in the wavelength range of 400–600 nm. This spectrum region is related to a higher
level of nonspecific background light and limited tissue penetration depth [28]. In
the early years of this millennium, fluorescent imaging for cancer-specific navigation
was successfully used in neurosurgery. Stummer et al. demonstrated that 5-ALA
accumulates as fluorescent protoporphyrin IX in malignant gliomas and helps in
their precise surgical resection. Complete resection of tumor tissue with maximal
preservation of normal surrounding brain tissue significantly improved survival and
life quality of glioblastoma patients (Fig. 2a) [45, 46].
To improve imaging depth with minimal interference of light scattering and tissue
autofluorescence, optical modalities utilize fluorescent emission light in the NIR
wavelengths of 700–900 nm, known as the first near-infrared window (NIR-I).
Furthermore, fluorophores emitting in the range of 1,000–1,700 nm, in the second
near-infrared window (NIR-II), were developed to enhance imaging quality at
increased tissue depth [47, 48]. The NIR spectrum range allows a high ratio of
signal to background in biological tissue and in oncologic imaging yields a high
tumor-to-background ratio [30, 49]. Clinical applications of NIR fluorescence imaging have been demonstrated in sentinel lymph node (SLN) mapping, tumor imaging,
and visualization of vasculature [50].
At present, clinically approved nontargeted contrast agents for image-guided
surgery include ICG and methylene blue (Fig. 2b, c). Their fluorescence emission
is localized within the NIR-I spectrum [28, 39]. Applications of ICG include induced
NIR fluorescence in cancer-related surgery for SLN mapping, intraoperative identification of solid tumors, and angiography during reconstructive surgery [43]
ICG-based imaging agents offer significant improvements during SLN mapping in
prostate, breast, gastric, rectal, and vulvar cancers [51–55].
An integrated diagnostic approach based on premixing of ICG with
99m Tcnanocolloid resulted in an imaging agent that is both radioactive and fluorescent
and enables preoperative and intraoperative SLN imaging in laparoscopic lymph
node dissection. ICG99m Tc-nanocolloid injected into the prostate allowed the location of the pelvic sentinel lymph SLNs to be established preoperatively by SPECT/
CT imaging. During surgery fluorescence was used to visualize previously identified
nodes and improve surgical guidance. Correlation between the radioactive and
fluorescent signal in the removed lymph nodes showed that ICG99m
Tc-nanocolloid
in combination with SPECT/CT and a fluorescence laparoscope can facilitate precise
dissection of SLNs [51].
One of the greatest challenges for prostate cancer management is lymphatic
spread of metastases, giving rise to tumor recurrences. Lymphatic mapping using
radioguidance or fluorescence guidance in surgery via an agent targeting prostatespecific membrane antigen (PSMA) constitutes an alternative to traditional pelvic
lymph node dissection. Preoperative PET imaging with
68 Ga-PSMA tracers was the
most reliable method for identification of lymphatic macrometastases; by comparison, intraoperative lymphatic mapping with ICG99m
Tc-nanocolloid via a fluorescence imaging camera combined with a handheld γ-ray probe was shown to be the
most reliable for identifying micrometastases [56].
212
E. P. Stater et al.
level of nonspecific background light and limited tissue penetration depth [28]. In
the early years of this millennium, fluorescent imaging for cancer-specific navigation
was successfully used in neurosurgery. Stummer et al. demonstrated that 5-ALA
accumulates as fluorescent protoporphyrin IX in malignant gliomas and helps in
their precise surgical resection. Complete resection of tumor tissue with maximal
preservation of normal surrounding brain tissue significantly improved survival and
life quality of glioblastoma patients (Fig. 2a) [45, 46].
To improve imaging depth with minimal interference of light scattering and tissue
autofluorescence, optical modalities utilize fluorescent emission light in the NIR
wavelengths of 700–900 nm, known as the first near-infrared window (NIR-I).
Furthermore, fluorophores emitting in the range of 1,000–1,700 nm, in the second
near-infrared window (NIR-II), were developed to enhance imaging quality at
increased tissue depth [47, 48]. The NIR spectrum range allows a high ratio of
signal to background in biological tissue and in oncologic imaging yields a high
tumor-to-background ratio [30, 49]. Clinical applications of NIR fluorescence imaging have been demonstrated in sentinel lymph node (SLN) mapping, tumor imaging,
and visualization of vasculature [50].
At present, clinically approved nontargeted contrast agents for image-guided
surgery include ICG and methylene blue (Fig. 2b, c). Their fluorescence emission
is localized within the NIR-I spectrum [28, 39]. Applications of ICG include induced
NIR fluorescence in cancer-related surgery for SLN mapping, intraoperative identification of solid tumors, and angiography during reconstructive surgery [43]
ICG-based imaging agents offer significant improvements during SLN mapping in
prostate, breast, gastric, rectal, and vulvar cancers [51–55].
An integrated diagnostic approach based on premixing of ICG with
99m Tcnanocolloid resulted in an imaging agent that is both radioactive and fluorescent
and enables preoperative and intraoperative SLN imaging in laparoscopic lymph
node dissection. ICG99m Tc-nanocolloid injected into the prostate allowed the location of the pelvic sentinel lymph SLNs to be established preoperatively by SPECT/
CT imaging. During surgery fluorescence was used to visualize previously identified
nodes and improve surgical guidance. Correlation between the radioactive and
fluorescent signal in the removed lymph nodes showed that ICG99m
Tc-nanocolloid
in combination with SPECT/CT and a fluorescence laparoscope can facilitate precise
dissection of SLNs [51].
One of the greatest challenges for prostate cancer management is lymphatic
spread of metastases, giving rise to tumor recurrences. Lymphatic mapping using
radioguidance or fluorescence guidance in surgery via an agent targeting prostatespecific membrane antigen (PSMA) constitutes an alternative to traditional pelvic
lymph node dissection. Preoperative PET imaging with
68 Ga-PSMA tracers was the
most reliable method for identification of lymphatic macrometastases; by comparison, intraoperative lymphatic mapping with ICG99m
Tc-nanocolloid via a fluorescence imaging camera combined with a handheld γ-ray probe was shown to be the
most reliable for identifying micrometastases [56].
212
E. P. Stater et al.