Given that
proliferating hematopoietic stem cells are especially
radiosensitive, the bone
marrow is a potential
organ at risk, particularly with the use of concurrent chemotherapy
and radiotherapy. Existing data on
bone
marrow distribution have
been determined from the weight and visual appearance of the
marrow in cadavers.
18F-fluoro-l-deoxythymidine
concentrates in bone
marrow, and we used its
intensity on positron emission tomography imaging to quantify the
location of the proliferating
bone marrow.
The hematopoietic stem cells
in the bone
marrow that are
continually replacing circulating peripheral blood cells are among
the most radiosensitive cells in the body. Data exist suggesting
that radiation doses as low as 2–4 Gy delivered within 1–3 days can
cause a significant reduction in
bone
marrow cellularity and
proliferation , and doses of 30–40 Gy in conventional fractionation
can lead to complete ablation of the
bone
marrow. In
addition to the radiation dose, the volume of
bone
marrow irradiated is an
important factor. As the volume of actively proliferating
bone
marrow irradiated
increases, the total hematopoietic output decreases precipitously.
Taken to its extreme, only 4.5 Gy of total body irradiation is
estimated to be necessary to cause death in 50% of humans. Depending
on the dose delivered and volume treated, it can also take a
considerable period for the
bone marrow to
recover. In a study of Hodgkin's patients treated with total nodal
irradiation, Rubin found that
bone marrow
suppression frequently lasted for ≥1 year.
Although many larger
volume RT techniques have recently fallen out of favor (e.g., total
nodal irradiation, hemibody irradiation, whole abdominal radiation),
newer techniques such as intensity-modulated RT (IMRT) are
delivering lower radiation doses to ever-enlarging volumes of
adjacent normal tissues, including the
bone
marrow. In addition,
myelosuppressive chemotherapy is now frequently delivered
concurrently with RT, which, when given together, can place greater
stress on the bone
marrow than either
alone.
The available data
regarding the distribution of actively proliferating
bone
marrow in adults might
not be entirely accurate. Most of these data were studied >50 years
ago and were determined by weighing bones from cadavers before and
after heating and visual inspection of the color of the
marrow/ Although data
have been published using radionuclides such as
59Fe and
52Fe to estimate the erythroid component and
99mTc-labeled nanocolloids to image
the distribution of reticuloendothelial cells, most of these data
either provided no quantitative information regarding the
distribution of the bone
marrow or reflected only
a component of hematopoietic
marrow function.
To date, most positron
emission tomography (PET) in oncology has used
18F-flurodeoxyglucose (FDG), which
is taken up more readily by metabolically
active tissues,
including most malignancies. FDG probably does reflect
marrow proliferative
activity to some extent, as demonstrated by the increased uptake in
response to growth factor stimulation, including the use of
granulocyte colony-stimulating factor. However, areas known to
harbor proliferating bone
marrow generally have
relatively low FDG uptake, limiting its ability to quantify the
bone
marrow distribution.
In addition to an
increase in the range of radiotracers available for use during PET
scanning, advances have also been made in how the PET data are
collected. In particular, most current PET scans are now obtained
with computed tomography (CT) (i.e., PET/CT). This advance has
allowed, not only for better PET images as a result of improved
tissue attenuation correction, but also, and equally important, the
ability to link radiotracer uptake to specific anatomic structures,
including bone
marrow cavities.
The
18F-fluoro-l-deoxythymidine
positron emission/computed tomography scans performed at the Peter
MacCallum Cancer Centre between 2006 and 2009 on adult cancer
patients were analyzed. At a minimum, the scans included the
mid-skull through the proximal femurs. A software program developed
at our institution was used to calculate the percentage of
administered activity in 11 separately defined bony regions.
Results
The mean percentage of
proliferating bone
marrow by anatomic site
was 2.9% at the skull, 1.9% proximal humeri, 2.9% sternum,
8.8% ribs/ clavicles, 3.8% scapul, 19.9% thoracic spine, 16.6%
lumbar spine, 9.2% sacrum, 25.3% pelvis, and 4.5% proximal femurs.