A blog reader (thanks!) gave me the link to this not-so-shocking-anymore (!) article about Omniscan, a gadolinium-based contrast agent that often gets injected into the veins of patients undergoing MRIs, including myeloma patients: http://goo.gl/scjaG. (I decided to post the link today because it’s veeeeeeery closely related to the post I published two days ago on “evidence-based medicine.”)
Do you remember my posts on gadolinium? If not, just click here: http://goo.gl/VeqeB
In a nutshell, gadolinium is a toxic metal that makes myeloma cells proliferate like crazy. And now it appears that “unfavorable data” regarding Omniscan was supposed to have been burned in 1994 (!). Luckily, it wasn’t, thanks to the researcher who “reached troubling findings”…Don’t miss the part about the 25% of missing gadolinium…eeeek.
Well, as I mentioned in my previous, related post, in my opinion…
WE NEED TO KNOW ABOUT THIS STUFF.
(Sheesh…)
UPDATE: thanks to a query by a member of the Italian MGUS support group on Facebook (of which I am co-administrator), I found this abstract, titled “Nephrogenic systemic fibrosis: the first Italian gadolinium-proven case” http://goo.gl/qTwvH Eeeek.
from https://ash.confex.com/ash/2009/webprogram/Paper17203.html
“1809 Gadolinium Containing Contrast Agent Promotes Multiple Myeloma Cell Growth: Implication for Clinical Use of MRI in Myeloma
Oral and Poster Abstracts
Poster Session: Myeloma – Biology and Pathophysiology, excluding Therapy Poster I
Saturday, December 5, 2009, 5:30 PM-7:30 PM
Hall E (Ernest N. Morial Convention Center)
Poster Board I-831
Mariateresa Fulciniti, PhD1*, Swaminathan Sundararaman2*, Puru Nanjappa, MS1*, Samir B Amin, MBBS3*, Prajwal Chevireddy4*, Neriman Gokden, PhD5*, Kim Hiatt2*, Whitney High6*, Masood A Shammas, PhD7*, Rao Prabhala, PhD8, Teru Hideshima, M.D., Ph.D.9, Pierfrancesco Tassone10*, Kenneth C. Anderson, MD11, Sudhir V. Shah2* and Nikhil C. Munshi, MD12
1Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
2University of Arkansas, Little Rock, AR
3Medical Oncology, Dana-Farber Cancer Institute, Boston VA Healthcare System, Harvard Medical School, Boston, MA
4University of Arkansas, Arkansas, AR
5Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR
6Denver
7VA Boston Health Care System/ DFCI, West Roxbury, MA
8VA Boston Health Care System/ DFCI/HMS, West Roxbury, MA
9Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
10University Magna Graecia, Catanzaro, Italy
11Dana-Farber Cancer Institute, Boston, MA
12Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston VA Cancer Healthcare System, Boston, MA
Bone marrow infiltration by myeloma cells and osteolytic bone lesions are the major features of Multiple Myeloma. Magnetic Resonance Imaging (MRI) has been used in MM not only to image bone marrow (BM) and to identify lytic bone disease but to also evaluate therapeutic response and prognosis. Gadolinium (Gd)-based contrast agents are frequently used to enhance MRI resolution. We evaluated effect of the most common Gd-containing agent, Omniscan, on myeloma cells. We observed that Omniscan induced both time and dose dependent MM cell growth in vitro (8-20 fold increase relative to control). Importantly, the presence of BMSC enhanced the effect of Omniscan on growth of both MM cell lines and primary MM cells. However, Omniscan was not able to overcome cytotoxic effects of conventional and novel agents in MM. This growth promoting effects were not observed on normal BM stromal cells. Evaluating the molecular mechanism of action of Omniscan on MM cells, we observed time dependent ERK1/2 phosphorylation as well as reversal of growth promoting effects of Omniscan by specific inhibition of ERK signaling; however, Omniscan had no effect on STAT3 and AKT signaling pathways. Next, we investigated in vivo effect of Omniscan in a murine xenograft model of MM. Following detection of tumor, mice were treated with either iv Omniscan or PBS. Treatment with Omniscan significantly induced MM tumor growth compared to control mice (1042 ±243 mm3 vs 502 ±137 mm3 respectively; p=0.0001). Finally in autopsies in 8 MM patients with repeated exposure to Omniscan, we quantified gadolinium in various tissues using Inductively-coupled mass spectrometry. We observed massive quantities of gadolinium accumulation in tissues of these MM patients regardless of their renal function. These results, confirming both in vitro and in vivo growth promoting effects of Gd-containing contrast agent on MM, suggest the need for further analysis of the mechanism of its action on myeloma cells and careful analysis of its clinical impact in MM patients undergoing MRI evaluation.
Disclosures: No relevant conflicts of interest to declare.
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