Research ArticleTheranostics

64Cu-DOTATATE PET in Patients with Neuroendocrine Neoplasms: Prospective, Head-to-Head Comparison of Imaging at 1 Hour and 3 Hours After Injection

Mathias Loft, Esben A. Carlsen, Camilla B. Johnbeck, Helle H. Johannesen, Tina Binderup, Andreas Pfeifer, Jann Mortensen, Peter Oturai, Annika Loft, Anne K. Berthelsen, Seppo W. Langer, Ulrich Knigge and Andreas Kjaer
Journal of Nuclear Medicine January 2021, 62 (1) 73-80; DOI: https://doi.org/10.2967/jnumed.120.244509

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Representative examples of liver lesions (A), bone lesions (B), lymph node lesions (C), and pancreatic lesions (D) in same patients scanned at 1 and 3 h after injection. From left to right are shown CT, 64Cu-DOTATATE PET, 64Cu-DOTATATE PET/CT, and maximum-intensity projection, with corresponding SUV color bars below. All lesions were identified at both 1 h and 3 h on 64Cu-DOTATATE PET (arrows). Ant = anterior; F = feet; H = head; p.i. = after injection; post = posterior.

  • FIGURE 2.
    FIGURE 2.

    True-positive finding in patient 1: one additional lymph node lesion (arrows) visible on 64Cu-DOTATATE PET at 3 h after injection but not at 1 h, with visible CT correlate. Lesion was also visible on PET and CT at 1 h after injection on 64Cu-DOTATATE PET/CT performed 9 mo later. From left to right are shown CT, 64Cu-DOTATATE PET, 64Cu-DOTATATE PET/CT, and maximum-intensity projection, with corresponding SUV color bars below. Ant = anterior; F = feet; H = head; p.i. = after injection; post = posterior.

  • FIGURE 3.
    FIGURE 3.

    True-positive finding in patient 4: one additional bone lesion (arrows) visible on 64Cu-DOTATATE PET at 3 h after injection but not at 1 h, with visible CT correlate. No later SSTR PET images were available. From left to right are shown CT, 64Cu-DOTATATE PET, 64Cu-DOTATATE PET/CT, and maximum-intensity projection, with corresponding SUV color bars below. Ant = anterior; F = feet; H = head; p.i. = after injection; post = posterior.

  • FIGURE 4.
    FIGURE 4.

    True-positive finding in patient 3: one additional liver lesion (arrows) visible on 64Cu-DOTATATE PET at 3 h after injection but not at 1 h, without CT correlate. This discordant lesion was also visible on PET and CT at 1 h after injection on 68Ga-DOTATOC PET performed 46 mo later. From left to right are shown CT, 64Cu-DOTATATE PET (68Ga-DOTATOC PET), 64Cu-DOTATATE PET/CT (68Ga-DOTATOC PET/CT), and maximum-intensity projection, with corresponding SUV color bars below. Ant = anterior; F = feet; H = head; p.i. = after injection; post = posterior.

  • FIGURE 5.
    FIGURE 5.

    True-positive finding in patient 5: one additional liver lesion (arrows) visible on 64Cu-DOTATATE PET at 3 h after injection but not at 1 h, with no visible CT correlate. This discordant lesion was also visible on PET without CT correlate at 1 h after injection on 68Ga-DOTATOC PET/CT performed 39 mo later. From left to right are shown CT, 64Cu-DOTATATE PET (68Ga-DOTATOC PET), 64Cu-DOTATATE PET/CT(68Ga-DOTATOC PET/CT), and maximum-intensity projection, with corresponding SUV color bars below. Ant = anterior; F = feet; H = head; p.i. = after injection; post = posterior.

  • FIGURE 6.
    FIGURE 6.

    False-positive finding in patient 2: one additional bone lesion (arrow) visible on 64Cu-DOTATATE PET at 1 h after injection but not at 3 h, without CT correlate. No later SSTR PET images were available. No visible CT correlate was seen on latest CT scan, 8 mo later (not shown). From left to right are shown CT, 64Cu-DOTATATE PET, 64Cu-DOTATATE PET/CT, and maximum-intensity projection, with corresponding SUV color bars below. Ant = anterior; F = feet; H = head; p.i. = after injection; post = posterior.

Tables

  • TABLE 1

    Patient Characteristics

    CharacteristicData
    Sex
     Male21 (60%)
     Female14 (40%)
    Age (y)
     Mean62
     Range40–81
    Site of primary tumor
     Lung3 (9%)
     Gastrointestinal13 (37%)
     Pancreatic5 (14%)
     Other2 (6%)
     Unknown12 (34%)
    Functional status
     Nonfunctioning20 (57%)
     Functioning (carcinoid syndrome)15 (43%)
    Grade
     Low (G1)8 (23%)
     Intermediate (G2)21 (60%)
     High (G3)2 (6%)
     KI-67 proliferation index not available4 (11%)
    Primary tumor removed
     No20 (57%)
     Yes15 (43%)
    Previous treatments*
     Surgery15 (43%)
     Interferon α19 (54%)
     Somatostatin analogs14 (40%)
     Radiofrequency ablation (liver metastases)3 (9%)
     External radiation therapy1 (3%)
     Peptide receptor radionuclide therapy12 (34%)

    • ↵* Some patients received multiple treatments. Therefore, total number of treatments exceeded number of patients.

    • Data are n followed by percentage in parentheses, except for age.

  • TABLE 2

    Lesions per Organ or Region

    Visible on 64Cu-DOTATATE PET
    Organ or tissueConcordantOnly at 1 h after injectionOnly at 3 h after injectionP†
    Lung1400—
    Liver298020.98
    Intestines1800—
    Pancreas1200—
    Intraabdominal carcinomatosis700—
    Bone326111.00
    Lymph nodes114010.98
    Other*3300—
    Total822140.99

    • ↵* 22 soft-tissue lesions, 5 heart lesions, 1 prostate lesion, 1 adrenal lesion, 1 stomach lesion, 1 thyroid lesion, 1 brain lesion, and 1 spleen lesion.

    • ↵† Testing for differences in number of lesions with negative binominal regression on 64Cu-DOTATATE PET between 1 and 3 h after injection. The analyses are performed per organ or region and on the total number of lesions.

  • TABLE 3

    Discordant Lesions per Patient

    Visible on 64Cu-DOTATATE PET
    Patient no.ConcordantOnly at 1 h after injectionOnly at 3 h after injectionStatusMonths until follow-upFollow-up image modalityDiscordant organ system
    1Liver (11)LN (1)TP0*/9CT/CuLN
    2Bone (15), LN (7), lung (1), carc (1), liver (43)Bone (1)FP8CTNone
    3Liver (6), LN (8), int (1)Liver (1)TP46/46Ga/CTNone
    4Bone (19), spleen (1), int (1), adrenal (1), heart (3), liver (5)Bone (1)TP0*CTNone
    5Liver (2), LN (19) heart (2), int (1)Liver (1)TP39GaNone

    • ↵* Visible CT correlate on 64Cu-DOTATATE PET/CT.

    • LN = lymph nodes; TP = true-positive; Cu = follow-up 64Cu-DOTATATE PET at 1 h after injection; carc = intraabdominal carcinomatosis; FP = false-positive; int = intestines; Ga = 68Ga-DOTATOC PET.

  • TABLE 4

    Lesion SUVmax

    Lesion SUVmax on 64Cu-DOTATATE PET
    Organ or tissuen*1 h after injection3 h after injectionP†
    Lung517.9 [3.0–32.9]18.7 [5.3–32.1]1.00
    Liver2245.7 [37.2–54.3]54.1 [44.3–64.0]<0.01
    Intestines1264.4 [43.9–84.8]77.8 [52.3–103.3]0.19
    Pancreas879.0 [38.3–119.6]85.9 [35.9–135.8]1.00
    Bone1244.2 [25.7–62.7]50.1 [29.7–70.4]0.46
    Intraabdominal carcinomatosis423.0 [7.7–38.3]24.9 [9.0–40.7]1.00
    Lymph nodes18‡40.9 [26.9–54.9]43.5 [29.1–58.0]0.76

    • ↵* Number of patients with lesions.

    • ↵† Paired t testing with Bonferroni adjustment for multiple comparisons (n = 7) and capped at 1.00.

    • ↵‡ n = 19 on 64Cu-DOTATATE PET at 3 h after injection (one additional lymph node lesion detected in 1 patient).

    • Data are mean values followed by 95% confidence interval in brackets.

  • TABLE 5

    Normal-Organ SUVmean

    Normal-organ SUVmean† on 64Cu-DOTATATE PET
    Organ or tissuen*1 h after injection3 h after injectionP†
    Lung350.27 [0.23–0.30]0.15 [0.13–0.17]<0.01
    Liver324.0 [3.6–4.4]5.7 [5.2–6.3]<0.01
    Intestines352.6 [2.1–3.1]2.5 [2.0–3.1]1.00
    Uncinate process of pancreas313.2 [2.7–3.6]3.3 [2.7–3.9]1.00
    Cauda of pancreas323.1 [2.8–3.5]3.5 [3.2–3.9]0.38
    Bone350.76 [0.66–0.85]0.64 [0.56–0.73]<0.01
    Muscle350.63 [0.57–0.69]0.49 [0.44–0.54]<0.01
    Spleen358.9 [7.8–10.0]9.3 [8.2–10.4]0.12
    Pituitary gland3512.9 [10.8–14.9]15.8 [13.4–18.2]<0.01
    Adrenal gland339.5 [8.0–11.0]9.9 [8.2–11.6]1.00

    • ↵* Number of patients with evaluable normal organs.

    • ↵† Paired t testing with Bonferroni adjustment for multiple comparisons (n = 10) and capped at 1.00.

    • Data are mean values followed by 95% confidence interval in brackets.

  • TABLE 6

    TTN

    TTN†
    Organ or tissuen*1 h after injection of 64Cu-DOTATATE3 h after injection of 64Cu-DOTATATEP†
    Lung587.9 [30.2–145.6]160.9 [79.2–242.6]0.04
    Liver1912.6 [10.2–14.9]11.0 [8.7–13.4]0.03
    Intestines1224.2 [14.9–33.4]28.2 [16.5–40.0]0.73
    Pancreas642.4 [12.3–72.5]41.1 [8.7–73.4]1.00
    Bone12103.0 [38.6–167.4]124.2 [57.1–191.2]0.07
    Intraabdominal carcinomatosis414.0 [3.0–25.0]22.5 [7.1–38.0]0.50
    Lymph nodes18‡73.7 [43.0–104.4]94.0 [61.6–126.4]0.07

    • ↵* Number of patients with lesions and evaluable normal tissue.

    • ↵† Paired t testing with Bonferroni adjustment for multiple comparisons (n = 7) and capped at 1.00.

    • ↵‡ n = 19 on 64Cu-DOTATATE PET at 3 h after injection (one additional lymph node lesion detected in 1 patient).

    • Data are mean values followed by 95% confidence interval in brackets.

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