M | DLBCL | Ileum | P | P |
5 | 64/M | EATL | Intestines | P | P |
6 | 50/M | EATL | Small intestines, BM | N | N |
7 | 60/F | iBCL | BM, spleen | P | P |
8 | 70/M | iBCL | BM, spleen | P | P |
9 | 71/M | MCL | LN | P | P |
10 | 64/M | DLBCL | Thyroid | P | P |
11 | 41/F | NKTCL | Nasal cavity, pharynx, LN, subcutaneous, BM | N | P |
12 | 52/F | NKTCL | Paranasal sinus, orbit, cerebrum | N | P |
13 | 15/M | PTCL-NOS | Musculature | N | P |
14 | 51/M | MZL | Lung | P | P |
15 | 65/F | MZL | Cerebral dura mater, kidney, retroperitoneum | P | P |
16 | 71/F | MZL | Lung, subcutaneous | P | P |
17 | 67/F | LPL | BM | P | N |
18 | 59/M | FL | LN | P | P |
19 | 58/M | LPL | BM, LN, liver, pancreas, PMD | P | P |
20 | 48/M | LPL | BM, LN, liver, PMD | P | P |
21 | 62/M | LPL | BM, LN | P | P |
22 | 74/M | EATL | Small intestines | P | P |
23 | 76/M | LPL | BM, LN | P | N |
24 | 56/F | MZL | Spleen | P | P |
25 | 51/M | LPL | BM, LN, PMD, pleura | P | N |
26 | 53/M | LPL | BM, LN | P | P |
27 | 64/M | LPL | BM, LN | P | P |
DLBCL = diffuse large B cell lymphoma; FL = follicular lymphoma; iBCL = indolent B cell lymphoma; EATL = enteropathy associated T cell lymphoma; MCL = mantle cell lymphoma; NKTCL = NK/T cell lymphoma; PTCL-NOS = peripheral T cell lymphoma, not otherwise specified; MZL = marginal zone lymphoma; LPL = lymphoplasmacytic lymphoma; LN = lymph nodes; BM = bone marrow, PMD = paramedullary disease. |
Table 2
Comparison of SUVmax and TBR in lymphomas
Type of lymphoma | SUVmax | | TBR |
CXCR4 | 18F-FDG | P | | CXCR4 | 18F-FDG | P |
LPL (n = 8) | 11.6 ± 3.2 | 3.2 ± 0.8 | 0.000* | | 6.5 ± 2.8 | 2.2 ± 0.7 | 0.003* |
MZL (n = 4) | 12.1 ± 5.0 | 5.3 ± 1.2 | 0.002* | | 6.2 ± 4.1 | 2.5 ± 0.6 | 0.05* |
DLBCL (n = 3) | 4.8 ± 1.7 | 14.9 ± 3.6 | 0.03* | | 2.8 ± 0.9 | 9.5 ± 3.6 | 0.04* |
FL (n = 2) | 7.6 ± 3.5 | 16.7 ± 0.5 | 0.33 | | 5.4 ± 4.2 | 14.2 ± 6.6 | 0.33 |
MCL (n = 1) | 6.2 | 10.1 | / | | 3.0 | 5.3 | / |
iBCL (n = 3) | 4.3 ± 1.8 | 4.2 ± 1.5 | 1.0 | | 1.9 ± 1.6 | 2.3 ± 1.9 | 0.7 |
PCTL-NOS (n = 1) | 1.3 | 7.8 | / | | 1.0 | 4.9 | / |
ETAL (n = 3) | 3.1 ± 1.9 | 2.2 ± 2.0 | 0.7 | | 1.7 ± 1.1 | 1.6 ± 1.0 | 0.7 |
NKTCL (n = 2) | 3.6 ± 0.1 | 14.2 ± 7.5 | 0.33 | | 1.3 ± 0.0 | 10.1 ± 6.9 | 0.33 |
* The difference of the uptake values between 68Ga-Pentixafor and 18F-FDG is significant. |
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 activity 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).