|
04-25-2011, 02:14 PM
|
#1
|
Senior Member
Join Date: Mar 2006
Posts: 4,778
|
GETTING DRUGS THROUGH THE BLOOD-BRAIN BARRIER 2 treat brain mets, tumors w aid of US
US=ultrasound
Ultrasound Crosses Last Frontier: The Blood-Brain Barrier
— A novel ultrasound device has been shown to enhance drug distribution in the rat brain, owing to its ability to cross the blood–brain barrier (BBB). This and a study that investigated the mechanism of the ultrasound-related opening of pores in the BBB were reported here at the American Institute of Ultrasound in Medicine 2011 Annual Convention.
In the first proof-of-concept presentation, George K. Lewis MS, a PhD graduate student at Cornell University in Ithaca, New York, described an experiment to determine the efficacy and safety of ultrasound-enhanced drug distribution in the rat brain.
"The purpose here is to address the problem of treating glioblastomas — high-grade forms of brain cancer that have very poor outcomes," Mr. Lewis said. Few drugs have been found to be effective in this cancer type, he added, if for no other reason than the inability of systemic administration to gain access to the tumor because of the BBB.
For operable tumors, the current standard of treatment is removal of the tumor. However, because tumor margins for surgical purposes must remain necessarily limited in the central nervous system (CNS), tumor cells inevitably remain on the periphery of the tumor site. Thus, direct exposure to chemotherapy follows the surgical procedure.
"This is done with either implantation of encapsulated, drug-laden wafers (i.e., polifeprosan 20 with carmustine implant)," said Mr. Lewis, "or convection-enhanced delivery (CED), where you actually insert a needle into the region and infuse [the drug] under high pressure to cover the area with the drug." With either method, however, drug penetration is limited.
"Our approach is to infuse the drug, and then use 2 different methods to distribute it." The first approach uses a low-profile transducer cannula assembly, and the second uses a novel construction — a so-called time-reversal acoustics drug delivery cannula. "It's not as dramatic as plane wave, but it's more tightly focused," said Mr. Lewis. These methods were previously shown to have promise in ex vivo investigations.
The current study exposed anesthetized rats with craniotomies to a tracer dye, using both methods described above, both with and without stabilized microbubbles. After animal sacrifice, frozen sectioning and histology were performed for a 3-dimensional reconstruction to measure the infusion volume and to assess possible tissue damage to the brain.
Results showed that the application of ultrasound CED did indeed enhance tracer distribution, compared with control; further, this was accomplished without any apparent tissue damage. "We actually got a 2 to 3 times increase in the distribution volume covering the whole caudate region," said Mr. Lewis, however, "what was surprising to us was that when you combined CED and ultrasound with microbubbles, we did not see this effect. We thought they would actually oscillate in the field and enhance the penetration of the tracer, but that wasn't the case."
Mr. Lewis and colleagues surmise that the microbubbles formed were on a scale much larger than CNS endothelial pores, and that "we might have been clogging it up."
Given these results, the Cornell scientist is looking to repeat this investigation with larger animals.
Getting at the Mechanism of Microbubble Action
Delving into the basic science behind microbubble activity in the CNS and permeability of the BBB, Yao-Sheng Tung, MS, from the Department of Biomedical Engineering at Columbia University in New York City, reported on his work with microbubbles and focused ultrasound.
Mr. Tung and colleagues used a cylindrically focused hydrophone, confocal with the focused ultrasound transducer, as a passive cavitation detector to identify the threshold of inertial cavitation in the presence of Definity (Perflutren Lipid Microsphere) microbubbles.
Results showed that the inertial cavitation response could be detected transcranially during the BBB opening, and that the inertial cavitation pressure threshold lay at 0.45 MPa. "However, the BBB was opened at 0.30 MPa, so the BBB can be opened without requiring inertial cavitation."
Importantly, these activities did not cause any tissue damage, Mr. Tung added.
Dr. Lewis has been granted a US provisional patent (No. 61311064) for technology related to this study. Dr. Tung has disclosed no relevant financial relationships.
American Institute of Ultrasound in Medicine (AIUM) 2011 Annual Convention: Abstracts 989301 and 990294. Presented April 17, 2011.
|
|
|
04-25-2011, 02:29 PM
|
#2
|
Senior Member
Join Date: Oct 2005
Posts: 3,519
|
Re: GETTING DRUGS THROUGH THE BLOOD-BRAIN BARRIER 2 treat brain mets, tumors w aid of
Fascinating. Please hurry!
__________________
Brenda
NOV 2012 - 9 yr anniversary
JULY 2012 - 7 yr anniversary stage IV (of 50...)
Nov'03~ dX stage 2B
Dec'03~ Rt side mastectomy, Her2+, ER/PR+, 10 nodes out, one node positive
Jan'04~ Taxotere/Adria/Cytoxan x 6, NED, no Rads, Tamox. 1 year, Arimadex 3 mo., NED 14 mo.
Sept'05~ micro mets lungs/chest nodes/underarm node, Switched to Aromasin, T/C/H x 7, NED 6 months - Herceptin only
Aug'06~ micro mets chest nodes, & bone spot @ C3 neck, Added Taxol to Herceptin
Feb'07~ Genetic testing, BRCA 1&2 neg
Apr'07~ MRI - two 9mm brain mets & 5 punctates, new left chest met, & small increase of bone spot C3 neck, Stopped Aromasin
May'07~ Started Tykerb/Xeloda, no WBR for now
June'07~ MRI - stable brain mets, no new mets, 9mm spots less enhanced, CA15.3 down 45.5 to 9.3 in 10 wks, Ty/Xel working magic!
Aug'07~ MRI - brain mets shrunk half, NO NEW BRAIN METS!!, TMs stable @ 9.2
Oct'07~ PET/CT & MRI show NED
Apr'08~ scans still show NED in the head, small bone spot on right iliac crest (rear pelvic bone)
Sept'08~ MRI shows activity in brain mets, completed 5 fractions/5 consecutive days of IMRT to zap the pesky buggers
Oct'08~ dropped Xeloda, switched to tri-weekly Herceptin in combo with Tykerb, extend to tri-monthly Zometa infusion
Dec'08~ Brain MRI- 4 spots reduced to punctate size, large spot shrunk by 3mm, CT of torso clear/pelvis spot stable
June'09~ new 3-4mm left cerrebellar spot zapped with IMRT targeted rads
Sept'09~ new 6mm & 1 cm spots in pituitary/optic chiasm area. Rx= 25 days of 3D conformal fractionated targeted IMRT to the tumors.
Oct'09~ 25 days of low dose 3D conformal fractionated targeted IMRT to the bone mets spot on rt. iliac crest that have been watching for 2 years. Added daily Aromasin back into treatment regimen.
Apr'10~ Brain MRI clear! But, see new small spot on adrenal gland. Change from Aromasin back to Tamoxifen.
June'10~ Tumor markers (CA15.3) dropped from 37 to 23 after one month on Tamoxifen. Continue to monitor adrenal gland spot. Remain on Tykerb/Herceptin/Tamoxifen.
Nov'10~ Radiate positive mediastinal node that was pressing on recurrent laryngeal nerve, causing paralyzed larynx and a funny voice.
Jan'11~ MRI shows possible activity or perhaps just scar tissue/necrotic increase on 3 previously treated brain spots and a pituitary spot. 5 days of IMRT on 4 spots.
Feb'11~ Enrolled in T-DM1 EAP in Denver, first treatment March 25, 2011.
Mar'11~ Finally started T-DM1 EAP in Denver at Rocky Mountain Cancer Center/Rose on Mar. 25... hallelujah.
"I would rather be anecdotally alive than statistically dead."
|
|
|
Posting Rules
|
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts
HTML code is Off
|
|
|
All times are GMT -7. The time now is 02:57 AM.
|