ISSN 0003-6838, Applied Biochemistry and Microbiology, 2017, Vol. 53, No. 8, pp. 823–826. © Pleiades Publishing, Inc., 2017.
Original Russian Text © B.M. Manuilov, A.V. Ermakov, 2016, published in Biotekhnologiya, 2016, Vol. 32, No. 3, pp. 78–83.
Preparation and Properties of Nanocolloidal Rhenium Sulfide
Solution for Lymphoscintigraphic Methods
of Micrometastase Examination
B. M. Manuilov
* and A. V. Ermakov
Pharmaceutical Research and Production Enterprise Saluta-M, Istra, Moscow oblast, 143500 Russia
Hertzen Moscow Cancer Research Institute, National Medical Research Radiological Center,
Ministry of Health of the Russian Federation, Moscow, 125284 Russia
Received May 12, 2016
Abstract⎯A method for the preparation of a nanocolloidal solution of rhenium sulfide is proposed. It
includes the following stages: interaction of ammonium perrhenate and sodium thiosulfate in an aqueous
solution of gelatin in an acidic medium with heating to 70–80°C; neutralization to pH 7.0; dialysis against
saline; desalination and concentrating by ultrafiltration. The resulting colloidal solution contains 85% of par-
ticles with an optimal size of 80–100 nm and can be used as a diagnostic tool for lymphoscintigraphy of sen-
tinel lymph nodes in patients with cancer and other diseases.
Keywords: diagnostic tool, lymphoscintigraphy, nanocolloidal solution
Lymphoscintigraphic research methods have
recently been used to diagnose the condition of the
lymphatic system. Lymphoscintigraphy was intro-
duced into surgical practice as the main method for
studying the features of lymphatic drainage of tumors
. Lymphoscintigraphy allows the diagnosis of met-
astatic lesions of lymph nodes, determination of the
causes of edema, and assessment of lymphatic drain-
age disorders in various diseases [2–4].
The detection of micrometastases in the lymph
nodes by methods of functional radionuclide lympho-
scintigraphy makes it possible to correct surgical treat-
ment and perform organ-preserving surgeries [5–7].
To achieve the highest efficiency, the diagnostic
tool should be a colloidal system with a particle size
from 80 to 100 nm, which can flow through the phys-
iological capillaries into the lymph vessels and lymph
nodes after subcutaneous injection in a neoplasm .
At present, a number of agents containing colloidal
solution of rhenium sulfide labeled with technetium-
99 isotope (
Tc) are used globally in practice for lym-
phoscintigraphy. These agents include Nanocis
(France), Nanotop (Germany), Nanocoll (Italy), and
Koren 99mTc (Russia). The radioactive technetium
isotope has a very short half-life (6 h) and low cost,
which promotes the widespread use of radioisotope
studies using this component [9–11].
However, the listed foreign lymphotropic agents
are difficult to access for wide application, and the
Russian agent Koren 99mTc has a significant draw-
back: it can be captured by the reticuloendothelial system
cells and excreted in the lymphatic bed only after it forms
a colloid opsonium complex with blood proteins.
In this regard, the creation of a domestic nanocol-
loid diagnostic lymphotropic agent that will possess all
of the necessary properties (including the required
nanoparticle sizes of 80–100 nm) and be available for
widespread use and convenient in application is a very
urgent challenge for practical medicine.
In the work, we used Russian reagents of analytical
and reagent grades. Desalination experiments were
carried out on a column (1.5 × 30 cm) filled with Sep-
hadex G-25sf (Pharmacia, Sweden); a Uvicord S11
UV detector (Pharmacia LKB, Sweden) with a wave-
length of 280 nm was used.
Preparation of the colloidal solution was carried
out as follows: 100 mL of a 1% solution of gelatin in
0.4N HCl and 30–40 mg of ammonium perrhenate
were placed in a glass thermostated reactor equipped
with a stirring system; the resulting solution was
heated to 40°C under stirring; an aqueous solution of
400 mg of sodium thiosulfate (100 mg/mL) was added
portion-wise by 0.1 mL; and the temperature of the