PT  - JOURNAL ARTICLE
AU  - Jingjing Zhang
AU  - Hao Wang
AU  - Orit Jacobson Weiss
AU  - Yuejuan Cheng
AU  - Gang Niu
AU  - Fang Li
AU  - Chunmei Bai
AU  - Zhaohui Zhu
AU  - Xiaoyuan Chen
TI  - Safety, Pharmacokinetics and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analogue <sup>177</sup>Lu-DOTA-EB-TATE in Patients with Advanced Metastatic Neuroendocrine Tumors
AID  - 10.2967/jnumed.118.209841
DP  - 2018 Apr 01
TA  - Journal of Nuclear Medicine
PG  - jnumed.118.209841
4099  - http://jnm.snmjournals.org/content/early/2018/04/12/jnumed.118.209841.short
4100  - http://jnm.snmjournals.org/content/early/2018/04/12/jnumed.118.209841.full
AB  - Radiolabeled somatostatin analogue therapy has become an established treatment method for patients with well to moderately differentiated unresectable or metastatic neuroendocrine tumors (NETs). The most frequently used somatostatin analogues in clinical practice are octreotide and octreotate. However, both peptides showed suboptimal retention within tumors. The aim of this first-in-human study is to explore the safety and dosimetry of a long-acting radiolabeled somatostatin analogue, lutetium-177-1, 4, 7, 10-tetra-azacyclododecane-1, 4, 7, 10-tetraacetic acid-Evans blue-octreotate (177Lu-DOTA-EB-TATE). Methods: Eight patients (6 males and 2 females; age range, 27–61 y) with advanced metastatic neuroendocrine tumors were recruited. Five patients received a single dose 0.35-0.70 GBq (9.5-18.9 mCi) of 177Lu-DOTA-EB-TATE and underwent serial whole body planar and single-photon emission computed tomography-computed tomography (SPECT-CT) scans at 2, 24, 72, 120 and 168 h after injection. The other 3 patients received intravenous injection of 0.28-0.41 GBq (7.5-11.1 mCi) of 177Lu-DOTATATE for the same imaging acquisition procedures at 1, 3, 4, 24 and 72 h after injection. The dosimetry was calculated using the OLINDA/EXM 1.1 software. Results: Administration of 177Lu-DOTA-EB-TATE was well tolerated, with no adverse symptoms being noticed or reported in any of the patients. Compared with 177Lu-DOTATATE, 177Lu-DOTA-EB-TATE showed extended circulation in the blood and achieved 7.9-fold increase of tumor dose delivery. The total body effective doses were 0.205 ± 0.161 mSv/MBq for 177Lu-DOTA-EB-TATE and 0.174 ± 0.072 mSv/MBq for 177Lu-DOTATATE. Significant dose delivery increases to the kidneys and bone marrow were also observed in patients receiving 177Lu-DOTA-EB-TATE than those receiving 177Lu-DOTATATE (3.2 and 18.2-fold, respectively). Conclusion: By introducing an albumin binding moiety, 177Lu-DOTA-EB-TATE showed remarkably higher uptake and retention in NET tumors as well as significantly increased accumulation in the kidneys and red marrow. It has great potential to be used in PRRT for NET tumors with lower dose and less frequency of administration.