Validation of ICG-99mTc-nanoscan as hybrid tracer for sentinel node biopsy

The Sentinel node procedure has been successfully used for decades for the
adequate staging of solid tumors (e.g. head and neck, urological, gynecological
tumors as well as melanoma and breast cancer). This procedure is used in
clinically node negative (cN0) patients. For the SN procedure, a radiotracer is
used, which travels to the first node(s) on which a tumor drains, the SN. Using
lymphoscintigraphy, preoperative mapping of the SN is done. In Europe 99m Tc
Nanocoll is considered the standard for sentinel node biopsy.

As a response to the surgical needs, the SN approach has been enriched with
fluorescence through a collaboration between AvL and LUMC, resulting in the
hybrid tracer indocyanine green (ICG)-99mTc-Nanocoll. This hybrid tracer not
only emits gamma rays but also fluorescence light. This ensures that the
surgeon receives real-time acoustic as well as visual input on the localization
of the SN. Before this tracer was been incorporated to use in daily practice,
the study of Brouwer et al (NL26699.031.09 N09DRF) showed that the behavior of
the hybrid tracer is identical to the golden standard by using preoperative
lymphoscintigraphy. Since then, the SN procedure in head and neck and penile
cancer have been routinely performed with the hybrid tracer Indocyanine Green
(ICG)-99m Tc Nanocoll. After initial in-house production (AvL and LUMC), this
tracer was commercially provided by the radiopharmacy of GE healthcare for
years.

Recently, the raw material Nanocoll is no longer available. 99mTc-Nanocoll has
been replaced by 99mTc-Nanoscan. Chemically, Nanoscan is identical to
Nanocolloid; it concerns both an albumin aggregate (nanocolloid) of a similar
size. The product formulation, however, differs slightly. Despite the same
pharmaceutical specificity and product characteristics, the imaging of both
preparations may differ in details. Something that may impact on the formation
of a hybrid tracer analogue. his is important for the creation of the hybrid
analogue ICG-99mTc-Nanoscan. Nanocoll has not been available since May of this
year, with the hybrid tracer Indocyanine Green (ICG)-99mTc-Nanocoll also
replaced by the analogue nanoscan; Indocyanine Green (ICG)-99mTc-Nanoscan.
Since this replacement, there are already 8 centers that purchase this hybrid
form from the usual supplier, GE Healthcare, for use in routine patient care.

In the past, we have demonstrated that such comparison scan be performed in a
relatively small group of patients whereby the patient acts as its own control.
At first, we used this concept for 99m Tc Nanocoll and ICG 99m Tc Nanocoll
(L26699.031.09 N09DRF) and from this emerged that both tracers revealed a
comparable SN visualization but the last option allowed for additional intra
operative fluorescence imaging. Later on, we used the set up to compare ICG 99m
Tc Nanocol l and 99m Tc SentiScint (NL45185.031.13N13ICG) was performed which
showed that changing the particle size impacted the lymphatic flow but had no
influence on the SN visualization overall.

As no comparison study has been done with the "new" hybrid tracer
(ICG)-99mTc-Nanoscan, we would like to perform a validation of the SN procedure
with ICG-99mTc-Nanoscan. We want to set up this study in analogy with the
comparison study we conducted before the introduction of ICG-99mTc-Nanocolloid
(99mTc-Nanocoll vs. ICG-99mTc-Nanocoll (NL26699.031.09 - N09DRF). In
particular, we want to validate that the hybrid ICG-99m Tc-Nanoscan shows the
same preoperative gland involvement on preoperative lymphoscintigraphy and that
the intraoperative signal intensities remain the same. All this to maintain the
level of current care.

This study has been transitioned to CTIS with ID 2024-519351-28-00 check the CTIS register for the current data.

Cross validation of the hybrid tracer ICG 99 Tc Nanoscan with respect to 99m Tc
Nanoscan for the determination. In particular the intraoperative fluorescence
detection and scintillation detection will be validated for ICG 99 Tc Nanoscan.
In addition, the preoperative lymphoscintigraphic outcome of ICG 99 Tc Nanoscan
will compared to that of the 99m Tc Nanoscan, with patient being his own
control. The validation will be done in 29 patients with melanoma of the head
and neck area or upper part of the trunk, oral malignancies or penile
carcinomas who are scheduled for sentinel node biopsy.

Prospective drug-induced study.

Instead of once, patients are requested to visit the department of Nuclear
Medicine twice. For this study, the patient will receive one additional
injection with ICG-99mTc-Nanoscan. This means that patients will receive one
additional dose of four injections with radioactivity. In addition, one
additional SPECT/CT will be acquired. The total dose of radioactivity is within
the limits that are indicated by the Gezondheidsraad, in the *Normen voor de
toediening van radioactieve stoffen aan vrijwilligers*.

Rarely, nausea, urticaria and anaphylactic reactions (<1/ have been reported
after intravenous injection of 5 25mg ICG. Because of the proposed exclusion
criteria and the intracutaneous injection, these numbers may be assumed to be
lower within this study. In rare case side effects like nausea,
urticaria and anaphylactic reactions are reported with the use of Nanocoll. Up
until now, there has been no reports of these side effects using ICG 99m Tc N
anocoll (N>1500 patients) and because we do not change the amount of ICG (250
mg) we don*t expect this to happen.