title: Poly(Lactide-co-glycolide) ultrasonographic microbubbles carrying Sudan black for preoperative and intraoperative localization of lymph nodes.
abstract: Lymph node (LN) examination plays a critical role in the staging and treatment of several kinds of cancer such as lesions of the breast. However current strategies have limitations. This study aimed to develop a novel imaging agent, a polymeric ultrasonographic contrast agent carrying Sudan black (SB), for ultrasonographic imaging of the regional LNs before surgery and to directly localize the LNs during surgery. The poly(lactide-co-glycolide) (PLGA) ultrasonographic microbubbles carrying Sudan black B (SB) (SB-PLGA microbubbles) were prepared by the double emulsion method. The SB-PLGA microbubbles had a diameter of 1.5 ± 0.5 μm and the SB encapsulation efficiency was (86.2 ± 1.56%). Results from MTT assays suggested that these bubbles have little cytotoxicity to mouse macrophages after incubation. Confocal laser scanning microscopy showed that the PLGA microbubbles carrying the fluorescent dye rhodamine 6G were taken up by macrophages after 2-hour incubation. In addition, these SB-PLGA microbubbles were able to enhance ultrasonographic contrast of 12 popliteal LNs of 6 rabbits. Furthermore, the LNs were easily identifiable by the naked eye during surgery because of the blue color of the SB-PLGA microbubbles inside the LNs. By cryosectioning and hematoxylin and eosin (H&E) staining of LN tissue, our results showed that these SB-PLGA microbubbles were internalized inside the macrophages of the LNs. To conclude, the SB-PLGA microbubbles could be a suitable imaging agent for preoperative and intraoperative localization of LNs as well as for a preoperative ultrasonographically guided core needle biopsy of suspicious sentinel lymph nodes (SLNs) in cancer patients, hence enhancing treatment outcome.
authors.affiliation: Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Niu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zuo
authors.forename: Tianyi M
authors.initials: TM
authors.lastname: Krupka
authors.forename: Haitao
authors.initials: H
authors.lastname: Ran
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Pan
authors.initials: P
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Hangrong
authors.initials: H
authors.lastname: Chen
authors.forename: Yuanyi
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D002478:Cells, Cultured; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D007432:Intraoperative Period; D019344:Lactic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging / Q000473:pathology; D051379:Mice; D045423:Microbubbles; D009281:Naphthalenes; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D057234:Preoperative Period; D011817:Rabbits; D021701:Sentinel Lymph Node Biopsy / Q000295:instrumentation / Q000379:methods*; D018084:Ultrasonography, Interventional / Q000295:instrumentation / Q000379:methods
chemical_list: D001391:Azo Compounds; D003287:Contrast Media; D004337:Drug Carriers; D009281:Naphthalenes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C016118:Sudan Black B