Pentavalent technetium-99m dimercaptosuccinic acid [99mTc-(V)DMSA] brain scintitomography—a plausible non-invasive depicter of glioblastoma proliferation and therapy response

Abstract

The biological behavior and prognosis of gliomas depend largely on cellular proliferation, resistance to chemotherapy, and metastatic potential. Proliferative propensity has significant implications on patient management but its assessment requires tissue sampling; the non-invasive estimation of brain tumor proliferation represents therefore a major goal. Pentavalent technetium-99 m dimercapto-succinic acid [99m Tc-(V)DMSA] is a tumor-seeking radiotracer displaying affinity for gliomas; its intracellular accumulation is directly linked to cell proliferation. We performed a tomographic 99m Tc-(V)DMSA brain scan in a 35-year-old male baring a recurrent glioblastoma multiforme, to depict its proliferative disposition. The patient had been diagnosed 14 months earlier and had been submitted to surgery, followed by adjuvant radiotherapy and temozolomide-based chemotherapy. On clinical suspicion of recurrence 5 months later, magnetic resonance imaging (MRI) revealed a lesion at the site of preceded surgery, which was treated by imatinib mesylate. No improvement was ascertained the following months and radiographic assessment verified tumor progression. Scintitomography revealed avid radiotracer uptake in the entirety of the lesion (the distribution of radioactivity closely conforming to the morphological tumor boundaries), an indication that the neoplasm demonstrated no substantial proliferation decline in response to imatinib. The patient deceased a few weeks later. Mounting in vivo and in vitro evidence indicates that 99m Tc-(V)DMSA is a credible non-invasive proliferation depicter, its cellular accumulation linked closely to phosphate uptake and kinase pathway activation. A potential role in patient management, prognosis estimation, and therapy response monitoring could occur for this tracer.

Scintimammography - Molecular Imaging: Value and New Perspectives with 99mTc(V)-DMSA

“…D. Likewise, the inhomogeneous diffuse uptake area on the normal right breast becomes clearer and expands over time. No biopsy for histologic confirmation was performed on this breast; nonetheless, based on our experience from similar histologically-verified scintimammographic patterns, the finding is suspicious of representing a widespread pre-invasive lesion (DCIS and/or epithelial hyperplasia) [Papantoniou et al, 2007].…”

“…Specifically, 99m Tc(V)-DMSA scintimammography in combination with mammography may substantially contribute toward the visualization of these lesions [Papantoniou et al -2007[Papantoniou et al , 2010[Papantoniou et al , 2011.…”

“…99m Tc(V)-DMSA is a well-known tumor-seeking radiotracer with affinity for neuroendocrine and soft tissue tumors, such as medullary thyroid carcinoma and lung, breast, brain, and metastatic bone lesions [Ohta et al, 1984, Babbar et al, 1991, Kashyap et al, 1992, Hirano et al, 1995, Atasever et al, 1997, Lam et al, 1997, Kiratli et al, 1998, Papantoniou et al, 2002, 2010, Denoyer et al, 2004, Tsiouris et al, 2007, Al-Saeedi, 2007. These tumor-seeking properties have lead to the use of 99m Tc(V)-DMSA in scintimammographic studies.…”

“…Based on in vivo scintigraphic studies, we advocated that its cellular uptake mechanism is closely related to cellular proliferation, as expressed by the Ki-67 immunohistologic index [Papantoniou et al, 2004[Papantoniou et al, -2006 and at the same time is independent from estrogen receptor (ER) status [Babbar et al, 1991, Kashyap et al, 1992. It has been further demonstrated that the uptake of 99m Tc(V)-DMSA is related to cell proliferation, focal adhesion kinase (FAK) activation, neo-angiogenesis and overexpression of several growth factors, including CGRP and platelet-derived growth factor (PDGF) [Papantoniou et al, -2007[Papantoniou et al, , 2010[Papantoniou et al, , 2011. Denoyer and colleagues elucidated the exact mechanisms; notably, the tracer reflects phosphate ion (Pi) transport and metabolism, entering cancer cells specifically via the type III Na/Pi co-transporter, this uptake being driven by the cellular levels of phosphorylated (i.e.…”

Metabolic Imaging of Brain Tumor by 99mTc-Tetrofosmin Scintitomography

“…With regards to labeled amino acid SPECT, 123 I-IMT was similarly reported to correlate with Ki-67 expression (Kuwert et al, 1997). Finally, pentavalent 99m Tcdimercapto-succinic acid ( 99m Tc-[V]DMSA) is another tumor-seeking tracer whose proliferative imaging potential in gliomas has been suggested in vitro and sporadically reported in vivo (Denoyer et al, 2005;Tsiouris et al, 2007).…”