Pilot for high-resolution SPECT imaging of breast cancer lumpectomy specimens for 3D identification and quantification of resection margins.

A small breast tumor can be treated safely with breast-conserving surgery. This
leads to a very high chance of local control of the disease, as long as the
resection is radical microscopically and the remaining breast tissue is
adequately irradiated.

The treatment after lumpectomy is largely dependent on the evaluation of the
resection margins. If the tumor reaches into the resection margin
microscopically, a re-excision is indicated. When the tumor is too close to or
in the resection margin, this determines the location of an extra 'boost'
during radiation treatment.

Although the margins of a specimen are marked with sutures and/or ink, the
evaluation of resection margins in a lumpectomy specimen is challenging due to
distortion of the specimen. It is also impossible for the pathologist to
examine the entire specimen microscopically; only a selection of slices can be
viewed based on visual inspection of the sample. Therefore it is possible that
a close- or positive resection margin is missed in some cases, is not located
correctly, or not measured correctly. This might lead to suboptimal treatment
with surgery or radiotherapy and thereby raising the chance for a local relapse
of disease.

The radioactive tracer Technetium-99m-SestaMIBI is accumulated in breast
tumors. Single photon emission computed tomography (SPECT) for imaging of this
tracer, and sometimes in combination with CT for anatomical localization, is a
known technique for detection of breast cancer. However, due to a limited
resolution, this technique is only suitable for imaging of macroscopic tumors.

At the AVL a high-resolution SPECT/CT scanner is available. Although this is a
pre-clinical scanner, is can also be used for scanning of tissue specimens with
maximum dimensions of about 4x4x8 cm. With this equipment, molecular imaging
with high sensitivity can reach a spatial resolution of approximately 0,25 mm.
The current clinical imaging equipment does not reach these specifications.

The hypothesis is that with these high-resolution SPECT images, the pathologist
can be made aware of regions with a high risk for close or irradical resection
margins prior to histopathological examination. Also the location of a positive
resection margin can be identified more easily using the images. To determine
the value of this new methodology, the image quality and feasibility of
high-resolution SPECT/CT of lumpectomy specimens must be evaluated.

Pilot for determining the feasibility and image quality of high resolution
Tc99m-SestaMIBI imaging of lumpectomy specimens for detection, localization,
and quantification of resection margins.

Five days prior to surgery the patient scheduled for lumpectomy with proven cT1
cNx invasive ductal carcinoma (IDC) (n=3), ductal carcinoma is situ (DCIS)
(n=3) receives all patient information on paper and orally from one of the
involved researchers. The patient consents for a SestaMIBI-99m injection at the
day of surgery, preoperative imaging at the nuclear medicine department, and
the patient*s tumour specimen is scanned by high-resolution SPECT after surgery
prior to standard pathological evaluation.

During surgery 500MBq Technetium-99m (Tc-99m) SestaMIBI is intravenously
administered in the contralateral arm by a nuclear physician or one of the
researchers with a radiation expertise level III certificate.

For the surgeon and patient the whole surgical procedure is according to
standard clinical protocol, however the time between injection and excision
should be minimally 10 minutes. Straight after the excision of the specimen,
the specimen is placed in a Perspex container and transported in an iced box to
the U-SPECT+/CT. The anatomical orientation is marked at the specimen for
correlation of the images.
A 3D SPECT-scan is made of the specimen in the container with a scanning time
of approximately 30 minutes. This is followed by a high resolution CT-scan for
anatomical correlation and verification of the I125-seed. If possible, a
MRI-scan is acquired at the preclinical scanner for further detailed images of
the lesion. Within 1 hour the specimen is delivered at the pathology department
for standard histopathological examination.

Participation is not associated with significant risks for patients or
personnel.

During a normal lumpectomy procedure, patients can receive a low dose of
radiation from a ROLL procedure (1mSv), SN procedure (2 mSv), and/or
localization with iodine seeds (1 mSv). For this study an extra intravenous
injection with 500 MBq Tc99m-SestaMIBI is given, with an additional radiation
dose of 4.5 mSv. This is within normal limits for diagnostic procedures and no
risks or side-effects are expected. However, women younger than 58 years old
are excluded from this study due to the radiation.