Imaging of lymph flow in breast cancer patients after microdose administration of a near-infrared fluorophore: feasibility study.
OBJECTIVE
To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM).


METHODS
Informed consent was obtained from 24 women (age range, 30-85 years) who received intradermal subcutaneous injections of 0.31-100 microg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively.


RESULTS
Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 microg. When indocyanine green dosages were 10 microg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between "packets" of propelled fluid varied from 14 to 92 seconds. In patients who received 10 microg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of NIR fluorophore.


CONCLUSIONS
NIR fluorescence imaging of lymph function and LNs is feasible in humans at microdoses that would be needed for future molecular imaging of cancer-positive LNs.
Sevick-Muraca
Eva M
EM
Department of Radiology, Division of Molecular Imaging, Baylor College of Medicine, One Baylor Plaza, BCM 360, Houston, TX 77030, USA. evas@bcm.tmc.edu
Sharma
Ruchi
R
Rasmussen
John C
JC
Marshall
Milton V
MV
Wendt
Juliet A
JA
Pham
Hoang Q
HQ
Bonefas
Elizabeth
E
Houston
Jessica P
JP
Sampath
Lakshmi
L
Adams
Kristen E
KE
Blanchard
Darlene Kay
DK
Fisher
Ronald E
RE
Chiang
Stephen B
SB
Elledge
Richard
R
Mawad
Michel E
ME
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001365:Axilla; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D005240:Feasibility Studies; D005260:Female; D005456:Fluorescent Dyes; D015902:Gamma Cameras; D006801:Humans; D007208:Indocyanine Green; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D011877:Radionuclide Imaging; D021701:Sentinel Lymph Node Biopsy; D013249:Sternum
D005456:Fluorescent Dyes; D007208:Indocyanine Green