Visual Abstract
Abstract
18F-labeled somatostatin analogs (SSAs) could represent a valid alternative to the current gold standard, 68Ga-labeled SSAs, for somatostatin receptor imaging in patients with neuroendocrine tumors (NETs), given their logistic advantages. Recently, 18F-AlF-NOTA-octreotide (18F-AlF-OC) has emerged as a promising candidate, but a thorough comparison with 68Ga-DOTA-SSA in large patient groups is needed. This prospective, multicenter trial aims to demonstrate noninferiority of 18F-AlF-OC compared with 68Ga-DOTA-SSA PET in NET patients (ClinicalTrials.gov, NCT04552847). Methods: Seventy-five patients with histologically confirmed NET and routine clinical 68Ga-DOTATATE (n = 56) or 68Ga-DOTANOC (n = 19) PET, performed within a 3-mo interval of the study scan (median, 7 d; range, −30 to +32 d), were included. Patients underwent a whole-body PET 2 h after intravenous injection of 4 MBq/kg of 18F-AlF-OC. A randomized, masked consensus read was performed by 2 experienced readers to count tumor lesions. After unmasking, the detection ratio (DR) was determined for each scan, that is, the fraction of lesions detected on a scan compared with the union of lesions of both scans. The differential DR (DDR; difference in DR between 18F-AlF-OC and 68Ga-DOTATATE/NOC) per patient was calculated. Tracer uptake was evaluated by comparing SUVmax and tumor-to-background ratios in concordant lesions. Results: In total, 4,709 different tumor lesions were detected: 3,454 with 68Ga-DOTATATE/NOC and 4,278 with 18F-AlF-OC. The mean DR with 18F-AlF-OC was significantly higher than with 68Ga-DOTATATE/NOC (91.1% vs. 75.3%; P < 10−5). The resulting mean DDR was 15.8%, with a lower margin of the 95% CI (95% CI, 9.6%–22.0%) higher than −15%, which is the prespecified boundary for noninferiority. The mean DDRs for the 68Ga-DOTATATE and 68Ga-DOTANOC subgroups were 11.8% (95% CI, 4.3–19.3) and 27.5% (95% CI, 17.8–37.1), respectively. The mean DDR for most organs was higher than zero, except for bone lesions (mean DDR, −2.8%; 95% CI, −17.8 to 12.2). No significant differences in mean SUVmax were observed (P = 0.067), but mean tumor-to-background ratio was significantly higher with 18F-AlF-OC than with 68Ga-DOTATATE/NOC (31.7 ± 36.5 vs. 25.1 ± 32.7; P = 0.001). Conclusion: 18F-AlF-OC is noninferior and even superior to 68Ga-DOTATATE/NOC PET in NET patients. This validates 18F-AlF-OC as an option for clinical practice somatostatin receptor PET.
Neuroendocrine tumors (NETs) are part of a heterogeneous group of relatively rare tumors that develop from cells of the diffuse neuroendocrine system and are mainly found in the gastrointestinal and respiratory tracts. Many NETs show an overexpression of the somatostatin receptor (SSTR), a G-protein–coupled membrane receptor that makes an excellent target for molecular imaging and therapy with radiolabeled somatostatin analogs (SSAs) (1). SSTR imaging plays a crucial role in the diagnostic work-up, treatment selection, follow-up, and recurrence detection of NETs (1). 68Ga-DOTATATE, 68Ga-DOTATOC, and 68Ga-DOTANOC, which can be collectively referred to as 68Ga-DOTA-SSAs, are considered as the current gold standard for SSTR imaging (1,2). However, their widespread clinical implementation faces challenges inherent to the use of 68Ge/68Ga generators, such as limited availability, high associated costs, and low activity yield per elution (3). These challenges can be largely overcome by an 18F-labeled alternative. In particular, the high activity yield in combination with a favorable half-life of 109.8 min enables centralized production of 18F-labeled tracers followed by distribution to distant PET centers without cyclotron access (3). Furthermore, 18F has a shorter positron range than 68Ga and is therefore more suitable for high-spatial-resolution imaging on modern PET cameras (3).
Recently, 18F-AlF-NOTA-octreotide (18F-AlF-OC) has emerged as a promising 18F-labeled SSA for SSTR imaging (4,5). 18F-AlF-OC is synthetized using the chelator-based Al18F-method (6). To allow clinical implementation, a fast and robust automated good-manufacturing-practice–compliant process was recently developed (7). Two independently performed first clinical translations of 18F-AlF-OC in healthy volunteers and NET patients have reported favorable dosimetry, biodistribution, tracer kinetics, and lesion targeting (4,5). First comparisons of 18F-AlF-OC with 68Ga-DOTATATE in 2 small NET patient groups (n = 6 and n = 20) have shown similar lesion detection rates and tumor uptake (5,8). However, a thorough head-to-head comparison with 68Ga-DOTA-SSA PET in large patient groups is still lacking.
This prospective multicenter trial aimed to demonstrate that the diagnostic performance of 18F-AlF-OC PET is equivalent or superior to the current gold standard, 68Ga-DOTA-SSA PET, in NET patients (noninferiority trial).
MATERIALS AND METHODS
A full version of the Materials and Methods section is provided in the supplemental information (supplemental materials are available at http://jnm.snmjournals.org).
Study Population
In the main part (part A) of this prospective multicenter trial, 75 NET patients, 18 y of age or older, were included. The main inclusion criteria were as follows: histologically or cytologically confirmed NET of all grades of gastroenteropancreatic, pulmonary, neural crest, or unknown primary origin; routine clinical 68Ga-DOTA-SSA PET/CT scheduled within 3 mo before or after the study scan; and at least 1 known tumor lesion below the level of the submandibular and parotid glands, with either a minimum size of 1 cm in at least 1 dimension on morphologic imaging (CT, MRI, or ultrasound) or an SUVmax of at least 10 on 68Ga-DOTA-SSA PET. The main exclusion criterion was previous or ongoing recurrent or chronic disease at high risk to interfere with the performance or evaluation of the trial. The PET/MRI part (part B) of the trial in 10 NET patients will be presented elsewhere.
The study was performed at University Hospitals Leuven in collaboration with University Hospital Antwerp and University Hospital Ghent after approval by the Ethics Committee of all 3 institutes, and all subjects gave written informed consent (ClinicalTrials.gov identifier, NCT04552847; EudraCT, 2020-000549-15).
PET/CT Acquisition
We previously identified 2 h after injection to be the optimal time point for imaging (5). Patients underwent whole-body PET (from mid thigh to vertex) 2 h after intravenous injection of 4 MBq/kg of 18F-AlF-OC, preceded by a low-dose CT scan for attenuation correction and anatomic information.
For both the routine and study scans, patients were asked to avoid long-acting SSA treatment, except in cases of uncontrolled hormonal symptoms, for 4–6 wk before the scan.
Image Analyses
All image analyses were done using MIM, version 7.1.5 (MIM Software Inc.). Tumor lesions were counted in consensus by 2 experienced readers, and the patient data and radiopharmaceutical that was used were masked from the reader. Routine and study scans were randomized per group of 20 patients (40 scans per group), and information regarding patient and radiopharmaceutical was removed from the Digital Imaging and Communications in Medicine headers. Furthermore, since normal salivary gland uptake is markedly higher with 68Ga-DOTATATE than with 18F-AlF-OC (5,8), all PET datasets were trimmed by an independent operator to remove the head region. A positive lesion was defined as a volume of increased tracer uptake, compared with background, that was deemed to be caused by the presence of NET cells and was unlikely to be attributed to a physiologic or benign etiology (e.g., inflammation, blood pool retention, or excretion). A detailed description of the consensus read is provided in the supplemental information.
After unmasking, the detection ratio (DR) was determined for each scan, that is, the fraction of lesions detected on that scan, using the union of lesions detected by both tracers (68Ga-DOTATATE/NOC and 18F-AlF-OC) in a patient as the reference. Finally, the differential DR (DDR), which is the difference in DR between 18F-AlF-OC and 68Ga-DOTATATE/NOC, was calculated for each patient. The DR at organ level was determined as the number of lesions detected with 1 tracer divided by all lesions detected by both tracers in a specific organ.
For each lesion, the SUVmax was measured, and the tumor-to-background ratio (TBR) was calculated by dividing the SUVmax of that lesion by the SUVmean of relevant background tissue (liver for liver lesions, bone for bone lesions, and gluteal muscle for all other lesions). In patients for whom no healthy liver (n = 1) or bone tissue (n = 2) could be delineated, the mean background value of all other patients was used instead to determine TBRs. Lesions with incorrect attenuation correction because of PET/CT misregistration were excluded from semiquantitative analysis.
Outcomes
The primary outcome measure was the DDR. The primary objective, that is, noninferiority of 18F-AlF-OC compared with 68Ga-DOTATATE/NOC, would be met if the lower margin of the 95% CI for the mean DDR was higher than −15%.
Secondary outcome measures included the following: lesion uptake in matched pairs of lesions (SUVmax and TBR), DR and DDR at organ level, DDR in function of the specific 68Ga-DOTA-SSA used (68Ga-DOTATATE or 68Ga-DOTANOC) and tumor grade, and impact of 18F-AlF-OC administration on blood pressure and heart rate. A post hoc analysis according to primary tumor site (for n > 10) was performed as well.
Lesion uptake was assessed, first, at the patient level; second, for 2 subsets of hottest lesions (i.e., 20 lesions per patient and a maximum of 5 lesions per organ, at the patient level); and third, at the lesion level. For secondary outcome measures, tumor lesions in the head region, identified through a nonmasked consensus read, were added in the analyses. The safety evaluation is provided in the supplemental information.
RESULTS
Patients and 18F-AlF-OC Administration
Patient and clinical characteristics are shown in Table 1. The median time between the 18F-AlF-OC and routine 68Ga-DOTATATE/NOC scan was 7 d (range, −30 to 32 d), with 52 patients (78.7%) having both scans within a 15-d interval (Supplemental Fig. 1). No therapeutic changes occurred between the scans, except in 3 patients: in 1 patient, everolimus was added 2 d before the second scan (18F-AlF-OC); in 1 patient, everolimus was added 7 d before the second scan (18F-AlF-OC); and in 1 patient, SSA treatment was reinitiated 13 d before the second scan (18F-AlF-OC). The mean injected activity and peptide mass of 18F-AlF-OC were 295 ± 60 MBq and 11.2 ± 6.8 μg, respectively.
Patient and Clinical Characteristics (n = 75)
Detection Rate Analysis
During the masked consensus read, 4,709 different tumor lesions were counted: 3,454 with 68Ga-DOTATATE/NOC and 4,278 with 18F-AlF-OC. In 48 patients, 18F-AlF-OC detected more lesions than 68Ga-DOTATATE/NOC, whereas 68Ga-DOTATATE/NOC detected more lesions in only 15 patients. The mean DR with 18F-AlF-OC was significantly higher than with 68Ga-DOTATATE/NOC (91.1% vs. 75.3%; P < 10−5). The resulting mean DDR was 15.8% (95% CI, 9.6%–22.0%). As the lower margin of the 95% CI was higher than −15%, the primary objective of the trial was met. DDRs ranged from −74.2% to 77.5% (interquartile range, 0.0%–32.7%; Supplemental Fig. 2).
In the head region, 214 additional lesions were counted. A summary of results for the most relevant organs is provided in Table 2. A full analysis at the organ level is shown in Supplemental Table 1. Organs where most lesions were observed were bone (2,012 lesions in 50 patients), followed by liver (1,739 lesions in 54 patients), lymph nodes (602 lesions in 63 patients), peritoneum (275 lesions in 28 patients), and lung (195 lesions in 18 patients). The mean DR for these sites was significantly higher with 18F-AlF-OC than with 68Ga-DOTATATE/NOC, with mean DDRs well above zero, except for bone, where the DR with both tracers was similar (79.8% vs. 77.0%; mean DDR, −2.8%; 95% CI, −17.8 to 12.2).
Comparison Between Mean DR with 68Ga-DOTATATE/NOC (DRGa) and 18F-AlF-OC (DRF) and Mean DDR with 95% CI for Most Relevant Organs
Both within the 68Ga-DOTATATE and within the 68Ga-DOTANOC subgroups, the mean DR with 18F-AlF-OC was significantly higher than with 68Ga-DOTATATE/NOC (Table 3). The mean DDR for the 68Ga-DOTATATE subgroup was 11.8% (95% CI, 4.3–19.3) versus 27.5% (95% CI, 17.8–37.1) for the 68Ga-DOTANOC subgroup. The detailed analysis is shown in Supplemental Tables 2 and 3.
Comparison Between Mean DR with 68Ga-DOTATATE/NOC (DRGa) and 18F-AlF-OC (DRF) and Mean DDR with 95% CI for Different Subgroups of Patients According to Routine 68Ga-DOTA-SSA Tracer, Tumor Grade, and Primary Tumor Site
Subgroup analysis according to tumor grade showed a similar mean DDR for grade 1 and grade 2 tumors (14.9% [95% CI, 6.0–23.8] vs. 16.6 [95% CI, 6.3–27.0], respectively; Table 3). The mean DDR for the grade 3 subgroup was 35.4%. However, because this group contained only 2 patients, no statistics could be applied. No significant correlation was observed between Ki-67 proliferation index and DDR (Spearman correlation coefficient [ρ] = 0.075, P = 0.54; Supplemental Fig. 3).
Finally, the mean DR for patients with a NET from intestinal origin was significantly higher with 18F-AlF-OC than with 68Ga-DOTATATE/NOC (mean DDR, 17.8%; 95% CI, 9.2–26.4), whereas no significant differences were observed for patients with a pancreatic NET (Table 3).
The forest plot in Figure 1 summarizes the results of the DR analysis. Head-to-head comparisons with examples of missed lesions are shown in Figures 2 and 3.
Forest plot summarizing mean DDR and 95% CI overall and for different subgroups of lesions and patients. Dashed vertical line represents prespecified boundary (−15%) for noninferiority for lower margin of 95% CI. G1 = grade 1; G2 = grade 2.
68Ga-DOTATATE (A) and 18F-AlF-OC (B) images (from top to bottom: maximum-intensity projection PET, transversal PET, and fused PET/CT images) of 64-y-old male patient with pancreatic NET and liver, lymph node, and peritoneal metastases. Multiple lesions in all 3 sites were missed by 68Ga-DOTATATE. Arrows indicate missed liver lesions. Lookup tables apply to PET images (SUV). Intensity scale bars indicate SUVs.
68Ga-DOTATATE (A) and 18F-AlF-OC (B) images (from top to bottom: maximum-intensity projection PET, transversal PET, and fused PET/CT images) of 74-y-old female patient with intestinal NET and bone, liver, lymph node, and peritoneal metastases. Multiple lesions in all 3 sites were missed by 18F-AlF-OC. Blue and green arrows indicate missed bone and lymph node lesions, respectively. Lookup tables apply to PET images (SUV). Intensity scale bars indicate SUVs.
Lesion Uptake
Mean SUVmax at the patient level showed a trend toward lower values with 18F-AlF-OC than with 68Ga-DOTATATE/NOC, but this was not statistically significant (20.0 vs. 22.4; P = 0.067). Conversely, TBR was significantly higher with 18F-AlF-OC (31.7 vs. 25.1; P = 0.001; Table 4; Fig. 4). Of note, background uptake was significantly lower with 18F-AlF-OC than with 68Ga-DOTATATE/NOC (4.2 ± 1.7 vs. 6.3 ± 2.5 [P < 10−7], 0.7 ± 0.2 vs. 1.2 ± 0.5 [P < 10−7], and 0.4 ± 0.1 vs. 0.6 ± 0.2 [P < 10−7]) for healthy liver, bone, and muscle, respectively; Supplemental Table 4). At the lesion level, SUVmax was significantly lower and TBR was significantly higher with 18F-AlF-OC than with 68Ga-DOTATATE/NOC (mean difference, −2.21 [95% CI, −4.28 to −0.15; P = 0.036] and 8.47 [95% CI, 3.46–13.49; P = 0.001] for SUVmax and TBR, respectively). Similar results were observed for a subset of a maximum of the 20 hottest lesions per patient and 5 hottest lesions per organ (Table 4). Of note, considerable variation in lesion uptake was also observed within the same patient, with a higher SUVmax with 18F-AlF-OC in some lesions and a higher SUVmax with 68Ga-DOTATATE/NOC in others. Lesion uptake (at the patient level) per organ is shown in Table 4 and Supplemental Table 5. For the 3 most common metastatic sites (liver, bone, and lymph nodes), TBR was significantly higher with 18F-AlF-OC than with 68Ga-DOTATATE/NOC. However, only bone lesions showed a significantly lower SUVmax with 18F-AlF-OC. Lesion uptake at the patient level for patient subgroups according to routine 68Ga-DOTA-SSA tracer, tumor grade, and primary is summarized in Table 5 and (per organ analysis) Supplemental Table 6. Most strikingly, mean SUVmax with 68Ga-DOTANOC was significantly lower than with 18F-AlF-OC overall and also for liver, lymph node, and peritoneal lesions. Other subgroup results were in line with results for the whole patient group.
68Ga-DOTATATE/NOC Mean SUVmax (SUVmax_Ga) and TBR (TBRGa) and 18F-AlF-OC Mean SUVmax (SUVmax_F) and TBR (TBRF) at Patient Level for All Concordant, Quantifiable Lesions (n = 3,034) and Different Subsets of Lesions
Mean SUVmax (A) and TBR (B) at patient level with 18F-AlF-OC as function of mean SUVmax and TBR with 68Ga-DOTATATE/NOC. Gray line represents unity line.
68Ga-DOTATATE/NOC Mean SUVmax (SUVmax_Ga) and TBR (TBRGa) and 18F-AlF-OC Mean SUVmax (SUVmax_F) and TBR (TBRF) at Patient Level for Different Subgroups of Patients According to Routine 68Ga-DOTA-SSA Tracer, Tumor Grade, and Primary
The Bland–Altman plot showed fair agreement between mean SUVmax with 18F-AlF-OC and 68Ga-DOTATATE/NOC, with a bias toward an increased SUVmax in the 68Ga-DOTATATE subgroup and a decreased SUVmax in the 68Ga-DOTANOC subgroup compared with 18F-AlF-OC (Supplemental Fig. 4).
DISCUSSION
This prospective trial aimed to demonstrate noninferiority of 18F-AlF-OC compared with 68Ga-DOTA-SSA PET in NET patients. The objective would be met if the lower margin of the 95% CI for the mean DDR were higher than −15%. We observed a mean DDR of 15.8% (95% CI, 9.6%–22.0%), demonstrating superiority of 18F-AlF-OC compared with 68Ga-DOTATATE/NOC. Per-organ analysis showed that 18F-AlF-OC outperforms 68Ga-DOTATATE/NOC, with DRs of around 90% or higher for most sites and with bone being the most important exception. Overall, lesions missed by 18F-AlF-OC were mainly situated in bone, in line with our previous findings (5). Nevertheless, the diagnostic performance for bone lesions of 18F-AlF-OC was similar to that of 68Ga-DOTATATE/NOC (DR, ∼80%; mean DDR, −2.8%). Results for the 68Ga-DOTATATE and 68Ga-DOTANOC subgroups were more or less in line with the results for the total patient group, except for bone lesions, for which 68Ga-DOTATATE showed a significantly higher DR than did 18F-AlF-OC whereas 68Ga-DOTANOC had a significantly lower DR. The DDR was higher in the 68Ga-DOTANOC subgroup than in the 68Ga-DOTATATE subgroup, implying that 18F-AlF-OC outperforms 68Ga-DOTANOC even more than 68Ga-DOTATATE. The grade 1 and grade 2 subgroups had a similar DDR (insufficient data for grade 3 tumors), and no associations between the Ki-67 proliferation index and DDR were observed. The DR analysis for patients with a NET from intestinal origin was similar to that for the whole patient cohort, whereas for patients with a pancreatic NET, 18F-AlF-OC and 68Ga-DOTATATE/NOC performed equally well.
Lesion uptake in terms of TBR, which is the most important parameter for lesion detectability, was significantly higher for 18F-AlF-OC than for 68Ga-DOTATATE/NOC, both at the patient level and at the lesion level, as well as for most organs, including bone. This is reflected in the overall higher DRs for 18F-AlF-OC. Conversely, in comparison with SUVmax with 68Ga-DOTATATE/NOC, SUVmax with 18F-AlF-OC was either significantly lower (e.g., at the lesion level, for subsets of hottest lesions per patient and for bone lesions) or similar (e.g., at the patient level and for most organs). These results are in line with our previous findings (5) but slightly differ from those of Hou et al. (8) because they observed not only higher TBRs but also a higher SUVmax with 18F-AlF-OC than with 68Ga-DOTATATE, although the latter was not statistically significant. Nevertheless, higher TBRs for 18F-AlF-OC are mainly explained by significantly lower background uptake. In particular, the lower background uptake with 18F-AlF-OC in the liver significantly improves detection of liver metastases as reflected by the high DDR of 33.1% (95% CI, 21.7%–44.4%), which is consistent with previous observations (5,8). Tracer clearance may partly explain the lower background values for 18F-AlF-OC, as 18F-AlF-OC imaging was done at a later time point (2 h after injection) than was 68Ga-DOTATATE (45–60 min after injection) or 68Ga-DOTANOC (45–60 min after injection) imaging. However, Hou et al. (8) also reported a 1.5 times lower liver background with 18F-AlF-OC at 60 min after injection than with 68Ga-DOTATATE at 50 min after injection, as well as significantly lower bone background.
Lesion uptake for the 68Ga-DOTATATE subgroup was similar to that for the whole patient cohort. Conversely, in the 68Ga-DOTANOC subgroup the mean SUVmax was significantly lower with 68Ga-DOTANOC than with 18F-AlF-OC, in line with findings from a head-to-head comparison between 68Ga-DOTANOC and 68Ga-DOTATATE, where a significantly lower lesion SUVmax was reported with 68Ga-DOTANOC (9). This can most likely be explained by differences in the SSTR affinity profile, because 68Ga-DOTATATE has an almost 10-fold higher affinity for SSTR2, which is the SSTR subtype that is most frequently expressed in NETs, than does 68Ga-DOTANOC (9–11).
In accordance with Hou et al. (8), we observed considerable variability in lesion uptake both between and within patients. Differences in SSTR affinity profile between 18F-AlF-OC and 68Ga-DOTATATE/NOC (to our knowledge, the exact affinity profile for 18F-AlF-OC is still unknown) in combination with NET heterogeneity may lie at the basis of this finding. Of note, this variability has also been reported in a head-to-head comparison between 68Ga-DOTATATE and 68Ga-DOTATOC (12). In particular, the Bland–Altman plot of mean differences in mean SUVmax with 68Ga-DOTATATE and 68Ga-DOTATOC showed a similar range between the limits of agreement, as we observed for mean SUVmax with 18F-AlF-OC and 68Ga-DOTATATE (12). As 68Ga-DOTATATE and 68Ga-DOTATOC are considered equivalent in clinical practice, we believe that the uptake variability for 18F-AlF-OC will also be of limited relevance for implementation in routine practice. Furthermore, especially in cases of disseminated disease, it is likely that 18F-AlF-OC and 68Ga-DOTATATE/NOC could be used interchangeably without clinical impact. A population that might benefit from 18F-AlF-OC is patients with confined liver disease in whom liver-directed therapies are considered.
The most important limitation of this trial is the lack of histologic confirmation of all detected lesions; such confirmation was not possible for ethical and practical reasons. Therefore, we did not have a perfect reference for evaluation of diagnostic performance because some lesions may have been false-positive. However, false-positive lesions are considered rare, because in most cases, additional lesions with 1 tracer compared with the other were observed in organs already known to be metastatically involved. Furthermore, in some cases, additional lesions observed with 18F-AlF-OC in previously unknown disease sites were later confirmed on 68Ga-DOTATATE/NOC follow-up imaging (Supplemental Fig. 5). Second, for practical reasons, it was not possible to organize the study scan within a day of the routine scan. Although the interval between scans was kept to a minimum, in about 20% of patients the interval was more than 15 d (≤32 d). However, as most patients had stable disease, especially those with a longer time between scans, the influence of the scan interval on the results of the trial is deemed negligible. Third, the time between long-acting SSA intake and the scan was not standardized. However, a recent prospective study reported no significant changes in tumor uptake depending on the time since last SSA intake (13). Fourth, in 3 patients, a therapeutic change occurred between the 2 scans. Because the same number of, or more, lesions were observed on the second scan, this will have no significant impact on the results of the study.
Finally, it is important to note the differences in imaging parameters, for example, the increased administered activity and time between tracer administration and imaging with 18F-AlF-OC compared with 68Ga-DOTATATE/NOC, because these most likely benefit the diagnostic performance of 18F-AlF-OC. However, these are examples of the advantages of 18F-labeled tracers over 68Ga-labeled tracers that should be exploited, because the ultimate aim is to provide an alternative tracer for clinical practice with beneficial manufacturing properties and increased cost-effectiveness compared with the current gold standard. Of note, the effective dose per injected activity is similar for 18F-AlF-OC and 68Ga-DOTA-SSAs (22.4 vs. 21 μSv/MBq, respectively) (3,5). Future trials may focus on identifying the optimal activity in combination with PET acquisition time for 18F-AlF-OC.
CONCLUSION
18F-AlF-OC demonstrated an excellent diagnostic performance, meeting our prespecified criterion for noninferiority, and showed superiority compared with 68Ga-DOTATATE/NOC in NET patients. This validates 18F-AlF-OC as an option for clinical practice SSTR PET.
DISCLOSURE
This research was funded by the project from Kom op tegen Kanker: “PET/MRI of the Norepinephrine Transporter and Somatostatin Receptor in Neural Crest and Neuroendocrine Tumors for Better Radionuclide Therapy Selection.” Christophe M. Deroose is a senior clinical investigator at Research Foundation-Flanders (FWO). No other potential conflict of interest relevant to this article was reported.
KEY POINTS
QUESTION: Is the diagnostic performance of 18F-AlF-OC PET equivalent or superior to the current gold standard, 68Ga-DOTA-SSA PET, in NET patients?
PERTINENT FINDINGS: In this prospective, multicenter study in 75 NET patients, a randomized, masked consensus read was performed to count tumor lesions on 18F-AlF-OC and 68Ga-DOTATATE/NOC PET/CT scans of each patient. The mean DDR between 18F-AlF-OC and 68Ga-DOTATATE/NOC was 15.8% (95% CI, 9.6%–22.0%), meeting the primary noninferiority objective of the trial and even demonstrating superiority of 18F-AlF-OC PET.
IMPLICATIONS FOR PATIENT CARE: 18F-AlF-OC is a validated alternative for clinical practice SSTR PET. These results could facilitate widespread implementation of this tracer and increase accessibility for patients.
ACKNOWLEDGMENTS
We thank Prof. Kristof Baete, Wies Deckers, and Stijn De Schepper of the medical physics team of UZ Leuven and UZ Antwerp; Kwinten Porters and Jef Van Loock; and the PET radiopharmacy team of UZ Leuven for their skilled contributions.
Footnotes
Published online Oct. 20, 2022.
- © 2023 by the Society of Nuclear Medicine and Molecular Imaging.
REFERENCES
- Received for publication June 23, 2022.
- Revision received October 4, 2022.
In this issue
Jump to section
Related Articles
Cited By...
- Somatostatin Receptor Imaging with [18F]FET-{beta}AG-TOCA PET/CT and [68Ga]Ga-DOTA-Peptide PET/CT in Patients with Neuroendocrine Tumors: A Prospective, Phase 2 Comparative Study
- 18F-Labeled Somatostatin Analogs as PET Tracers for the Somatostatin Receptor: Ready for Clinical Use
- 18F-Labeled Somatostatin Analogs as PET Tracers for the Somatostatin Receptor: Ready for Clinical Use