Indocyanine Green (ICG)
Indocyanine green (ICG) is a tricarbocyanine near-infrared (NIR) fluorescent dye that binds rapidly to plasma proteins after IV injection and is cleared almost exclusively by hepatic excretion into bile, with a plasma half-life of 3–4 minutes. When excited by 750–800 nm light, ICG emits at 830 nm, a wavelength that is invisible to the naked eye but visualized by dedicated NIR imaging systems (Firefly, SPY, Rubina, PINPOINT). This combination (rapid plasma binding, rapid clearance, biliary excretion, and NIR emission through several millimeters of tissue) makes ICG the dominant intraoperative fluorophore in GU reconstruction.[1][2]
Pharmacology
| Property | Value |
|---|---|
| Class | Tricarbocyanine NIR fluorescent dye |
| Molecular weight | 775 Da |
| Plasma half-life | 3–4 minutes |
| Protein binding | 98% (plasma proteins)[5] |
| Distribution | Predominantly intravascular initially |
| Clearance | Hepatic — excreted into bile; no renal or urinary excretion |
| Peak excitation | ~800 nm |
| Peak emission | ~830 nm |
| FDA approval | Current IC-GREEN label includes vessels, blood flow and tissue perfusion; retrograde urinary instillation and GU sentinel mapping remain off-label |
Why the pharmacology matters
- Rapid plasma half-life means multiple doses can be given per case as anatomy evolves
- No urinary excretion. ICG given IV does not appear in urine. IV ICG can instead assess perfusion of an exposed ureteral segment before anastomosis, but it does not fill the urinary column or reliably trace an unexposed ureter.[5][6][10]
- Biliary excretion. ICG can faintly highlight the biliary tree, which is rarely clinically relevant in GU work but worth knowing
Dosing
IV perfusion dosing — current US IC-GREEN label
For an adult image sequence, 1.25–5 mg IV, followed immediately by a 10 mL saline flush. For extremity perfusion through skin, the adult range is 3.75–10 mg. Additional sequences may be obtained during the procedure, without exceeding 2 mg/kg total. This is a ceiling, not a target or a fixed repeat-every-5-minutes protocol. Reconstitute the 25 mg vial with 10 mL Sterile Water for Injection (2.5 mg/mL); other vial presentations have their own instructions. Use within 6 hours and discard unused solution. Use an imaging device authorized for the intended ICG application.[5]
Direct urinary instillation and lymphatic mapping
Retrograde intraureteral or intravesical ICG is off-label. Concentration, volume and catheter handling should follow a defined specialist protocol; published case-series recipes are not interchangeable with the IV label. Penile or prostate lymphatic mapping also must not borrow a generic injection recipe from the separately labeled cervical or uterine cancer indication. Do not force injection against resistance. One 2025 case report describes anuria and temporary dialysis for acute kidney injury of uncertain cause after bilateral intraureteral ICG instillation during endometrioma excision.[19]
Hypersensitivity and iodide
The January 2026 US IC-GREEN label contraindicates use in patients with hypersensitivity to indocyanine green. It does not list shellfish allergy or a nonspecific “iodine allergy” as that contraindication. Clarify the actual prior drug and reaction, check the specific product label, and obtain allergy or anesthesia input when needed. Anaphylaxis, including fatal reactions, has occurred: monitor every patient and have resuscitation personnel and equipment available. Sodium iodide in IC-GREEN can interfere with thyroid radioiodine uptake for at least one week.[5]
GU Reconstruction Applications
1. Perfusion assessment
The original and highest-yield urologic application. IV ICG fluorescence can help assess blood flow and tissue perfusion of an exposed ureteral stump, bowel mesentery before urinary diversion, bladder and phalloplasty flaps, and omental pedicles.[5]
- Ureter after reimplantation. Helps assess perfusion of the distal segment after dissection
- Ureter before ureteroenteric anastomosis. IV ICG (or SPY in open surgery) permits trimming to well-perfused ureter. In a non-randomized RARC cohort with extracorporeal diversion, 196 ICG recipients versus 196 prior controls had estimated stricture risk at 6 months of 2% versus 12% and at 24 months of 3% versus 14% (adjusted HR 0.20, 95% CI 0.08–0.50).[6] In a non-randomized open-diversion cohort with unequal median follow-up (17.5 versus 58.6 months), strictures occurred in 1/55 SPY patients versus 31/277 historic controls (1.8% versus 11.1%).[7] In a separate 221-patient RARC cohort with intracorporeal diversion (median follow-up 21.1 months), benign ureteroenteric stricture occurred in 15/79 (19.0%) ICG recipients and 26/142 (18.3%) controls.[18] Across four observational robotic-cystectomy comparisons (886 patients; 1,739 ureters), a 2026 meta-analysis estimated a per-ureter RR of 0.31 (95% CI 0.08–1.16; I² 76.4%); certainty was very low.[12]
- Ileal conduit before anastomosis. Helps assess bowel-segment perfusion
- Kidney perfusion during partial nephrectomy. A retrospective series describes IV ICG after pedicle clamping to confirm ischemia, followed by unclamping to identify the tumor margin and reclamping before excision.[3]
- Bladder flap for Boari. Helps assess perfusion of the flap before tubularization
- Omental flap. May supplement visual assessment of pedicle perfusion after mobilization
- Bowel anastomosis in urinary diversion. Early identification of poorly perfused anastomotic segments. The randomized evidence is colorectal: a 2026 meta-analysis of nine RCTs (4,754 patients) found ICG angiography lowered anastomotic leak (RR 0.66), with benefit in left-sided and rectal resections but not right-sided ones.[8] Whether this benefit extends to ileo-ileal or ileocolonic anastomoses in urinary diversion was not tested in these trials.[8]
2. Ureteral identification
Two distinct techniques (IV versus intraureteral):
Intraureteral ICG (retrograde):
- Ureteral catheter placed cystoscopically; instillation proceeds retrograde according to the local protocol
- The urinary column within the ureter fluoresces under NIR imaging
- An adjunct for intraoperative ureter localization during robotic pelvic surgery. A 2026 meta-analysis (17 mostly non-randomized ICG studies, 569 patients, versus 20 stent studies) found injection succeeded in every ureter and reported ureteral injury of 0.18% versus 1.12% with stents. There are no head-to-head trials, so ICG is not shown to replace stents[9]
- In robot-assisted ureteral reconstruction, ICG injected off-label into the diseased ureter above and below the stricture (through a ureteral catheter, a nephrostomy tube or both) was used to identify the ureter and localize the proximal and distal stricture margins under NIR imaging. In a retrospective series of 26 reconstructions in 25 patients (ureterolysis, pyeloplasty, ureteroureterostomy and ureteroneocystostomy), there were no perioperative complications attributed to ICG, and all procedures were clinically and radiologically successful at a mean follow-up of 12 months; the series was small and short-term[10]
IV ICG for ureter:
- IV injection does not fill the ureter (no urinary excretion)
- IV ICG has been used to assess perfusion of an exposed distal ureter before anastomosis[6][7]
- Intraureteral instillation is the reported ICG method for tracing the ureteral course beneath overlying tissue[9][10]
- See also pudexacianinium (ASP-5354), an investigational IV NIR agent that is excreted into urine
3. Lymphatic mapping
- Pelvic lymph node dissection during radical prostatectomy, cystectomy (within functional-urology scope where it overlaps)
- Sentinel node mapping in penile cancer (outside primary WARWIKI scope but referenced for completeness)
- The US label covers lymphatic mapping only in cervical and uterine cancer (interstitial); urologic use is off-label
- Intradermal or peritumoral ICG injection, then lymphatic channels fluoresce, then sentinel node identification
4. Vesicourethral / bladder-neck identification (robotic)
- Y-V plasty for bladder-neck or vesicourethral stenosis. In Granieri’s seven-patient robotic series (six bladder-neck contractures and one vesicourethral anastomotic stenosis), a cystoscope was advanced to the narrowing and Firefly was used for localization. Kurobe and colleagues classify this as near-infrared cystoscopic transillumination without ICG injection. See Y-V plasty.[4][11]
- Vesicourethral anastomotic stenosis repair. Similar rationale
5. Penile reconstruction
- Perfusion assessment after Peyronie's degloving
- Phalloplasty flap assessment. RFFF, ALT, SCIP perfusion
- Penile shaft coverage flap viability
6. Fistula localization (emerging)
Intravesical ICG appears among dye options in a specialist description of the diagnostic VVF tampon test; methylene blue is usually used.[13] In one VVF repair within a 37-case urologic series, IV ICG was used to assess bladder and vaginal-wall perfusion during repair.[14]
NIR Imaging Hardware
ICG fluorescence requires dedicated imaging:
| System | Platform | Workflow |
|---|---|---|
| Firefly | Intuitive da Vinci (Si, Xi, X, SP, 5) | Toggle between white-light and NIR modes at the console |
| SPY-PHI | Stryker (open-field imaging) | Handheld NIR imager for blood flow and tissue perfusion[15] |
| PINPOINT | Novadaq/Stryker | Laparoscopic NIR video system |
| IMAGE1 S Rubina | Karl Storz | Laparoscopic NIR with side-by-side display |
| Visera Elite III | Olympus | Laparoscopic NIR |
Firefly is integrated into da Vinci systems; SPY-PHI is a handheld open-field imager, PINPOINT and VISERA ELITE III are endoscopic platforms, and IMAGE1 S Rubina supports endoscopic and open-field imaging with the Rubina Lens.[15][20][21][22]
Technique Pearls
- Give the bolus at the right moment. The label expects vessel fluorescence within 5–15 seconds; tissue-level perfusion may take longer. Coordinate with anesthesia so the bolus is given just before the assessment rather than 5 minutes ahead
- Bolus timing. Give IV ICG just before perfusion assessment; residual background fluorescence can persist between imaging sequences despite the short plasma half-life.[5][17]
- Track cumulative dose and residual background fluorescence; fluorescence intensity depends on dose, timing, camera settings and tissue conditions
- Intraureteral retrograde dosing is generally used rather than IV when the goal is to see the ureteral course
- Firefly auto-gain can over-brighten adjacent tissues; toggle the NIR view intermittently to recalibrate
- Clarify prior dye reactions; alternative dyes have their own risks and pudexacianinium remains investigational
Adverse Events
ICG has 65+ years of clinical use with the following safety profile:
- Anaphylaxis. Potentially fatal.[5]
- Other reported reactions. The US IC-GREEN label lists urticaria without an estimable frequency; the UK Verdye label also lists nausea and describes flushing among symptoms of anaphylactoid reactions.[5][16]
- Predominantly hepatic clearance. Does not require urinary excretion for perfusion imaging
- ICG is not a gadolinium contrast agent; apply its own label and hypersensitivity precautions
Interpretation and cost
ICG highlights fluorescence associated with delivery and tissue uptake. Standardized thresholds and improvement in clinical outcomes remain procedure-specific questions. Acquisition prices vary by product and contract; the imaging system and workflow contribute to total cost.
See Also
- Visualization agents overview
- Methylene blue
- Pudexacianinium (ASP-5354)
- Y-V plasty (cystoscope-guided Firefly localization)
- Robotics platforms
Videos
References
1. Alander JT, Kaartinen I, Laakso A, et al. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging. 2012;2012:940585. doi:10.1155/2012/940585
2. Reinhart MB, Huntington CR, Blair LJ, Heniford BT, Augenstein VA. Indocyanine green: historical context, current applications, and future considerations. Surg Innov. 2016;23(2):166–75. doi:10.1177/1553350615604053
3. Yang YK, Hsieh ML, Chen SY, Liu CY, Lin PH, Kan HC, Pang ST, Yu KJ. Clinical benefits of indocyanine green fluorescence in robot-assisted partial nephrectomy. Cancers (Basel). 2022;14(12):3032. doi:10.3390/cancers14123032
4. Granieri MA, Weinberg AC, Sun JY, Stifelman MD, Zhao LC. Robotic Y-V plasty for recalcitrant bladder neck contracture. Urology. 2018;117:163–165. doi:10.1016/j.urology.2018.04.017
5. IC-GREEN. US prescribing information, revised January 2026. DailyMed.
6. Lama DJ, Jaime-Casas S, Hudnall M, et al. Evaluation of long-term outcomes utilizing indocyanine green to decrease ureteroenteric anastomotic stricture during robotic radical cystectomy and extracorporeal urinary diversion. Eur Urol Open Sci. 2025;81:5-12. doi:10.1016/j.euros.2025.06.004
7. Yeaman C, Ignozzi G, Kazeem A, et al. Impact of SPY fluorescence angiography on incidence of ureteroenteric stricture after urinary diversion. J Urol. 2024;212(6):844-850. doi:10.1097/JU.0000000000004198
8. Ryan ÉJ, Ryan OK, Corrigan N, et al. Indocyanine green fluorescence angiography for anastomotic perfusion assessment in colorectal surgery: a systematic review with meta-analysis, meta-regression, and trial sequential analyses. Lancet Gastroenterol Hepatol. 2026;11(5):367-379. doi:10.1016/S2468-1253(25)00373-5
9. Goldhawk-White PE, White KP, Nezhat C, et al. Retrograde intraureteral injections of indocyanine green versus ureteral stents to reduce urinary tract complications during pelvic surgery: systematic review and meta-analysis. Surgery. 2026;192:110047. doi:10.1016/j.surg.2025.110047
10. Lee Z, Moore B, Giusto L, Eun DD. Use of indocyanine green during robot-assisted ureteral reconstructions. Eur Urol. 2015;67(2):291-298. doi:10.1016/j.eururo.2014.08.057
11. Kurobe M, Ogawa T, Satoh Y, et al. "Near infrared ray-guided partial cystectomy using da Vinci Firefly technology and intraoperative cystoscopy for urachal cyst, suspected of urachal tumor." Investig Clin Urol. 2026;67(2):178-185. doi:10.4111/icu.20250141
12. Nominato EO, Miranda AARR, Fernandes MEM, et al. "Intraoperative indocyanine green fluorescence guidance to reduce ureteroenteric anastomotic strictures during robot-assisted radical cystectomy. A systematic review and meta-analysis." Urol Oncol. Published online September 3, 2026. doi:10.1016/j.urolonc.2026.08.003
13. Copeland LJ. "Postoperative Urinary Fistulae." Exxcellence Clinical Pearls. Society for Academic Specialists in General Obstetrics and Gynecology; updated September 3, 2024. Clinical pearl.
14. Petrut B, Bujoreanu CE, Porav-Hodade D, et al. "Indocyanine green use in Urology." J BUON. 2021;26(1):266-274. PMID:33721461. Full text.
15. Stryker. "SPY PHI Fluorescence Imaging." Manufacturer product specifications. Product page. Accessed October 3, 2026.
16. Diagnostic Green Limited. "Verdye 5 mg/ml Powder for solution for injection: Summary of Product Characteristics." UK electronic Medicines Compendium. Updated September 4, 2026. SmPC.
17. Lee BT, Hutteman M, Gioux S, et al. "The FLARE intraoperative near-infrared fluorescence imaging system: a first-in-human clinical trial in perforator flap breast reconstruction." Plast Reconstr Surg. 2010;126(5):1472–1481. doi:10.1097/PRS.0b013e3181f059c7
18. Carbonell E, Sierra A, Mercader C, et al. "Intravenous indocyanine green to evaluate distal ureteral vascularity during robot-assisted radical cystectomy with intracorporeal urinary diversion." World J Urol. 2024;42(1):568. doi:10.1007/s00345-024-05284-8
19. Scholz A, Redko O, Kostrzanowski M, Dąbrowski F. "First reported case of acute kidney injury following intraureteral indocyanine green administration during bilateral endometrioma excision." J Clin Med. 2025;14(24):8758. doi:10.3390/jcm14248758
20. Stryker. "PINPOINT Endoscopic Fluorescence Imaging." Manufacturer product specifications. Product page. Accessed October 8, 2026.
21. KARL STORZ. "KARL STORZ Announces FDA Clearance for RUBINA Lens for Open Surgery." Press release, October 6, 2026. Manufacturer page.
22. Olympus America. "VISERA ELITE III Multispecialty Surgical Imaging Platform." Manufacturer product specifications. Product page. Accessed October 8, 2026.