[MOL] Info-metast. liver cancer/Sheila/Isotopes, Cell-Directed Radiation [01881] Medicine On Line


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[MOL] Info-metast. liver cancer/Sheila/Isotopes, Cell-Directed Radiation Therapy



Shiela:  Hope this helps you and am very glad to hear that your brother
is doing so well.  Thanks for the update on him.  Your friend, Lillian




Cell-Directed Radiation Therapy 



Cell-Directed Radiation Therapy provides an opportunity to deliver more
specific
radiation to tumor cells while sparing normal tissue. This new discovery
uses
millions of cancer seeking antibodies to guide radiation to the cancer.
Powerful
radioactive isotope "backpacks" are attached to the antibodies. As the
cancer
hunting antibodies flow though the blood stream, the backpacks ride
along. The
antibodies target cell surface binding sites specific to the cancer
cells. When the
antibodies bump against a cancer cell, they use arm like features to
grab hold.
Radiation from these bound radioisotopes then destroys the cancer cells
that make
up the malignant tumor. Clinical tests have been successful in treating
certain
cancers in humans. Based on successful tests in animals, studies are in
progress to
test efficacy in treating a wide number of different cancers found in
humans. In
some instances, health insurers have already recognized the
effectiveness of
Cell-Directed Radiation therapy by including it in their coverage. Food
and Drug
Administration (FDA) approval of selected approaches is expected within
five
years.

                            Research Status 



Most of the research to date using Cell-Directed Radiation Therapy has
been
focused on leukemia and lymphoma. Recently, research has expanded to
include
three of the major cancer types: lung, colon, and breast. Current
methods have
used beta emitters. Successes in treating cancer with Cell-Directed
Radiation
Therapy have been achieved at Fred Hutchinson Cancer Research Center
(FHCRC) using the beta particle emitting isotope I-131. Since I-131 is
also a strong
emitter of gamma radiation, patients must be isolated and shielded, and
health care
providers must exercise extensive radiation protection procedures.
Recently, the
isotopes Re-188 and Y-90 have been identified as two of the most
promising beta
emitting isotopes of choice. The University of California at Irvine is
planning human
trials using Re-188 in the treatment of breast and ovarian cancer.
Clinical testing
using Y-90 on human patients is being rapidly expanded at several major
medical
facilities. Trials in humans have been encouraging in the treatment of
leukemia and
lymphoma. Recently completed Phase I/II studies at Stanford University
using
Y-90 labeled antibodies in patients with recurrent B-cell lymphoma
resulted in good
localization of the monoclonal antibodies in known sites of the disease.
Among 18
patients, 72 percent had partial or complete responses, including one
complete
response of a 26 month duration. The largest single trial has been
conducted at the
M.D. Anderson Cancer Center in Houston, Texas, where more than 100
patients
with Hodgkins lymphoma have been successfully treated with antibodies
labeled
with Y-90 produced at Hanford. More than 80% of the Hodgkins lymphoma
patients, all of whom had previously failed to respond to conventional
radiotherapy
and chemotherapy, showed a positive response.

Results of animal trials have also shown remarkable success in the
treatment of
lung, colon, and breast cancer. Human clinical trials, such as those
being conducted
at Virginia Mason Medical Center, are expected to show cell-directed
radiation
therapy to be effective in treating these and other cancers. Much of the
Re-188 and
Y-90 testing is being funded by the National Institutes of Health (NIH).

Although most development and testing to date has focused on beta
emitting
isotopes, alpha emitting isotopes are expected to be more effective
under certain
circumstances. The alpha emitting isotopes have the potential to be more
locally
focused to individual cancer cells, while having less impact upon
surrounding
healthy body tissue. The alpha emitters of interest decay into charged
particles with
total energies that are five to ten times greater than those associated
with beta
emitters. Consequently, the alpha emitters are expected to be
significantly more
efficient in killing cancer cells while permitting lower doses. The
alpha emitters
should be more applicable to sensitive tissue areas that could be
damaged by the
more penetrating beta particles. Potential early applications for the
alpha emitting
isotopes include acute leukemia, prostate cancer, and breast cancer. The
higher
cancer killing potential with a smaller killing radius should make the
alpha emitters
more effective substitutes for some of the applications currently
envisioned for the
beta emitters. In some instances, some types of cancer may be most
effectively
treated by using both alpha and beta emitting Cell-Directed Radiation
therapies
during the course of treatment. 

The NIH is actively studying the treatment of cancer using the alpha
emitting
isotope of Bismuth 213 (Bi-213). The chemistry for attaching bismuth to
cancer
cell seeking antibodies was developed for treatments using certain beta
emitting
isotopes of bismuth. The first alpha emitter human trial is underway at
Sloan
Kettering in New York and the isotope being used is Bi-213. The trial is
supported
by NIH and DOE and Hanford is processing the Bi-213. DOE's Pacific
Northwest
National Laboratory (PNNL) has initiated a program to investigate the
chemistry
(both separations and chelating) issues needed to support the delivery
of the alpha
emitting isotope Radium 223 (Ra-223) for Cell-Directed Radiation
therapy. It is
evident that Ra-223 as proposed by PNNL can be produced at significantly
lower
cost than Bi-213. However, the required chemistry to attach Ra-223 to
the targeting
antibody is yet to be determined. This is being worked on at University
of Idaho
and PNNL. The earliest that Ra-223 could be in trials is late 1997. The
Fast Flux
Test Facility (FFTF) at Hanford produced Ra-223's parent isotope,
Actimium 227,
prior to the facility's shut down in 1992. 

The Bi-213 research is important in that it will give an earlyindication
of the
efficiency of alpha emitters. If the chemistry for Ra-223 does not work
out, Bi-213
is expected to become the alpha emitter of choice.

The exploration and application of Cell-directed Radiation Therapy to
the treatment
ofother diseases such as AIDS is just beginning.



hi all, my brother,nsclc is doing pretty well. will go see him in a
couple
weeks.
But now a good friend has suspected(just did biopsy which didn't get
enough
tissue to tell) mets. to the liver (she got clean bill of health a year
ago
following surg. removal of pancr. islet cell neuro. endroc. cancer at
Sloan
Kettering.
Local oncologist mentioned a M.D from Univ. of New Mexico using some
sort of
new treatment (if it does turn out to be cancer) involving isotopes she
thinks.
I told her I would check with you all.   She is due for her 1 yr. check
up at
Sloan in a couple of weeks and I'm sure will find out more too.
thanks, sheila s.
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