a drug already approved found to make chemotherapy more effectve&protects normalcells

[Lani]

Due to all the time and money required to develop new drugs, vaccines and other therapies the greatest hope for more effective treatments in the shortterm is the utilization of drugs already available in new ways (off label, until they get approved for these uses)

A drug commonly given as a contrast agent with MRI scans (not CT scans) seems to fit this description. Look for clinical trials to start with this as they must still determine the most effective and safe dose, and check its safety and interactions when given more often (one doesn't get MRIs daily or even weekly)

The good news:

this should cross the blood-brain barrier or it wouldn't be so useful for MRIs

[Lani]

even though it is an MRI contrast agent it is a very specialized contrast agent for looking a liver lesions . Here is a paper describing the usefulness of the agent in determining if liver lesions are resectable (another practical use of this agent in her2neu patients?) After "googling" I found the compound's molecular size and will try to look up if this means it can cross the blood-brain barrier:

Clinical and Cost Effectiveness of a New Hepatocellular MRI Contrast Agent, Mangafodipir Trisodium, in the Preoperative Assessment of Liver Resectability

Gary N. Mann, MD, Howard F. Marx, MD, Lily L. Lai, MD and Lawrence D. Wagman, MD
From the Department of General Oncologic Surgery (GNM, LLL, LDW) and Division of Radiology (HFM), City of Hope National Medical Center, Duarte, CA 91010.

Correspondence: Address correspondence and reprint requests to: Gary N. Mann, MD, Department of Surgery, Section of Surgical Oncology, University of Washington, 1959 NE Pacific Street, P.O. Box 356410, Seattle, WA 98195; Fax: 206-543-8136; E-mail: gnmann@ u.washington.edu.

Background: Improved preoperative assessment of focal liver disease and tumors could have a potentially significant impact on their treatment. Mangafodipir trisodium (Teslascan; Nycomed Amersham Imaging, Little Chalfont, UK) is a new hepatocellular contrast agent for use with state-of-the-art MR imaging that, in early reports, is accurate in detection and characterization of liver lesions.

Methods: Records and diagnostic images of all patients undergoing enhanced Teslascan MRI (T-MRI) at our institution were reviewed. We assessed the relative sensitivities of contrast-enhanced CT scan (CECT) and T-MRI in detecting lesions, as well as the impact of T-MRI in the decision to operate or not on patients. In those patients taken to surgery, the correlation between T-MRI and intraoperative palpation and intraoperative ultrasound (IOUS) was determined.

Results: Fifty-four patients were noted on CECT to have focal liver lesions and subsequently underwent imaging with T-MRI. The T-MRI correlated with CT findings in 22 patients (41%), upstaged the liver disease in 26, and demonstrated fewer lesions in 6. Only 43 patients were considered operative candidates and T-MRI influenced the operative decision in 32 patients (74%), dissuading operative intervention in 14. In the 25 patients without clear preoperative evidence of unresectability who were taken to the operating room, T-MRI correlated with findings of intraoperative palpation in 19 (76%). In the 20 patients who underwent IOUS, T-MRI correlated with IOUS in 14 patients (70%). IOUS detected an additional nine lesions, all of which were <1 cm. Seventeen patients underwent resection and/or ablation of their liver lesions. Compared with pathology, sensitivities of CECT, T-MRI, and intraoperative evaluation were 61%, 83%, and 93%, respectively. T-MRI failed to predict hepatic-specific unresectability in only one of eight patients, the other seven having extrahepatic disease.

Conclusions: These findings suggest that T-MRI is more sensitive than CECT in the preoperative predicting of the resectability of hepatic lesions. Despite T-MRI accurately correlating with intraoperative surgical findings, IOUS should be performed on all patients prior to a final decision to resect or ablate a focal liver lesion.

[Lani]

even though it is an MRI contrast agent it is a very specialized contrast agent for looking a liver lesions . Here is a paper describing the usefulness of the agent in determining if liver lesions are resectable (another practical use of this agent in her2neu patients?) After "googling" I found the compound's molecular size and will try to look up if this means it can cross the blood-brain barrier:

Clinical and Cost Effectiveness of a New Hepatocellular MRI Contrast Agent, Mangafodipir Trisodium, in the Preoperative Assessment of Liver Resectability

Gary N. Mann, MD, Howard F. Marx, MD, Lily L. Lai, MD and Lawrence D. Wagman, MD
From the Department of General Oncologic Surgery (GNM, LLL, LDW) and Division of Radiology (HFM), City of Hope National Medical Center, Duarte, CA 91010.

Correspondence: Address correspondence and reprint requests to: Gary N. Mann, MD, Department of Surgery, Section of Surgical Oncology, University of Washington, 1959 NE Pacific Street, P.O. Box 356410, Seattle, WA 98195; Fax: 206-543-8136; E-mail: gnmann@ u.washington.edu.

Background: Improved preoperative assessment of focal liver disease and tumors could have a potentially significant impact on their treatment. Mangafodipir trisodium (Teslascan; Nycomed Amersham Imaging, Little Chalfont, UK) is a new hepatocellular contrast agent for use with state-of-the-art MR imaging that, in early reports, is accurate in detection and characterization of liver lesions.

Methods: Records and diagnostic images of all patients undergoing enhanced Teslascan MRI (T-MRI) at our institution were reviewed. We assessed the relative sensitivities of contrast-enhanced CT scan (CECT) and T-MRI in detecting lesions, as well as the impact of T-MRI in the decision to operate or not on patients. In those patients taken to surgery, the correlation between T-MRI and intraoperative palpation and intraoperative ultrasound (IOUS) was determined.

Results: Fifty-four patients were noted on CECT to have focal liver lesions and subsequently underwent imaging with T-MRI. The T-MRI correlated with CT findings in 22 patients (41%), upstaged the liver disease in 26, and demonstrated fewer lesions in 6. Only 43 patients were considered operative candidates and T-MRI influenced the operative decision in 32 patients (74%), dissuading operative intervention in 14. In the 25 patients without clear preoperative evidence of unresectability who were taken to the operating room, T-MRI correlated with findings of intraoperative palpation in 19 (76%). In the 20 patients who underwent IOUS, T-MRI correlated with IOUS in 14 patients (70%). IOUS detected an additional nine lesions, all of which were <1 cm. Seventeen patients underwent resection and/or ablation of their liver lesions. Compared with pathology, sensitivities of CECT, T-MRI, and intraoperative evaluation were 61%, 83%, and 93%, respectively. T-MRI failed to predict hepatic-specific unresectability in only one of eight patients, the other seven having extrahepatic disease.

Conclusions: These findings suggest that T-MRI is more sensitive than CECT in the preoperative predicting of the resectability of hepatic lesions. Despite T-MRI accurately correlating with intraoperative surgical findings, IOUS should be performed on all patients prior to a final decision to resect or ablate a focal liver lesion.

[Lani]

can only find molecular weight (770) not size but read it is a chelated metal which normally are too big to diffuse out of the circulation much and therefore end up in the liver for processing. Seems rather unlikely (even though I could not find the molecular size so far) that it would cross the blood-brain barrier (molecules <500 Daltons can do so reliably IF they meet other characteristics regarding their shape, lipophilicity (literally love/like of fat, practically how well it mixes with fat --think of oil and vinegar salad dressing!) Haven't reallyhad to use my biochemistry-course gained knowledge of molecular size,weight and lipophobic/lipophilic properties for 30 years--amazing some of it is still in the old lipophylic brain! (I am sure RB has something to say about that)

Hope some of this helped...

[al from Canada]

Hi Lani,

I'v been in a serious fog since Linda passed. As a result, I'm not sure where this is going. Can you give us all a readers digest version please.
Thanks in advance,
Al

[Chelee]

I don't know if its just me...but this stuff seems hard to fully understand at times for ME. (Maybe its easy for others...but I get lost no matter how hard I try.) I get the drift I think? Then you ADD my chemo brain to this...and I am in a complete fog. lol
I wish there was a summary that was easier to understand as I ALWAYS am very interested in these updated articles...I just can't fully comperhend (sp) it?

Chelee

[Lani]

So sorry! I went back to see what you didn't understand and I see that I negligently omitted to post the article in the first place! It was from the BBC and well-written so I couldn't understand why everyone was so puzzled! And I continued to waltz around the omission by adding more and more info when I forgot to post the name of the agent and how it seems to have two helpful effects--making chemo more efficacious and protecting normal cells from the chemo. My deepest apologies for my lapse, aka a "strokette":
Scan drug 'boosts cancer therapy'

Chemotherapy can damage healthy cells
A drug used to help doctors interpret medical scans may also help to boost the potency of anti-cancer therapies, research suggests.
Mangafodipir is used as a contrast agent in hi-tech magnetic resonance imaging (MRI).

French researchers found it increased the cancer-killing ability of some chemotherapy drugs, while at the same time protecting normal cells.

Details are published in the Journal of the National Cancer Institute.


We welcome the discovery that this well-understood and tolerated chemical can increase the effectiveness of conventional chemotherapy
Henry Scowcroft

Many anti-cancer drugs work by increasing the levels of hydrogen peroxide in tumour cells.

Tumour cells are particularly sensitive to the chemical, and die as a result.

However, certain enzymes in the body can work to protect cells from this kind of damage, rendering certain cancer drugs less effective.

In addition, the drugs are toxic to normal cells.

Double effect

Mangafodipir was found to help promote the production of hydrogen peroxide while at the same time, through different biological mechanisms, protecting healthy cells from damage.

A team from the Groupe hospitalier Cochin-Saint Vincent de Paul in Paris carried out tests on tumour cells and white blood cells taken from cancer patients, and white blood cells taken from healthy patients.

Each type of cell was exposed to three chemotherapy drugs - paclitaxel, oxaliplatin, and 5-fluorouracil - in the presence and absence of mangafodipir.

Mangafodipir was found to protect the white blood cells taken from both the healthy volunteers and the cancer patients.

The researchers also studied the effects of mangafodipir on mice with colon cancer who were being treated with paclitaxel.

Tolerated chemical

They found the drug protected the animals from infection which could compromise their immune system, and seemed to increase the cancer-killing potency of paclitaxel.

Henry Scowcroft, cancer information officer at Cancer Research UK, said: "Mangafodipir was developed in the early nineties and has a good track record in cancer diagnosis.

"We welcome the discovery that this well-understood and tolerated chemical can increase the effectiveness of conventional chemotherapy.

"These exciting preliminary results now need to be followed up in further trials, to make sure that the chemical is as safe when used for treating cancers as it is for helping detect them."

[al from Canada]

Thanks Lani, that's what we look for in some of our suppliments:sensitizing agents that augment the chemo action and are also protectants of normal cells.al