Top

Published in:

Open Access 01-04-2004 | Research article

Relationship of cell proliferation (Ki-67) to ^99mTc-(V)DMSA uptake in breast cancer

Authors: Vassilios J Papantoniou, Michael A Souvatzoglou, Varvara J Valotassiou, Androniki N Louvrou, Constantina Ambela, John Koutsikos, Dimitrios Lazaris, Julie K Christodoulidou, Maria G Sotiropoulou, Maria J Melissinou, Aris Perperoglou, Spyridon Tsiouris, Cherry J Zerva

Published in: Breast Cancer Research | Issue 2/2004

Abstract

Introduction

The aim of the present study was to identify the relationships between the uptake of radiotracers – namely pentavalent dimercaptosuccinic acid [(V)DMSA] and sestamibi (MIBI) – and the following parameters in primary breast cancer: steroid receptor concentrations (i.e. estrogen receptor [ER] and progesterone receptor [PR]), Ki-67 expression, tumor size, tumor grade, age, and levels of expression of p53 and c-erbB-2. In addition, by multivariate regression analysis, we further isolated those factors with independent associations with (V)DMSA and/or MIBI uptake in primary breast cancer.

Methods

Thirty-four patients with histologically confirmed breast carcinoma underwent preoperative scintimammography with technetium-99m (^99mTc)-(V)DMSA and/or ^99mTc-MIBI in consecutive sessions 10 and 60 min after administration of 925–1110 MBq of each radiotracer. The tumor-to-background ratio was calculated and correlated with the presence of ER, PR, Ki-67, tumor size, tumor grade, p53, and c-erbB-2. ER, PR, p53, and c-erbB-2 were determined immunohistochemically. The analysis included tumor-to-background ratio of (V)DMSA and MIBI uptake as dependent and all of the other parameters as independent variables.

Results

Correlation was positive between Ki-67 and (V)DMSA (r = 0.37 at 10 min, P = 0.038; r = 0.42 at 60 min, P = 0.018) and inverse between PR and (V)DMSA uptake (r = -0.46 at 10 min, P = 0.010; r = -0.51 at 60 min, P = 0.003). Multivariate regression analysis demonstrated a positive correlation between Ki-67 and (V)DMSA at 60 min (P = 0.045). Ki-67 was not significantly correlated with MIBI uptake, whereas tumor size was positively correlated with MIBI uptake at 60 min both in univariate (r = 0.45, P = 0.027) and multivariate analysis (P = 0.024). Negative correlations were observed between (V)DMSA uptake and ER, as well as between ER/PR and MIBI uptake, but these were not significant.

Conclusion

Ki-67 appears to represent the major independent factor affecting (V)DMSA uptake in breast cancer. Tumor size was the only independent parameter influencing MIBI uptake in breast cancer. (V)DMSA appears to have an advantage over MIBI in that it can be used to visualize tumors with intense proliferative activity, and thus it can identify those tumors that are more aggressive.

Available only for authorised users

Rasey JS, Grierson JR, Wiens LW, Kolb PD, Schwartz JL: Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. J Nucl Med. 2002, 43: 1210-1217.PubMed

Toyohara J, Hayashi A, Sato M, Tanaka H, Haraguchi K, Yoshimura Y, Yonekura Y, Fujubayashi Y: Rationale of 5-¹²⁵I-iodo-4'-thio-2'-deoxyuridine as a potential iodinated proliferation marker. J Nucl Med. 2002, 43: 1218-1226.PubMed

Buck A, Schirrmeister H, Kühn Th, Shen Ch, Kalker Th, Kotzerke J, Dankerl A, Glatting G, Reske S, Mattfeldt T: FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters. Eur J Nucl Med. 2002, 29: 1317-1323. 10.1007/s00259-002-0880-8.CrossRef

Westera G, Gadze A, Horst W: A convenient method for the preparation of ^99mTc(V) dimercaptosuccinic acid (^99mTc(V)-DMSA). Int J Appl Radiat Isot. 1985, 36: 311-312. 10.1016/0020-708X(85)90091-2.CrossRefPubMed

Blower PJ, Singh J, Clarke SEM: The chemical identity of pentavalent ^99mTc-dimercaptosuccinic acid. J Nucl Med. 1991, 32: 845-849.PubMed

Ohta H, Yamamoto K, Endo K, Mori T, Hamanaka D, Shimazu A, Ikekubo K, Makimoto K, Iida Y, Konishi J: A new imaging agent for medullary carcinoma of the thyroid. J Nucl Med. 1984, 25: 323-325.PubMed

Ohta H, Endo K, Fujita T, Nakajima T, Sakahara H, Torizuka K, Shimizu Y, Hata N, Masuda H, Horiuchi K: Imaging of soft tissue tumors with ^99mTc(V)-dimercaptosuccinic acid, a new tumor seeking agent. Clin Nucl Med. 1984, 9: 564-573.CrossRef

Ohta H, Endo K, Fujita T, Konishi J, Torizuka K, Horiuchi K, Yokoyama A: Clinical evaluation of tumor imaging using ^99mTc(V)-dimercaptosuccinic acid, a new tumor seeking agent. Nucl Med Commun. 1988, 9: 105-116.PubMed

Hirano T, Otake H, Yoshida I, Endo K: Primary lung cancer SPECT imaging with pentavalent ^99mTc-DMSA. J Nucl Med. 1995, 36: 202-207.PubMed

10.

Lamki L, Shearer R: Technetium-99m-DMSA uptake by metastatic carcinoma of the prostate. J Nucl Med. 1985, 25: 733-734.

11.

Hirano T, Otake H, Shibasaki T, Tamura M, Endo K: Differentiating histologic malignancy of primary brain tumors: pentavalent Technetium-99m-DMSA. J Nucl Med. 1997, 38: 20-26.PubMed

12.

Hirano T, Otake H, Kazama K, Wakabayashi K, Zama A, Shibasaki T, Tamura M, Endo K: Technetium-99m-(V)-DMSA and Thallium-201 in brain tumor imaging: correlation with histology and malignant grade. J Nucl Med. 1997, 38: 1741-1749.PubMed

13.

Yokoyama A, Saji H: Tumor diagnosis using radioactive metal ions and their complexes. In Metal Ions in Biological Systems. Edited by: Siegel H. 1980, New York: Marcel Dekker, 10: 313-340.

14.

Wulfrank D, Schelstraete K, Small F, Charles F: Analogy between tumor uptake of technetium-99m-(V) dimercaptosuccinic acid (DMSA) and Technetium-99m-MDP. Clin Nucl Med. 1989, 14: 488-593.CrossRef

15.

Palmedo H, Hensel J, Bender H, Wagner U, Bangard M, Bierrsack : ¹⁸F-FDG, ^99mTc-(V)DMSA and ^99mTc-MIBI in an animal breast cancer-model: comparison of tumor-uptake and correlation with scintigraphic and PET-detection [abstract]. Eur J Nucl Med. 2000, 27: 1130-10.1007/s002590050017.CrossRef

16.

Horiuchi K, Saji H, Yokoyama A: Tc(V)-DMS tumor localization mechanism: a pH-sensitive Tc(V)-DMS-enhanced target/non-target ratio by glucose-mediated acidosis. Nucl Med Biol. 1998, 25: 549-555. 10.1016/S0969-8051(98)00012-2.CrossRefPubMed

17.

Papantoniou V, Karganzis P, Stipsanelli A, Arka A, Keramopoulos A, Kostamis P: Technetium-99m (V) dimercaptosuccinic acid [Tc-99m (V) DMSA] in the detection of primary breast cancer. Preliminary results [abstract]. Eur J Nucl Med. 1996, 23: 1216-

18.

Papantoniou V, Stipsanelli A, Arka A, Keramopoulos A, Kostamis P, Michalas S: Comparison of Technetium-99m-[V]-DMSA with Technetium-99m-MDP in diagnosis of breast lesions [abstract]. Eur J Nucl Med. 1998, 25: 1040-

19.

Papantoniou V, Stipsanelli A, Galeros C, Feida E, Kostamis P, Keramopoulos A, Michalas S: Similarity between ^99mTc-V-DMSA and ^99mTc sestamibi in the detection of primary breast cancer. Preliminary results [abstract]. Eur J Nucl Med. 1998, 25: 1040-

20.

Papantoniou V, Stipsaneli A, Christodoulidou J, Louvrou A, Lazaris D, Sotiropoulou M, Papadaki E, Valotassiou V, Pampouras G, Keramopoulos A, Michalas S, Zerva C: ^99mTc-(V)DMSA scintimammography in the assessment of breast lesions. Comparative study with ^99mTc MIBI. Eur J Nucl Med. 2001, 28: 923-928. 10.1007/s002590100545.CrossRefPubMed

21.

Papantoniou V, Christodoulidou J, Papadaki E, Valotassiou V, Souvatzoglou M, Louvrou A, Feida H, Sotiropoulou M, Pampouras G, Michalas S, Zerva C: Uptake and washout of ^99mTc-V-dimercaptosuccinic acid and ^99m-Tc-sestamibi in the assessment of histological type and grade in breast cancer. Nucl Med Com. 2002, 23: 461-467. 10.1097/00006231-200205000-00006.CrossRef

22.

Papantoniou V, Stipsaneli A, Arka A, Louvrou A, Lazaris D, Nakopoulou L, Palikarona P, Keramopoulos A, Michalas S: Immunohistologic assessment of ^99mTc-(V)DMSA and ^99mTc-MIBI uptake in breast cancer [abstract]. Eur J Nucl Med. 1999, 26: 977-

23.

Papantoniou V, Nakopoulou L, Christodoulidou J, Papadaki E, Souvatzoglou M, Stipsaneli A, Lazaris D, Sotiropoulou M, Keramopoulos A, Michalas S, Zerva C: Correlation and multivariate regression analysis between ^99mTc (V)DMSA and ^99mTc MIBI uptake and steroid receptors, proliferation index, tumor size, age, malignant grade, p53, and c-erbB-2 in primary breast cancer [abstract]. Eur J Nucl Med. 2001, 28: 1120-10.1007/s002590100545.CrossRef

24.

Palmedo H, Schomburg A, Grunwald F, Mallmann P, Krebs D, Biersack H: Technetium-99m-MIBI scintimammography for suspicious breast lesions. J Nucl Med. 1996, 37: 626-639.PubMed

25.

Scopinaro F, Schillaci O, Ussof W, Nordling K, Capoferro R, De Vincentis G, Danieli R, Ierardi M, Picardi V, Tavolaro R, Colella AC: A three-center study on the diagnostic accuracy of ^99mTc-MIBI scintimammography. Anticancer Res. 1997, 17: 1631-1634.PubMed

26.

Tavassoli FN: Pathology of the Breast. 1992, Norwalk: Appleton & Lange

27.

Cwikla JB, Buscombe JR, Kolasinska AD, Rarbhaoo SP, Thakrar DS, Hilson AJW: Correlation between uptake of ^99mTc Ses-taMIBI and prognostic factors of breast cancer. Anticancer Res. 1999, 19: 2299-2304.PubMed

28.

Cutrone JA, Yospur LS, Khalkhali I, Tolmos J, Devito A, Diggles L, Vargas MP, Shitabata P, French S: Immunohistologic assessment of technetium-99m-MIBI uptake in benign and malignant breast lesions. J Nucl Med. 1998, 39: 449-453.PubMed

29.

Ohira H, Kubota K, Ohuchi N, Harada Y, Fukuda H, Satomi S: Comparison of intratumoral distribution of ^99mTc-MIBI and deoxyglucose in mouse breast cancer models. J Nucl Med. 2000, 41: 1561-1568.PubMed

30.

Papantoniou V, Sotiropoulou M, Stipsaneli A, Louvrou A, Feda H, Christodoulidou J, Pampouras G, Zerva C, Keramopoulos A, Michalas S: Scintimammographic findings of in situ ductal breast carcinoma in a double-phase study with ^99mTc (V) DMSA and ^99mTc MIBI. Value of ^99mTc (V) DMSA. Clin Nucl Med. 2000, 25: 434-439. 10.1097/00003072-200006000-00009.CrossRefPubMed

31.

Papantoniou V, Stipsanelli A, Christodoulidou J, Papadaki E, Valotassiou V, Louvrou A, Bebi M, Sotiropoulou M, Pampouras G, Keramopoulos A: Scintimammographic detection of ductal in situ carcinomas. Comparative study with ^99mTc(V)DMSA and ^99mTc-MIBI [abstract]. Eur J Nucl Med. 2000, 27: 1129-

32.

Papantoniou V, Sotiropoulou M, Stipsanelli A, Souvatzoglou M, Valotassiou V, Koutsikos I, Louvrou A, Ambela C, Lazaris D, Arka A, Kounadi E, Melissinou M, Zerva C, Michalas S: ^99mTc (V)DMSA breast uptake in usual type hyperplasia (HUT) and apocrine metaplasia (AM) in ralation with cell proliferation index (Ki-67) and the presence of estrogen receptors (ER). Comparative study with ^99mTc-MIBI [abstract]. Eur J Nucl Med. 2003, Suppl 2: S290-

33.

Dawkins HJ, Robbins PD, Smith KL, Sarna M, Harvey JM, Sterrett GF, Papadimitriou JM: What's new in breast cancer: molecular perspectives of cancer development and the role of the oncogene c-erbB-2 in prognosis and disease. Pathol Res Pract. 1993, 189: 1233-1252.CrossRefPubMed

34.

De Potter CR, Schellhom AM: The neu-protein and breast cancer. Virchows Archiv. 1995, 426: 107-115.CrossRefPubMed

Title: Relationship of cell proliferation (Ki-67) to 99mTc-(V)DMSA uptake in breast cancer
Authors: Vassilios J Papantoniou
Michael A Souvatzoglou
Varvara J Valotassiou
Androniki N Louvrou
Constantina Ambela
John Koutsikos
Dimitrios Lazaris
Julie K Christodoulidou
Maria G Sotiropoulou
Maria J Melissinou
Aris Perperoglou
Spyridon Tsiouris
Cherry J Zerva
Publication date: 01-04-2004
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue 2/2004
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/bcr751

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2004

A fly's eye view of tumor progression and metastasis

Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action

Technology review: The use of electrical impedance scanning in the detection of breast cancer

Evolving views of involution

Transforming growth factor-β induces Cdk2 relocalization to the cytoplasm coincident with dephosphorylation of retinoblastoma tumor suppressor protein

Donegan WL, Spratt JS: Cancer of the Breast 5th Edition. London, UK: Elsevier Science Ltd.; 2002. 1050pp

Keynote webinar | Spotlight on antibody–drug conjugates in cancer