Article Figures & Data
Figures
- FIGURE 1.
Representative planar whole-body anterior and posterior scintigraphic images of patient with pancreatic NEN liver metastases at various times after intravenous administration of 5.3 GBq of 177Lu-DOTA-LM3. Intense tumor uptake in liver metastases (arrows) was observed, as well as pulmonary uptake (at 0.5 and 2.5 h) and significant uptake in kidneys, spleen, and liver (at 0.5, 2.5, 19.5, 44.0, and 68.5 h). ANT = anterior; POST = posterior.
- FIGURE 2.
Biodistribution, effective half-life, and mean absorbed organ and tumor doses of 177Lu-DOTA-LM3. Longest effective half-life was obtained in metastases. Spleen had highest absorbed dose of all analyzed normal organs. Higher uptake, longer effective half-life, and higher mean absorbed doses in liver metastases than in bone lesions were observed. All results showed high variability, as demonstrated by error bars, which represent SD. p.i. = after injection.
- FIGURE 3.
(A) Comparison of biodistribution and dosimetry results of antagonist 177Lu-DOTA-LM3 (n = 11) and agonist 177Lu-DOTATOC (n = 247). Higher uptake and longer effective half-life were found for 177Lu-DOTA-LM3 in whole body as well as kidneys, spleen, and metastases, resulting in higher mean absorbed organ and tumor doses for 177Lu-DOTA-LM3 than for 177Lu-DOTATOC. (B) Example of 177Lu-DOTA-LM3 and 177Lu-DOTATOC in same patient. p.i. = after injection.
- FIGURE 4.
(A–D) Comparison of hemoglobin (A), leukocyte count (B), platelet count (C), and neutrophil count (D) before and after 177Lu-DOTA-LM3 PRRT. (E and F) Comparison of serum creatinine (E) and renal function quantified by measuring tubular extraction rate using 99mTc-mercaptoacetyltriglycine renal scintigraphy (F) before and after 177Lu-DOTA-LM3 PRRT, which did not reveal any significant nephrotoxicity.
- FIGURE 5.
A 55-y-old man with well-differentiated, nonfunctioning metastatic pancreatic NEN and Ki-67 index of 13%. Patient underwent Whipple procedure, with histologically confirmed G2 pancreatic NEN. MRI had revealed multiple small-volume liver metastases. 68Ga-DOTATATE PET/CT showed weakly 68Ga-DOTATATE–avid small-volume lesions in liver and lymph nodes with extremely low uptake (leftmost image), which did not exhibit significant glucose hypermetabolism (second image from left). 68Ga-NODAGA-LM3 PET/CT then showed disseminated bilobar liver metastases, demonstrating intense SSTR antagonist (LM3) uptake in liver and lymph node metastases (third image from left). Patient was treated with 4 cycles of 177Lu-DOTA-LM3 PRRT, with cumulative administered radioactivity of 25.7 GBq. Restaging 68Ga-NODAGA-LM3 PET/CT showed excellent response to 177Lu-DOTA-LM3 PRRT, with partial remission of disease according to RECIST and EORTC criteria (rightmost image).
Tables
Characteristic Data Sex Male 33 (64.7%) Female 18 (35.3%) Age, mean ± SD (y) 51.6 ± 13.9 Primary tumor site Cancer of unknown primary (CUP) 7 (13.7%) Pancreas 13 (25.5%) Midgut 15 (29.4%) Rectum 3 (5.9%) Lung 4 (7.8%) Other 9 (17.6%) Functional vs. nonfunctional Functional NEN 26 (51.0%) Nonfunctional NEN 25 (49.0%) Ki-67 index grading G1 (Ki-67 < 3%) 14 (27.5%) G2 (Ki-67 = 3%–20%) 27 (52.9%) G3 (Ki-67 > 20%) 10 (19.6%) Primary treatment before PRRT Surgery 36 (70.6%) Somatostatin analog 32 (62.7%) Chemotherapy 11 (21.6%) Liver-directed therapy 12 (23.5%) TACE 7 (13.7%) SIRT (radioembolization) 2 (3.9%) Other 3 (5.9%) Everolimus 7 (13.7%) External-beam radiotherapy 8 (15.7%) Previously treated with 177Lu-DOTATOC/TATE PRRT Yes 35 (68.6%) No (PRRT-naïve patients) 16 (31.4%) Data are number followed by percentage in parentheses, except for age.
- TABLE 2
Treatment Cycles and Cumulative Administered Radioactivity for 177Lu-DOTA-LM3 PRRT (n = 51)
Cumulative radioactivity (GBq) Variable n % Mean SD No. of 177Lu-LM3 PRRT cycles 51 100 1 25 49.0 6.1 0.8 2 15 29.4 11.4 2.1 3 7 13.7 19.4 1.1 4 4 7.8 26.0 1.2 No. of 177Lu-LM3 PRRT cycles in patients previously treated with TOC/TATE PRRT 35 68.6 1 25 49.0 6.1 0.8 2 6 11.8 10.9 1.5 3 3 5.9 18.8 1.2 4 1 2.0 25.6 / No. of 177Lu-LM3 PRRT cycles in PRRT-naïve patients 16 31.4 2 9 17.6 12.0 2.5 3 4 7.8 19.9 0.8 4 3 5.9 26.1 1.4 - TABLE 3
Hematotoxicity and Nephrotoxicity Before and After 177Lu-DOTA-LM3 PRRT According to Common Terminology Criteria for Adverse Events, Version 5.0
Anemia Leukocytopenia Thrombocytopenia Lymphopenia Neutropenia Nephrotoxicity Grade Before After Before After Before After Before After Before After Before After CTC-1 10 18 2 5 6 9 9 15 1 2 6 7 CTC-2 6 5 1 3 1 0 8 5 0 2 4 2 CTC-3 0 0 0 0 0 3 1 4 0 0 0 0 CTC-4 0 0 0 0 0 0 0 0 0 0 0 0 CTC-5 NA 0 NA 0 NA 0 NA 0 NA 0 NA 0 NA = not applicable before 177Lu-DOTA-LM3 PRRT (grade 5 represents death).
Data are numbers of patients.
Total (n = 47) PRRT-naïve (n = 14) Previously treated with TOC/TATE PRRT (n = 33) Response n % n % n % RECIST CT or MRI response Complete response 0 0 0 0 0 0 Partial response 17 36.2 10 71.4 7 21.2 Stable disease 23 48.9 3 21.4 20 60.6 Progressive disease 7 14.9 1 7.1 6 18.2 Disease control rate 40 85.1 13 92.9 27 81.8 EORTC SSTR imaging response Complete response 2 4.3 1 7.1 1 3.0 Partial response 21 44.7 9 64.3 12 36.4 Stable disease 18 38.3 3 21.4 15 45.5 Progressive disease 6 12.8 1 7.1 5 15.2 Disease control rate 41 87.2 13 92.9 28 84.8
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