Page 37 - ARNM-2-1

Advances in Radiotherapy
& Nuclear Medicine 99m Tc-DOX in multidrug resistance studies

a suitable radionuclide for in vivo imaging, as it is a gamma Lewis lung carcinoma show uptake in the liver and kidneys,
emitter with a short half-life of 6 h. We used a culture of K562 the organs responsible for excretion. Ex vivo studies, on the
and Lucena 1 (a multidrug-resistant cell line) to investigate other hand, provided an avenue for visualizing the 99m Tc-
whether 99m Tc-DOX retains its cytotoxicity and structural DOX uptake in the tumor. In a separate study, we found
characteristics. Tc-DOX, similar to unlabeled DOX, was that breast carcinoma lesions exhibited increased uptake
99]
shown to be cytotoxic to chronic myeloid leukemia cell of 99m Tc-DOX, which was eliminated through renal and
lines (K562) and maintain its capacity as a Pgp substrate hepatic routes. 40
in vitro. Furthermore, the cells were not radiosensitive to
the amount of radionuclide present in the molecule. This 5. Conclusion
could be observed by incubating multidrug-resistant cells
with 99m Tc-DOX and verifying that cytotoxicity was only The present study illustrates the potential of labeling
99m
observed when the drug was internalized and retained DOX with Tc, an approach that may prove to be
inside the cell. conducive to the design of the next-generation DOX
derivatives used in overcoming drug resistance,
DOX labeled with radionuclides have previously been improving intracellular DOX retention, and enhancing
tested to study the characteristics of DOX in tumors. Polyak sustained therapeutic effect. Follow-up studies are
49
50
et al. and Bao et al., using different DOX liposomal warranted to confirm whether 99m Tc-DOX can serve as a
delivery systems, performed a direct radiolabeling of DOX, drug resistance marker.
achieving an efficiency of approximately 70%. In contrast,
we used a non-liposomal DOX, obtaining a 90% efficiency Acknowledgments
by direct labeling.
We appreciate the contribution of Dra. Eliene Oliveira
Another approach to evaluating tumor growth is using Kozlowski kindly prepared the culture of 3LL cells and
radiopharmaceuticals against DNA bases. Sun et al. conducted the tumor induction experiment.
51
imaged DNA synthesis with PET using F-1-(2’-deoxy-2’-
18
fluoro-beta-D-arabinofuranosyl)thymine ( F-FMAU), a Funding
18
pyrimidine analog, which is phosphorylated by thymidine
kinase and incorporated into DNA. Their results This study was supported by grants from Fundação
demonstrated that F-FMAU was selectively retained Carlos Chagas Filho de Amparo à Pesquisa do Estado
18
in the DNA of proliferating cells and was resistant to do Rio de Janeiro (FAPERJ) and Conselho Nacional de
degradation. 51 Desenvolvimento Científico e Tecnológico (CNPq).
Koukourakis et al. labeled liposomal DOX with 99m Tc Conflict of interest
52
and evaluated its uptake in patients with brain tumors. The
radiolabeled DOX accumulation was 13- to 19-fold higher The authors declare they have no competing interests.
in glioblastomas and 7- to 13-fold higher in metastatic
lesions than in the normal brain. Kumar et al. studied Author contributions
53
the DOX labeled with 99m Tc in vitro and in Ehrlich ascites Conceptualization: Vivian M. Rumjanek, Bianca Gutfilen
tumor-bearing mice, and demonstrated the physiological Investigation: All authors
distribution of 99mTc-DOX in kidneys and liver. The Methodology: All authors
tumor had a focused uptake of the radiopharmaceutical at Writing – original draft: All authors
1.5 h up to 4 h. Bao et al. demonstrated that the labeled Writing – review & editing: Bianca Gutfilen, Sergio Augusto
50
pegylated DOX in normal rats had a slow blood clearance Lopes de Souza, Vivian M. Rumjanek
and a high uptake in the bowel and surrounding tissues.
In another study, Yang et al. investigated the behavior of Ethics approval and consent to participate
54
DOX liposomes labeled with 111] In after their intravenous
administration to intracranial human glioblastoma tumor- National Cancer Institute, Ministry of Health, Brazil.
bearing mice suffering blood–brain barrier disruption Consent for publication
induced by focused ultrasound.
In this study, DOX was labeled using a direct method, Not applicable.
an approach that allows for high labeling efficiencies. It Availability of data
is important to point out that there is a difference in the
biodistribution of 99m Tc and 99m Tc-DOX. 99m Tc-DOX is Data are available from the corresponding author on
uptaken by the kidneys in normal mice, while mice with reasonable request.

Volume 2 Issue 1 (2024) 6 https://doi.org/10.36922/arnm.2822