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Near-infrared fluorescence imaging (NIRFI) is a new noninvasive detection and diagnosis technology, with the continuous development of NIRFI technology, now widely used in the clinic, characterized by high sensitivity, high penetration, no harmful radiation and simple equipment operation. This article describes the recent applications of NIRFI in the diagnosis and treatment of breast cancer and looks at future developments and perspectives in this field.
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Objective @# To investigate the application of indocyanine green in near-infrared fluorescence imaging to determine the scope of necrotic bone resection in osteoradionecrosis of the jaw and to provide a reference for clinicians@*Methods @#Eight patients with osteoradionecrosis of the jaws were enrolled. Indocyanine green was intravenously injected through the elbow vein 10 minutes before osteotomy. After conservative resection of necrotic bone lesions based on imaging results, the scope of potential dead bone resection in the area of low fluorescence intensity was gradually expanded at an initial distance of 0.3 cm. Near-infrared fluorescence imaging and fluorescence intensity determination of bone cross-section were performed before and after extended resection. Statistical differences were analyzed. All patients with osteonecrosis underwent regular follow-up to evaluate the postoperative efficacy@*Results@#Indocyanine green was injected into all 8 patients with osteoradionecrosis for near-infrared fluorescence imaging and the scans were clear; the fluorescence intensity of fresh bone wounds with an expanded mandibular resection range of (0.95 ± 0.14) cm was (226.2 ± 15.8) au, which was higher than that based on intraoperative macroscopic observation and radiological results (108.8 ± 3.4) au, (t = 20.718, P<0.001). The postoperative follow-up improvement rate of 8 patients was 87.5%.@* Conclusion @#Near-infrared fluorescence imaging with indocyanine green can assist in the successful removal of necrotic bone until fresh bleeding of the jaw wound occurs, which has important clinical value in defining the resection range of osteoradionecrosis of the jaw.
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Objective:To investigate the feasibility and clinical significance of near-infrared fluorescence positive imaging combined with intraoperative rapid parathyroid hormone (PTH) determination in identification and function protection of the parathyroid gland during thyroidectomy.Methods:According to the inclusion and exclusion criteria, patients in the Affiliated Lihuili Hospital of Ningbo University, who needed bilateral thyroidecto-my and central lymph node dissection due to suspected bilateral thyroid cancer from Mar. 2020 to Oct. 2020 were selected for a prospective clinical study. They were randomly divided into the study group (near-infrared fluorescence positive imaging combined with intraoperative rapid PTH determination) and the control group (intraoperative experience identification) . The number of parathyroid glands found during operation, PTH before and after the operation, blood calcium, blood phosphorus, the presence of parathyroid tissues in routine pathological section examinations, and postoperative symptoms were collected. SPSS 25.0 statistical software was used for analysis, the measurement data were expressed by mean±standard deviation ( ± s) , t test was used for comparison between groups, and χ2 test was used for counting date. Results:In the study group of 33 cases, 135 suspicious parathyroid glands were exhibited during operation, with an average of (4.09±0.52) ; Hand and foot numbness occurred in 1 case (3.03%) ; On the 1st after the operation, PTH was (23.68±9.48) ng/L. In the control group of 31 cases, 109 parathyroid glands were identified by naked eyes, with an average of (3.52±0.63) ; Hand and foot numbness occurred in 6 cases (19.35%) ; On the 1st after the operation, PTH was (17.93±11.58) ng/L. The differences were statistically significant ( P<0.05) . But no statistical significance was found in operation duration (79.45±30.18) min, postoperative hospitalization days (5.85±2.27) days, PTH (27.10±9.80, 33.08±10.21) ng/L, blood calcium (2.11±0.10,2.25±0.09) mmol/L, and blood phosphorus (1.20±0.20,1.15±0.12) mmol/L on the 3rd day and the 6th month after the operation. Conclusion:Near-infrared fluorescence positive imaging combined with intraoperative rapid PTH determination can improve the recognition rate of the parathyroid gland and reduce postoperative complications, which is a safe, effective and rapid method for intraoperative parathyroid gland recognition.
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Objective: Local recurrence is the main cause of treatment failure in patients with oral squamous cell carcinoma (OSCC). This study was proposed to investigate the feasibility of near infrared fluorescence (NIF) via indocyanine green (ICG) for monitoring surgical marginal in operation for OSCC patients. Methods: In 35 patients with OSCC treated surgically in the Department of Oral and Maxillofacial Surgery, Nanjing University School of Medicine, from January 2019 to June 2020, ICG (0.75 mg/kg) was administered intravenously via elbow vein at (12±1) hours before surgery, and NIF was performed intraoperatively on the surgical field and the cut edge of the surgically excised specimen, and fluorescence intensity was measured for OSCC tissue and normal oral mucosa, abnormal fluorescence signals were taken and subjected to rapid cryopathological examination. Correlation between NIF tumor boundary grading and pathological tumor boundary grading was analyzed by Spearman correlation analysis. Results: Clear ICG NIF was obtained for tumor lesions in all 35 patients, with a positive rate of 100%. The fluorescence intensity of OSCC tissue was (412.73±146.56) au, which was higher than that of normal oral mucosa tissue [(279.38±82.56) au, P<0.01]. Abnormal fluorescence signals were detected at the tumor bed and the cut edge of the surgical resection specimen in 4 patients, of which 2 cases were pathologically confirmed as cancer cell residue and 2 cases as inflammatory cell infiltration. The rate of positive detection of cut margins using ICG NIF technique in OSCC was 5.7% (2/35). Twenty of the 35 OSCC patients had grade 1, 11 of grade 2, and 4 of grade 3 tumor borders revealed by NIF of surgical resection specimens, which was positively correlated with pathological tumor border (r=0.809, P<0.001). Conclusions: ICG NIF technique can effectively detect the residual cancer cells at the incision margin, which is of great clinical value in reducing local recurrence of OSCC after surgery due to intraoperative cancer residue.
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Humans , Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms , Indocyanine Green , Margins of Excision , Mouth Neoplasms/surgery , Neoplasm, Residual , Optical Imaging/methods , Squamous Cell Carcinoma of Head and Neck/surgeryABSTRACT
Fluorescence imaging has been widely used in the fields of biomedicine and clinical diagnosis. Compared with traditional fluorescence imaging in the visible spectral region (400-760 nm), near-infrared (NIR, 700-1 700 nm) fluorescence imaging is more helpful to improve the signal-to-noise ratio and the sensitivity of imaging. Highly-sensitive fluorescent probes are required for high-quality fluorescence imaging, and the rapid development of nanotechnology has led to the emergence of organic dyes with excellent fluorescent properties. Among them, organic fluorescent probes with the advantages of high safety, good biocompatibility, and high optical stability, are more favorable than inorganic fluorescent probes. Therefore, NIR fluorescence imaging assisted with organic fluorescent probes can provide more structural and dynamic information of biological samples to the researchers, which becomes a hot spot in the interdisciplinary research field of optics, chemistry and biomedicine. This review summarizes the application of NIR organic fluorescent probes in cervical cancer imaging. Several typical organic fluorescent probes (such as indocyanine green, heptamethine cyanine dye, rhodamine and polymer fluorescent nanoparticles) assisted NIR fluorescence imaging and their applications in cervical cancer diagnosis were introduced, and the future development and application of these techniques were discussed.
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Female , Humans , Fluorescent Dyes , Nanoparticles , Optical Imaging , Polymers , Uterine Cervical Neoplasms/diagnostic imagingABSTRACT
The preliminary screening of oral cancer mostly depends on the experience of clinicians, The surgical margin of tumor is mostly based on physical examination and preoperative imaging examination. It lacks real-time and objective intraoperative evaluation methods. Indocyanine green (ICG), as a safe and pollution-free organic fluorescent pigments, combined with near-infrared fluorescence imaging can be applied in the screening of early oral cancer, the determination of tumor resection margins, sentinel lymph node biopsy, cervical lymph node dissection, targeted chemotherapy, and other aspects. Near-infrared fluorescence imaging may become a key link in the early diagnosis and accurate treatment for oral cancer in the future.
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Humans , Indocyanine Green , Lymph Nodes , Mouth Neoplasms/therapy , Optical Imaging , Sentinel Lymph Node BiopsyABSTRACT
Near-infrared fluorescence (NIRF) imaging is an emerging technology that aids in real-time intraoperative navigation. NIRF uses fluorescent dyes and probes to obtain real-time anatomical and functional information of blood and lymphatic vasculature and specific tissues during surgery. It can identify small cancerous growths and tumor margins that cannot be normally detected by traditional methods, thus providing the surgeons with a perioperative, anatomical guidance and identification modality to make correct intraoperative decisions. NIRF is promising owing to the following aspects: real-time, sensitive, safe, non-invasive, relatively cheap, and non-ionizing; it has the potential to bring a revolution in the existing surgical techniques. This article comprehensively reviews the basic principles of NIRF imaging technology, the clinical progress in real-time guided tumor resection, sentinel lymph node mapping for cancer staging, and protection of critical anatomical structures during surgery. Furthermore, this review discusses the advantages and limitations of NIRF technology and potential future prospects for its application.
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OBJECTIVE@#To evaluate the clinical application of indocyanine green (ICG) visualization by near infrared fluorescence laparoscopy (NIFL) in complex upper urinary tract reconstructions surgery.@*METHODS@#This was a retrospective study of 7 patients who underwent complex surgeries of ureteral reconstruction between May 2019 and October 2019. There were 6 males and 1 female with the age ranging from 24 to 57 years (median age was 47 years). There were 5 cases of right ureteral strictures, of which 3 were proximal ureteral strictures and 2 were multiple and long ureteral strictures caused by radiotherapy. There were 2 cases of left ureteral strictures, of which 1 was ureteropelvic junction stricture and 1 was proximal ureteral stricture. There were 4 cases of secondary repair operations and 3 cases of primary operations. All the patients underwent laparoscopic surgery via the abdominal approach. ICG was injected into the ureter via nephrostomy tube during the operations, and the diseased ureter was identified by NIFL. Among the patients, 2 cases underwent IUPU (Institute of Urology, Peking University) modified ileal ureter replacement, 2 cases underwent ureteroureterostomy, 2 cases underwent appendiceal onlay flap ureteroplasty, and 1 case underwent lingual mucosa onlay flap ureteroplasty.@*RESULTS@#All the operations were successfully completed without open conversion. The localization and separation of ureteral lesions were completed under NIFL. The mean operative time was 187 (135-300) min. The duration of ureteral separation was 15-27 min, and the mean time was 18 min. The estimated blood loss was 15-200 mL, the mean estimated blood loss was 50 mL. There was one patient with ileal ureter replacement who had fever after surgery and responded well to antibiotics. The mean (range) length of postoperative hospital stay was 7 (6-10) days and no postoperative complications of a high grade (Clavien-Dindo Ⅲ and Ⅳ) occurred. Up to now, the mean follow-up duration was 9 (6-11) months, and no indocyanine green toxicity occurred. All D-J stents and nephrostomy were removed successfully 2 months after the operation. Ultrasound showed no obvious hydronephrosis, and CTU (computed tomography urography) showed that the urinary tract was unobstructed and the kidney function was normal.@*CONCLUSION@#The application of ICG in the complex upper urinary tract reconstructive surgery is a safe and easy method to help surgeon to identify the ureter which may reduce the risk of iatrogenic damage and protect the ureteral blood supply.
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Adult , Female , Humans , Male , Middle Aged , Young Adult , Indocyanine Green , Laparoscopy , Retrospective Studies , Ureter/surgery , Ureteral Obstruction , Urologic Surgical ProceduresABSTRACT
@#Alzheimer′s disease(AD)is a chronic neurodegenerative diseasecommonly seen in the elderlys. Several therapeutic drugs have failed in phase III clinical trials in recent years and there have been no efficient treatment for AD currently. Thus, there has been an urgent need for the effective methods of AD diagnosis at early stage. Developingnear-infrared fluorescentprobes for AD hallmarks detection has been a promising research field. In this review, we summarized a variety of near-infrared fluorescence(NIRF)probes reported in the past decade, which capable of detecting β-amyloid, Tau protein and reactive oxygen species, including their chemical strucutres、optical properties, in vitro and in vivo studies. Furthermore, we alsoraised some new directions for AD diagnosing. We believe that these new directions raised herein will benefit the future development of NIRF probes in the field of AD research.
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BACKGROUND: For the bone-specific imaging, a structure-inherent targeting of bone tissue recently has been reported a new strategy based on incorporation of targeting moieties into the chemical structure of near-infrared (NIR) contrast agents, while conventional methods require covalent conjugation of bone-targeting ligands to NIR contrast agents. This will be a new approach for bone-targeted imaging by using the bifunctional NIR contrast agents. METHODS: The goal of this review is to provide an overview of the recent advances in optical imaging of bone tissue, highlighting the structure-inherent targeting by developing NIR contrast agents without the need for a bone-targeting ligand such as bisphosphonates. RESULTS: A series of iminodiacetated and phosphonated NIR contrast agents for the structure-inherent targeting of bone tissue showed excellent bone-targeting ability in vivo without non-specific binding. Additionally, the phosphonated NIR contrast agents could be useful in the diagnosis of bone metastasis. CONCLUSION: By developing bone-targeted NIR contrast agents, optical imaging of bone tissue makes it very attractive for preclinical studies of bone growth or real-time fluorescence guided surgery resulting in high potential to shift the clinical paradigms.
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Bone and Bones , Bone Development , Contrast Media , Diagnosis , Diphosphonates , Fluorescence , Ligands , Neoplasm Metastasis , Optical Imaging , Surgery, Computer-AssistedABSTRACT
Multimodality optical imaging probes have emerged as powerful tools that improve detection sensitivity and accuracy, important in disease diagnosis and treatment. In this review, we focus on recent developments of optical fluorescence imaging (OFI) probe integration with other imaging modalities such as X-ray computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and photoacoustic imaging (PAI). The imaging technologies are briefly described in order to introduce the strengths and limitations of each techniques and the need for further multimodality optical imaging probe development. The emphasis of this account is placed on how design strategies are currently implemented to afford physicochemically and biologically compatible multimodality optical fluorescence imaging probes. We also present studies that overcame intrinsic disadvantages of each imaging technique by multimodality approach with improved detection sensitivity and accuracy.
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Objective To establish and evaluate a patient-derived orthotopic xenograft ( PDOX ) model of pancreatic cancer. Methods Tissues of patient-derived pancreatic tumor were transplanted into nude mouse pancreas by surgery. The PDOX models were evaluated by the small animal near infrared fluorescence ( NIRF) optical imaging and PET/CT. The traceability of PDOX models was detected by STR technology, and the pathological changes were observed by H&E staining, immunohistochemistry, and serum level of CA19-9 was detected by ELISA. Results Apparent NIRF were observed to be accumulated in pancreatic site by optical imaging system. The location and size of the xenografts tumor were revealed by fluorescence intensity. The PET/CT images with 18F-FDG molecular probe confirmed the tumor's location and size. Ex vivo NIRF imaging of isolated organ further showed the tumor formation. The traceability of PDOX models was 99. 99% with human origin. H&E staining pathology and immunohistochemistry indicated the pancreatic cancer characteristics. The high serum level of ca19-9 confirmed the mice bearing tumor. Conclusions Pancreatic PDOX models are successfully established in this study, and it can be evaluated comprehensively by NIRF optical imaging and PET/CT, providing an appropriate platform for further research of pancreatic cancer.
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Multi-modal fusion molecular imaging technology integrates the advantages of a variety of molecular imaging techniques,and has become a hotspot and trend in the field of molecular imaging. Heptamethine cyanine dye is a class of novel near-infrared fluorescence(NIRF)dye with tumor targeting properties. With its unique optical properties, the dye has broad application prospects in tumor molecular imaging, targeted therapy and drug delivery system. Nano-materials containing heptamethine cyanine dye can be used for NIRF/MRI dual-modal imaging. NIRF/PET dual-modal imaging can be achieved after labeling with nuclides. Conjugated with chemotherapy drugs,targeted delivery of anti-tumor drugs can also be achieved. Complexes of multiple heptamethine cyanine dyes have been used for multi-modal imaging as a new strategy for photothermal therapy,photodynamic therapy and combined treatment of tumors.
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This study investigated the anti-cancer potential of a near-infrared fluorescence (NIRF) molecule conjugated with Cetuximab (Cetuximab-NIRF) in six-week-old female BALB/c athymic (nu+/nu+) nude mice. A431 cells were cultured and injected into the animals to induce solid tumors. Paclitaxel (30 mg/kg body weight (BW)), Cetuximab (1 mg/kg BW), and Cetuximab-NIRF (0.25, 0.5 and 1.0 mg/kg BW) were intraperitoneally injected twice a week into the A431 cell xenografts of the nude mice. Changes in BW, tumor volume and weight, fat and lean mass, and diameter of the peri-tumoral blood vessel were determined after two weeks. Tumor volumes and weights were significantly decreased in the Cetuximab-NIRF (1 mg/kg BW) group compared with the control group (P < 0.001). Lean mass and total body water content were also conspicuously reduced in the Cetuximab-NIRF (1 mg/kg BW) group compared with the vehicle control group. Peri-tumoral blood vessel diameters were very thin in the Cetuximab-NIRF groups compared with those of the paclitaxel group. These results indicate that the conjugation of Cetuximab with NIRF does not affect the anti-cancer potential of Cetuximab and NIRF can be used for molecular imaging in cancer treatments.
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Animals , Female , Humans , Mice , Blood Vessels , Body Water , Body Weight , Cetuximab , Fluorescence , Heterografts , Mice, Nude , Molecular Imaging , Paclitaxel , Tumor Burden , Weights and MeasuresABSTRACT
Objective To study the tumor targeting ability and application of farnesylthiosalicylic Acid (FTS) and heptamethine carbocyanine fluorescent dye-mediated near-infrared imagine in living animals, and confirm the inhibitory effect of this compound on growth of tumor cells.Methods Human breast cancer cell line MCF-7, glioma cell line U251 and prostate cancer cell line PC3 were cultured to logarithmic growth phase, and different concentrations of FTS and FTS-IR783 were added, respectively.We observed the inhibitory effect of those two compounds on the growth of tumor cells.Under fluorescence microscopy, specific accumulation of FTS-IR783 in these tumor cells was observed.The tumor cells (1×106) were transplanted subcutaneously into nude mice.These mice were subjected to intraperitoneal injection of FTS-IR783 (10 nmol/mouse) two weeks later.In the in vivo imaging, near infrared fluorescence signal and tumor volume were measured and their correlation was analyzed.Results Compared with FTS, FTS-IR783 significantly inhibited the growth of MCF-7, U251 and PC3 cells in vitro.FTS-IR783 was specifically uptaken by these three kinds of tumor cells, showing strong near infrared fluorescence in cell agglomerates.After subcutaneous injection of FTS-IR783, the correlation between fluorescence intensity and tumor volume was 0.987, 0.998 and 0.971, respectively.Conclusions The compound of FTS conjugated with near infrared fluorescent dye IR-783 can specifically recognize tumor cells, in both in vitro and in vivo imaging.At the same time, the compound can significantly inhibit the growth of tumor cells, and may be expected to become a new potential targeted drug.
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Objective To study the application of hepatamethine cyanine near-infrared fluorescence (NIRF) dye IR-783 in the mouse models of human liver cancer exenografts, and to analyze the molecular mechanisms of the NIRF dye targeting tumor cells.Methods Luciferase-tagged HepG2 cells were inoculated subcutaneously into the nude mice.We detected the correlation of NIRF intensity and bioluminescence intensity (BIL) in the tumor region.Patient-derived xenograft (PDX) model was established in mouse by subrenal capsular implantation of clinic liver cancer specimen.After injecting the IR-783 dye, the interface between mouse kidney and the xenograft tumors was confirmed by NIRF analysis, and the tumor tissue in kidney was observed by pathology using H&E staining.The expression of CEA, AFP, HIF1α and OATP3A1 in the liver cancer tissue was detected by immunohistochemical staining.The intracellular retention of NIRF dyes was observed under fluorescence microscope after adding Mito Tracker or Lyso Tracker into cultured HepG2 cells.We added IR-783 in a co-culture system of HCCs and normal liver cells to test the specifical identification ability of IR-783 of the liver cancer cells.Results There was a good correlation between NIRF intensity and BIL intensity of the subcutaneous liver cancer xenograft region in nude mice.The margin between the mouse kidney tissue and xenograft tumors was clearly identified by IR-783.Compared with normal kidney tissue, CEA, HIF1α, OATP3A1 and AFP were highly expressed in the tumor region detected by IHC staining.The NIRF dye IR-783 was mainly accumulated in the mitochondria and lysosomes of cancer cells.GFP-tagged HepG2 cells could be recognized directly, whereas red fluorescence was not detected in normal liver cells.Conclusions IR-783 is a novel near-infrared fluorescent dye with tumor targeting and imaging properties.Its targeting ability may be related to the high expression of HIF1α and OATP3A1 in the liver cancer tissue.
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Fluorescence intraoperative cholangiography (IOC) is a potential alternative for identifying anatomical variation and preventing iatrogenic bile duct injuries by using the near-infrared probe indocyanine green (ICG).However,the dynamic process and mechanism of fluorescenceIOC have not been elucidated in previous publications.Herein,the optical properties of the complex of ICG and bile,dynamic fluorescence cholangiography and iatrogenic bile duct injuries were investigated.The emission spectrum of ICG in bile peaked at 844 nm and ICG had higher tissue penetration.Extrahepatic bile ducts could fluoresce 2 min after intravenous injection,and the fluorescence intensity reached a peak at 8 min.Inaddition,biliary dynamics were observed owing to ICG excretion from the bile ducts into the duodenum.Quantitative analysis indicated that ICG-guided fluorescence IOC possessed a high signal to noise ratio compared to the surrounding peripheral tissue and the portal vein.Fluorescence IOC was based on rapid uptake of circulating ICG in plasma by hepatic cells,excretion of ICG into the bile and then its interaction with protein molecules in the bile.Moreover,fluorescence IOC was sensitive to detect bile duct ligation and acute bile duct perforation using ICG in rat models.All of the results indicated that fluorescence IOC using ICG is a valid alternative for the cholangiography of extrahepatic bile ducts and has potential for measurement of biliary dynamics.
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Objective To assess the applicative value of near infrared fluorescence compound PZ -1009 in tumor imaging .Methods Near infrared fluorescence imaging properties of the compound was evaluated in a mouse model of ovarian cancer .The athymic nude mice were inoculated with SKOV -3 ovarian cancer cells and imaged in vivo and ex vivo after injecting PZ -1009 and were performed periodically .Results The tumor loca-tion was clearly imaged after 1 h of injection.The maximum fluorescence intensity was at 6 h time point and there was still a few fluorescent signal in tumors after 48hrs.A professional software was used to measure the intensity including all tumors and normal regions .The results showed that the intensity of tumors was higher than all normal regions in any time points .Conclusion The compound of PZ -1009 can efficiently target tumor sites and has great potential in noninvasive real time early tumor diagnosis .
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Objective To evaluate the effect of near infrared heptamethine cyanine dye IR-783-mediated specific tumor imaging in spontaneous tumor of dogs .Methods IR-783 was intraperitoneally injected to nude mice models of transplanted tumor in a dose of 5μmol/kg.The metabolic time course of IR-783 was detected by in vivo imager .Based on the results of above observation , IR-783 was injected to dogs with spontaneous tumor in a dose of 1.5μmol/kg.The site of intravenous injection was the hind leg .Tumor and peri-tumoral tissues were removed at 5 days after IR-783-injection for fluorescence imaging , pathology and frozen section fluorescence examinations .Results After i.p.IR-783 injection to nude mice models of transplanted tumor , the transplanted tumor tissues of nude mice had stronger specific fluorescence than normal tissues by imaging at 8 days after injection .After i.v.IR-783 injection to four dogs with spontaneous tumor , the fluorescence signal in the tumor tissues was stronger than that in the normal tissues at 5 days after injection .Conclusions Near infrared fluorescent dye IR-783 could be specifically taken up by tumor tissues , and can be used for specific diagnosis of tumor.It has an important clinical application prospect .
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OBJECTIVE: To evaluate the potential and correlation between near-infrared fluorescence (NIRF) imaging using cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles (HGC-Cy5.5) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging of collagen-induced arthritis (CIA). MATERIALS AND METHODS: We used 10 CIA and 3 normal mice. Nine days after the injecting collagen twice, microPET imaging was performed 40 minutes after the intravenous injection of 9.3 MBq 18F-FDG in 200 microL PBS. One day later, NIRF imaging was performed two hours after the intravenous injection of HGC-cy5.5 (5 mg/kg). We assessed the correlation between these two modalities in the knees and ankles of CIA mice. RESULTS: The mean standardized uptake values of 18F-FDG for knees and ankles were 1.68 +/- 0.76 and 0.79 +/- 0.71, respectively, for CIA mice; and 0.57 +/- 0.17 and 0.54 +/- 0.20 respectively for control mice. From the NIRF images, the total photon counts per 30 mm2 for knees and ankles were 2.32 +/- 1.54 x 10(5) and 2.75 +/- 1.51 x 10(5), respectively, for CIA mice, and 1.22 +/- 0.27 x 10(5) and 0.88 +/- 0.24 x 10(5), respectively, for control mice. These two modalities showed a moderate correlation for knees (r = 0.604, p = 0.005) and ankles (r = 0.464, p = 0.039). Moreover, both HGC-Cy5.5 (p = 0.002) and 18F-FDG-PET (p = 0.005) imaging also showed statistically significant differences between CIA and normal mice. CONCLUSION: NIRF imaging using HGC-Cy5.5 was moderately correlated with 18F-FDG-PET imaging in the CIA model. As such, HGC-Cy5.5 imaging can be used for the early detection of rheumatoid arthritis.