Visual Abstract
Abstract
Our objective was to compare the diagnostic performance of 68Ga-labeled fibroblast activation protein (FAP) inhibitor (FAPI) and 18F-labeled FDG PET/CT in diagnosing lymphomas and to characterize the influence of FAP and glycolytic markers on tracer uptake by involved lesions. Methods: Participants with different lymphoma subtypes who were prospectively recruited from May 2020 to December 2021 underwent 68Ga-FAPI and 18F-FDG PET/CT. Immunohistochemistry was performed to evaluate FAP, hexokinase 2, and glucose transporter 1 (GLUT1) expression, and the paired-samples t test and Wilcoxon signed-rank test were used to compare parameters. The correlation between the immunochemistry results and tracer uptake was determined by the Spearman rank correlation coefficient. Results: In total, 186 participants (median age, 52 y [interquartile range, 41–64 y]; 95 women) were included. Dual-tracer imaging produced 3 types of imaging profiles. 18F-FDG PET possessed a higher staging accuracy (98.4%) than 68Ga‐FAPI PET (86.0%). In 5,980 lymphoma lesions, 18F-FDG PET/CT detected more nodal (4,624 vs. 2,196) and extranodal (1,304 vs. 845) lesions than 68Ga-FAPI PET/CT. Additionally, 52 68Ga-FAPI–positive/18F-FDG–negative lesions and 2,939 68Ga-FAPI–negative/18F-FDG–positive lesions were observed. In many lymphoma subtypes, semiquantitative evaluation revealed no significant differences in SUVmax or target-to-liver ratios between 68Ga-FAPI and 18F-FDG PET/CT (P > 0.05). Interestingly, GLUT1 and hexokinase 2 were overexpressed both in lymphoma cells and in the tumor microenvironment, whereas FAP was expressed only in stromal cells. FAP and GLUT1 expression correlated positively with 68Ga-FAPI SUVmax (r = 0.622, P = 0.001) and 18F-FDG SUVmax (r = 0.835, P < 0.001), respectively. Conclusion: 68Ga-FAPI PET/CT was inferior to 18F-FDG PET/CT in diagnosing lymphomas with low FAP expression. However, the former may supplement the latter and help reveal the molecular profile of lymphomas.
Lymphomas are a heterogeneous group of lymphoproliferative disorders that include Hodgkin lymphoma (HL) and non-Hodgkin lymphoma. Despite the structural and molecular differences between lymphoma subtypes, it is well recognized that the tumor microenvironment (TME) plays a critical role in lymphoma survival and growth (1–3). Recent progress has enhanced our knowledge of the pivotal role of cancer-associated fibroblasts (which are a prominent component of the TME and overexpress fibroblast activation proteins [FAPs]) in potentially regulating tumor progression in hematologic neoplasms via cell-to-cell interactions and secretion of different molecules (4). The role is even more prominent given the swathes of FAP-based theranostics entering the clinical arena (5,6).
In preliminary studies, positive expression of FAPs was detected in different lymphoma subtypes via 68Ga-labeled FAP inhibitor (FAPI) PET/CT, and the relationship between the histologic subtype and 68Ga-FAPI avidity was identified (7–9). Moreover, in those studies, the reduced background activity favored the use of 68Ga-FAPI PET/CT in evaluating involvement of the brain, liver, and head and neck regions.
Lymphoma cells demonstrate increased glucose metabolism, which is due, in part, to an increased number of glucose transporter proteins and increased intracellular enzyme levels of hexokinase and phosphofructokinase, which promote glycolysis (10). This process has underpinned the success of 18F-labeled FDG PET/CT in most lymphomas. Currently, 18F-FDG PET/CT is integral in managing patients with lymphomas, particularly in locating lesions, performing staging, detecting relapse, and monitoring tumor therapy.
This prospective study aimed to compare the diagnostic performance of 68Ga-FAPI and 18F‐FDG PET/CT in depicting different lymphoma subtypes and to explore the histologic mechanism of the dual-tracer imaging profiles. We hypothesized that 68Ga-FAPI PET/CT can be an alternative to 18F-FDG PET/CT for lymphoma imaging.
MATERIALS AND METHODS
Study Participants
This study conformed with the principles of the Declaration of Helsinki, was approved by the Institutional Review Board of our hospital (approval 2019KT95), and was registered with ClinicalTrials.gov (NCT04367948). We consecutively recruited participants with lymphomas from May 2020 to December 2021, and all participants provided written informed consent. The participant inclusion criteria were as follows: a pathologic diagnosis of lymphoma, an age of 18–75 y, expected survival of at least 12 wk, and at least 1 target lesion with 68Ga-FAPI uptake. The exclusion criteria were as follows: severe liver or kidney dysfunction, pregnancy or lactation, an inability to lie on the scanner bed for 0.5 h, and an inability or unwillingness (on the part of either the participant or a legal representative) to provide written informed consent. The final study cohort comprised 186 participants, including 61 participants with a previously reported 68Ga-FAPI PET/CT study (7).
68Ga-FAPI and 18F-FDG Preparation
68Ga-FAPI and 18F-FDG were synthesized and radiolabeled as previously described (7). Both had more than 95% radiochemical purity. The final products were diluted with saline and sterilized by being passed through a 0.22-μm Millex-LG filter (EMD Millipore) before injection.
PET/CT Imaging
The participants underwent 18F-FDG and 68Ga-FAPI PET/CT on separate days within 7 d. After fasting for 6 h, their blood glucose level was measured before 18F-FDG PET/CT scanning to ensure that it was less than 10 mmol/L. For 68Ga-FAPI PET/CT scanning, no specific preprocedural preparation was required. We administered 18F-FDG and 68Ga-FAPI intravenously at 3.7 and 1.8–2.2 MBq/kg, respectively. At approximately 60 ± 10 min after injection, an acquisition was initiated at 6–8 bed positions (1 min/bed position) using a hybrid system (Philips Gemini TF PET/CT scanner) that covered the base of the skull to the upper thigh. Non–contrast-enhanced CT was performed for attenuation correction and anatomic localization using the following parameters: 100-mA modulation, 120 kV, and 3-mm slice thickness. The dedicated head acquisition was separately conducted at 1 bed position (8–10 min/bed position). Emission data were corrected for random events, scatter, and decay. The data were reconstructed using ordered-subset expectation maximum to obtain coronal, sagittal, and cross-sectional PET and PET/CT images (7). Additionally, the participants were asked to self-report any abnormalities at 30 min after 68Ga-FAPI PET/CT scanning.
Image Analysis
Two of the authors who have 8 and 10 y of experience in nuclear oncology independently reviewed the 68Ga-FAPI PET/CT images, and 2 other authors who have 7 and 20 y of experience in nuclear oncology independently reviewed the 18F-FDG PET/CT images. Any disagreement was resolved by consensus. PET, CT, and PET/CT images were viewed using a Philips EBW workstation. The lesions were classified as nodal or extranodal according to the Lugano classification (11). The presence and sites of lymphoma involvement and the intensity of 68Ga-FAPI or 18F-FDG uptake in the lesions were recorded for each PET scan. Increased radioactivity compared with the background uptake was considered positive. Positive lesions were finally determined by consensus analysis of histology, morphologic imaging, and follow-up routine imaging examinations. Subsequent quantification of tumor uptake was based on the SUVmax via the region-of-interest technique. We also quantified the nonspecific background uptake in the liver within a 2-cm-diameter sphere and calculated the target-to-liver ratio (TLR).
Immunohistochemical Analysis
The expression of FAP in lymphoma lesions was evaluated in 25 postsurgical and 37 biopsy samples, comprising 9 with HL and 53 with non-Hodgkin lymphoma (26 diffuse large B-cell lymphoma [DLBCL], 2 mantle cell lymphoma, 1 Burkitt lymphoma, 5 peripheral T-cell lymphoma [PTCL], 15 follicular lymphoma [FL], 2 mucosa-associated lymphoid tissue, and 2 chronic lymphocytic leukemia/small lymphocytic lymphoma). The expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) was determined via immunohistochemistry in 17 postsurgical and 25 biopsy specimens, including 5 HL, 17 DLBCL, 1 mantle cell lymphoma, 1 Burkitt lymphoma, 4 PTCL, 12 FL, 1 mucosa-associated lymphoid tissue, and 1 chronic lymphocytic leukemia/small lymphocytic lymphoma.
Furthermore, tumor tissues were sliced into serial sections (4 μm) for immunohistochemical staining and analysis as previously described (10,12). Immunohistochemical staining was performed with primary antibodies including anti-FAP (1:400), anti-GLUT1 (1:200), and anti-HK2 (1:200) for 12 h at 4°C. Subsequently, horseradish peroxidase–labeled secondary antibodies (1:200) were incubated for 1 h and then mixed with 3,3-diaminobenzidine solution for 15 min at room temperature (22°C–26°C). Two experienced pathologists reviewed all the tissue sections. Finally, the expression of FAP, HK2, and GLUT1 was assessed visually and quantitatively according to the intensity and density of positive staining.
Statistical Analysis
All statistical analyses were performed using SPSS 20.0 software (IBM Corp.). The median and range of SUVs and TLRs are presented. Subsequently, the SUVmax and TLR of 68Ga-FAPI and 18F-FDG PET/CT were compared using the paired-samples t test (normally distributed variables) or the Wilcoxon signed-rank test (skewed variables). The correlation between FAP, HK2, and GLUT1 expression and 18F-FDG or 68Ga-FAPI uptake was evaluated using the Spearman rank correlation coefficient. A 2-tailed P value of less than 0.05 was considered statistically significant.
RESULTS
Participant Characteristics
Figure 1 shows the flowchart of participant enrollment, and Table 1 summarizes their characteristics. In total, 186 participants with various lymphoma subtypes (median age, 52 y [interquartile range, 41–64 y]; 95 women) were enrolled. PET/CT scans were performed on 133 newly diagnosed participants, 26 participants with progressive disease, and 27 participants experiencing relapse. Non-Hodgkin lymphoma (87.1% [162 of 186]) was the most prevalent pathologic subtype. Of the 186 participants, 56 (30.1%) had only lymph node involvement and 40 (21.5%) had primary extranodal lymphomas.
Flowchart of participant enrollment.
Participant Characteristics
Participant-Based Visual Analysis
The 68Ga-FAPI PET/CT and 18F-FDG PET/CT scans of all participants were evaluated. Lymphomas could be visually detected via 68Ga-FAPI PET/CT in 164 of 186 (88.2%) participants because of low background activity, whereas on 18F-FDG PET/CT, they were detected in 182 (97.8%) participants. When both imaging techniques were used, lymphomas were detected in all participants.
The dual-tracer imaging revealed 3 imaging patterns. Lesional accumulation was greater for 68Ga-FAPI than for 18F-FDG in 9 of 186 (4.8%) participants but was similar between the 2 tracers in 70 of 186 (37.6%) participants. However, in 57.5% (107 of 186) of participants, lesions were less avid for 68Ga-FAPI than for 18F-FDG. On a participant-based comparison according to the visual system, 18F-FDG PET/CT showed a higher accumulation than 68Ga-FAPI PET/CT for all lymphoma subtypes (Fig. 2). 68Ga‐FAPI PET/CT and 18F-FDG PET/CT identified 30 of 38 (78.9%) and 35 of 38 (92.1%) participants with bone marrow involvement, respectively. Three (7.9%) participants with bone marrow involvement were missed via dual-tracer PET/CT. 18F-FDG PET possessed a higher staging accuracy (98.4%) than 68Ga‐FAPI PET (86.0%) (Supplemental Table 1; supplemental materials are available at http://jnm.snmjournals.org).
Visual comparative system was developed to compare detection performance of 68Ga-FAPI PET/CT and 18F-FDG PET/CT for all lymphoma subtypes. B-NHL = B-cell non-Hodgkin lymphoma; NHL = non-Hodgkin lymphoma; T-NHL = T-cell non-Hodgkin lymphoma.
Lesion-Based Visual Analysis
In total, 5,980 lymphoma lesions (4,642 nodal and 1,338 extranodal) were detected. 68Ga-FAPI PET/CT identified 3,041 lesions (50.9%; 2,196 nodal and 845 extranodal), whereas 18F-FDG PET/CT located 5,928 (99.1%, 4,624 nodal and 1,304 extranodal) (Figs. 3 and 4). Additionally, 50% of lesions (2,989 of 5,980) were interpreted as double-positive (68Ga-FAPI–positive/18F-FDG–positive), whereas 0.9% of lesions (52 of 5,980) were 68Ga-FAPI–positive/18F-FDG–negative, including 18 nodal and 34 extranodal lesions. Furthermore, 49.1% of lesions (2,939 of 5,980) were 18F-FDG–positive but 68Ga-FAPI–negative, comprising 2,446 nodal and 493 extranodal lesions. The double-negative lesions (68Ga-FAPI–negative/18F-FDG–negative) were found only in bone marrow involvement cases, as confirmed via morphologic imaging and follow-up examination (Supplemental Table 2).
Images of 68Ga-FAPI and 18F-FDG PET/CT in 46-y-old woman with lymphoblastic leukemia/lymphoma. (A) Maximum-intensity projection of 68Ga-FAPI PET. (B–H) Axial 68Ga-FAPI PET/CT images (B, E, and G) and 18F-FDG PET/CT images (C, F, and H). (D) Maximum-intensity projection of 18F-FDG PET. Left breast involvement was detected with intense 68Ga-FAPI and 18F-FDG uptake (B and C, arrows). PET/CT image showed lesion with focal 68Ga-FAPI uptake in pancreas (E, arrow) and normal 18F-FDG activity (F, arrow). 18F-FDG PET/CT image showed lymph nodes positive for uptake in internal mammary and subpleural areas (H, arrows), without corresponding 68Ga-FAPI uptake (G, arrows). Intense 68Ga-FAPI uptake was noted in uterus (A, arrow).
Images of 68Ga-FAPI and 18F-FDG PET/CT in 60-y-old woman with DLBCL. (A) Maximum-intensity projection of 68Ga-FAPI PET. (B–H) Axial 68Ga-FAPI PET/CT images (B, E, and G) and 18F-FDG PET/CT images (C, F, and H). (D) Maximum-intensity projection of 18F-FDG PET. Hypermetabolic pulmonary nodule on 18F-FDG PET/CT did not indicate uptake of 68Ga-FAPI (B and C, arrows). 68Ga-FAPI PET/CT was superior to 18F-FDG PET/CT in depicting involvement of pancreas (E and F, arrows). Lymph node showed more intense uptake of 8F-FDG than of 68Ga-FAPI (G and H, arrows). 18F-FDG PET/CT identified 3 involved lymph nodes in left inguinal region, whereas 68Ga-FAPI PET/CT did not detect those lymph nodes (D, arrows). Intense 68Ga-FAPI uptake was noted in uterus (A, arrow).
Lesion-Based Semiquantitative Analysis
The SUVmax and TLR of lymphoma lesions detected via 68Ga-FAPI were compared with those detected via 18F-FDG PET/CT (Table 2). All tumor entities exhibited a higher interindividual and intralesional SUVmax variation on 68Ga-FAPI PET/CT than on 18F-FDG PET/CT. However, the highest uptake of 68Ga-FAPI did not significantly differ from that of 18F-FDG in most subtypes, except DLBCL, PTCL, extranodal NK/T-cell lymphoma, and FL (P < 0.05). Regarding TLR, nearly all lymphoma subtypes presented no relevant differences, except HL (P = 0.01).
Comparison of 68Ga-FAPI and 18F-FDG PET/CT Based on Tracer Uptake and TLR of Lesions
Table 3 lists the SUVmax obtained via 68Ga-FAPI and 18F-FDG PET/CT for comparing nodal and extranodal lesions by lymphoma subtype. In nodal lesions, the 68Ga-FAPI SUVmax and 18F-FDG SUVmax showed no significant difference for most lymphoma subtypes, except DLBCL (P < 0.001) and FL (P < 0.001). Similarly, in extranodal lesions, no significant difference was found between these values in most subtypes, except DLBCL (P < 0.001), PTCL (P = 0.03), and lymphoblastic leukemia/lymphoma (P = 0.04).
Comparison of 68Ga-FAPI and 18F-FDG Uptake in Nodal and Extranodal Lesions by Different Lymphoma Subtypes
In total, 141 of the 186 (75.8%) participants with lymphoma presented with extranodal involvement (Table 4). In comparing extranodal lesions according to organ involvement, we found that the median 18F-FDG SUVmax was significantly higher than the median 68Ga-FAPI SUVmax in the stomach, bone/bone marrow, intestine, muscle, nasal cavity, breast, and liver (P < 0.05).
Comparison of 68Ga-FAPI and 18F-FDG Uptake in Extranodal Regions of Lymphoma
Immunohistochemistry
Figure 5 shows representative examples of the FAP, HK2, and GLUT1 immunostaining results. Of 62 specimens, 40 (64.5%) stained positively for FAP: 55.6% (5/9) of HL, 80.8% (21/26) of DLBCL, 50% (1/2) of mantle cell lymphoma, 100% (1/1) of Burkitt lymphoma, 80% (4/5) of PTCL, 40% (6/15) of FL, 50% (1/2) of mucosa-associated lymphoid tissue, and 50% (1/2) of chronic lymphocytic leukemia/small lymphocytic lymphoma specimens. FAP was locally expressed in stromal cells and was observed predominantly on the plasma membrane (Fig. 5G).
Immunohistochemical staining of FAP, HK2, and GLUT1 (×200 for A–F and ×400 for G–I). (A, B, and C) DLBCL samples with intense, mild, and intense expression of FAP, HK2, and GLUT1, respectively. (D–F) No positive staining for FAP was observed in low-grade FL (D), whereas that for HK2 (E) and GLUT1 (F) was mild to moderate. (G) FAP (arrows) was detected only in stromal cells and was localized predominantly on plasma membrane. (H) HK2 (arrows) was specifically located in cytoplasm. (I) GLUT1 (arrows) was found on plasma membrane and in cytoplasm.
Of 42 specimens, 30 (71.4%) stained positively for HK2 and 32 (76.2%) for GLUT1. HK2 and GLUT1 were expressed in 80% (4 of 5) and 100% (5 of 5) of HL, 88.2% (15/17) and 82.4% (14/17) of DLBCL, 50% (2/4) and 75% (3/4) of PTCL, and 50% (6/12) and 66.7% (8/12) of FL specimens, respectively. Additionally, HK2 and GLUT1 were detected in both lymphoma cells and the TME. Specifically, HK2 was located in the cytoplasm (Fig. 5H) and GLUT1 on the cell membrane and in the cytoplasm (Fig. 5I).
The mean cell densities of FAP, HK2, and GLUT1 expression in lymphomas were 24.7%, 45.6%, and 58.0%, respectively (Fig. 6). For non-Hodgkin lymphoma, the SUVmax of lesions correlated significantly with the cell densities of FAP expression (r = 0.622, P = 0.001), consistent with the findings of a previous study (7). GLUT1 expression correlated positively with the SUVmax of the involved lesions (r = 0.835, P < 0.001); however, HK2 expression was not significantly associated with 18F-FDG uptake (r = 0.13, P = 0.49). Additionally, the cell densities of FAP expression were significantly lower than those of HK2 and GLUT1 expression in most lymphoma subtypes (P < 0.001), generating a weaker tracer uptake of 68Ga-FAPI than of 18F-FDG.
Cell densities of FAP, HK2, and GLUT1 in different lymphoma subtypes. FAP had significantly lower cell densities than HK2 and GLUT1 in most lymphoma subtypes. BL = Burkitt lymphoma; CLL/SLL = chronic lymphocytic leukemia/small lymphocytic lymphoma; MALT = mucosa-associated lymphoid tissue; MCL = mantle cell lymphoma.
DISCUSSION
To the best of our knowledge, this was the first study to comprehensively compare 68Ga-labeled FAPI PET/CT with 18F-labeled FDG PET/CT in terms of FAP expression and glycolytic metabolism in different histologic subtypes of lymphoma. Through dual-tracer imaging, 3 imaging patterns were revealed: 68Ga-FAPI PET/CT imaging profiles were inferior to (57.5%), similar to (37.6%), or superior to (4.8%) 18F-FDG PET/CT imaging profiles. Tracer avidities depend mainly on the origin, density, and distribution of FAP and glycolytic markers in the involved lesions (12,13). Glycolytic markers with high cell density were overexpressed in tumors and the TME, resulting in the higher rates of detecting lymphoma. Taken together, the findings indicate that the imaging modality of choice for the diagnosis of lymphoma should still be 18F-FDG PET/CT, which is also the current standard.
FAP-positive cancer-associated fibroblasts are reportedly related to the survival of participants with lymphomas and are potential new molecular targets (6). To support histopathologic and genic evidence, previous studies visualized FAP-expressing cancer-associated fibroblasts in most lymphoma subtypes via 68Ga-FAPI PET/CT and suggested that FAP is a suitable target for diagnostic and therapeutic regimens (7–9). To further characterize the role of 68Ga-FAPI PET/CT in lymphoma, we recruited more participants with lymphoma and conducted a head-to-head comparison with 18F-FDG PET/CT, which is the current standard, in the same participants with different lymphoma subtypes.
Compared with 18F-FDG PET/CT, 68Ga-FAPI PET/CT showed more intrasubtype, intraindividual, and intralesion variations in the avidity of lymphomas and seemed to be inferior, similar, or superior to 18F-FDG PET/CT in the participant-based visual analysis. We hypothesized that TME reprogramming induced by lymphoma cells, growth factors, cytokines, and other enzymes (14) can result in a varying FAP occurrence in the stromal cells of lymphoma, especially in the indolent subtypes. Our immunohistochemical analysis revealed FAP-positive expression in 55.6%, 80.8%, 80%, and 40% of participants with HL, DLBCL, PTCL, and FL, respectively. Furthermore, indolent lymphomas contained low-cell-density FAP. These results may explain the lower 68Ga-FAPI SUVmax in some lesions or subtypes. Additionally, the FAP expression of nodal lesions correlated with nodal size. Serfling et al. (15) reported that lymph nodes up to 7 mm in size exhibited weak FAP expression in less than 10% of the surrounding tumor-associated stromal cells. This finding might explain the FAPI-negative expression in small nodes and lower nodal detection rates in 68Ga-FAPI PET/CT.
The Warburg effect represents the metabolic reprogramming of cancer cells to favor glycolytic metabolism (16). Recently, aerobic glycolysis has been increasingly proven to be a key process in brisk immune infiltrates and tertiary lymphoid structures in the TME (17). Our immunohistochemical data proved that HK2 and GLUT1 are highly expressed in both tumor cells and the TME. Additionally, the positive rates (71.4% and 76.2% vs. 64.5%) and cell densities (45.6% and 58.0% vs. 24.7%) of HK2 and GLUT1 were higher than those of FAP in lymphoma specimens. These results might explain why 18F-FDG PET/CT possessed a superior imaging profile in most of the participants and could detect more lesions, especially the nodal lesions. Histopathologically, the 18F-FDG SUVmax was significantly higher than the 68Ga-FAPI SUVmax in DLBCL, PTCL, extranodal NK/T-cell lymphoma, and FL. Extranodal organs (including bone marrow), which were mostly involved in DLBCL, accumulated more 18F-FDG than 68Ga-FAPI, although FAP was overexpressed by cancer-associated fibroblasts in the lymphoma stroma. Because of low background activity, TLR was not significant in nearly any lymphoma subtypes, except HL (P = 0.01). However, some lesions with larger diameters may still be missed during 18F-FDG PET/CT, which may reveal lower expression of HK2 and GLUT1 in tumor cells (18).
Moreover, the dual-tracer imaging was promising. It not only located all lymphoma lesions but also allowed whole-body lymphoma characterization. Evaluating tumor intraparticipant and interlesion heterogeneity might elucidate the interaction occurring in lymphoma progression and set the basis for new cancer-monitoring strategies.
This study had some limitations. First, histopathologic results were not available for all lymphoma subtypes because not all imaging-positive lesions were biopsied. Second, the number of participants with rare lymphoma subtypes was relatively small, resulting in statistical uncertainty. Third, prognostic implications were not addressed.
CONCLUSION
68Ga-labeled FAPI PET/CT was inferior to 18F-labeled FDG PET/CT in diagnosing lymphoma. However, 68Ga-FAPI PET/CT could characterize the cancer-associated fibroblast status, which might be helpful in analyzing the long-term prognosis of patients with respect to their disease-free and overall survival.
DISCLOSURE
This study was financially supported by the National Natural Science Foundation of China (82071957), the Capital’s Funds for Health Improvement and Research (2018-2-1024), the Beijing Hospitals Authority Clinical Medicine Development special funding support (XMLX202120), and the Beijing Hope Run Special Fund of the Cancer Foundation of China (LC2022L04). No other potential conflict of interest relevant to this article was reported.
KEY POINTS
QUESTION: Can 68Ga-FAPI PET/CT be an alternative method to 18F-FDG PET/CT for characterizing lymphoma profiles?
PERTINENT FINDINGS: 68Ga-FAPI PET/CT showed lower rates of detecting lymphomas than 18F-FDG PET/CT (50.9% vs. 99.1%). FAP and GLUT1 expression correlated positively with radiotracer accumulation in lymphoma lesions (68Ga-FAPI: r = 0.622, P = 0.001; 18F-FDG: r = 0.835, P < 0.001).
IMPLICATIONS FOR PATIENT CARE: 68Ga-FAPI PET/CT (whose performance was associated with FAP expression) was inferior to 18F-FDG PET/CT in detecting lymphomas that overexpressed glycolytic markers. High 68Ga-FAPI uptake in aggressive lymphoma, including HL, implied the potential for application of FAP-targeted radionuclide therapy.
Footnotes
Published online Jun. 29, 2023.
- © 2023 by the Society of Nuclear Medicine and Molecular Imaging.
REFERENCES
- Received for publication January 30, 2023.
- Revision received April 20, 2023.
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