Assessment of Tracer 99mTc(V)-DMSA Uptake as a Measure of Tumor Cell Proliferation In Vitro

Fatma Al-Saeedi ,Princy M Mathew,Yunus A Luqmani

doi:10.1371/journal.pone.0054361

Abstract

PurposeTo examine whether 99mTc(V)-DMSA could be used as a non-invasive measure of cancer cell proliferation.MethodsHuman breast cancer MCF-7, MDA-MB-231 and pII, and prostate cancer PC-3 cell lines were grown to 30, 50 and 100% confluency and pulsed with 99mTc(V)-DMSA in media for 60 min at 37°C. DNA synthesis was analysed by quantification of the S phase using flow cytometry, [methyl-3H]thymidine incorporation and expression of proliferation markers PCNA and Ki-67 using realtime PCR. One way ANOVA was used to compare groups.ResultsIn all cell lines rates of 99mTc(V)-DMSA uptake were inversely related to cell density. This was paralleled by similar trends in S phase proportions, [methyl-3H]thymidine incorporation and expression of PCNA and Ki-67.ConclusionRates of 99mTc(V)-DMSA uptake into different types of tumour cells correlate well with cell density that is useful as a non-invasive measure of tumour cellular proliferation in vivo.

Highlights

The ability to non-invasively detect and image cell growth and proliferation throughout the body has long been recognised to be of significant value in the diagnosis, staging and treatment of cancer
Radionuclide, 99mTc, was obtained from a molybdenum-99technetium-99m (99Mo-99mTc) generator located in the Clinical Nuclear Medicine Department of Mubarak Al Kabeer Hospital, Kuwait. [Methyl-3H]thymidine was obtained from Amersham. 2-[fluorine-18]Fluoro-2-deoxy-Dglucose (18F-FDG) was obtained from Kuwait Cancer Center (Kuwait)
Uptake of 99mTc(V)-dimercaptosuccinic acid (DMSA) Initial experiments were conducted with MCF-7 cells to optimize conditions

Summary

Introduction

The ability to non-invasively detect and image cell growth and proliferation throughout the body has long been recognised to be of significant value in the diagnosis, staging and treatment of cancer. The expansion of a tumour mass is directly related to its growth fraction, which can be assessed by measuring DNA synthesis by following incorporation of [3H] or [14C] labelled thymidine. This is acceptable for in vitro model systems and in animals but as long lived beta emitters, neither radionuclide is suitable for imaging in humans. For several decades the most commonly used PET tracer has been the cyclotron produced 2-[fluorine-18]Fluoro-2-deoxy-D-glucose (18FFDG) This is neither cell specific nor very appropriate for measurement of cell proliferation, besides which it has a short half-life of less than 2 h. There are some practical drawbacks of 18F-FLT for identifying sites of proliferative activity or malignancy in the liver and bone marrow due to the presence of high background radioactivity, and interference with pelvic lesions due to its significant excretion into the urinary bladder [8,9,10,11]

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