Sestamibi Scans In Thyroglobulin Positive Scan Negative Differentiated Thyroid Cancer Patients

This study is being done to see if the radioisotope 99mTc sestamibi scans can locate what is
causing the elevated serum thyroglobulin in persons with differentiated thyroid cancer who
have elevated serum thyroglobulin levels and negative diagnostic imaging tests.

This is for patients with:

- Elevated suppressed or stimulated thyroglobulin level (Tg) > 10 ng/ml with or WITHOUT
thyroglobulin antibodies ,

- All NEGATIVE standard diagnostic clinical imaging studies (NSDCIS) = negative ultrasound
(US), diagnostic radioiodine scan (DRS), chest-x-ray (CXR), computer tomography with or
without contrast (CT), and 18F-Fluoro-deoxyglucose positron emission computer tomography
scan (18F-FDG PET) within the last 12 mos.

- If EDCIS (extensive diagnostic clinical imaging studies of 18F-sodium fluoride positron
emission computer tomography scan (18F NaF PET) or 99mTc methylene diphosphonate bone
scan (99mTc MDP), AND negative brain CT or magnetic resonance (MR) are performed, these
are also negative.

Voluntary patients will have sestamibi scan performed in 4 phases:

Phase 1: receive an injection into their vein of a radioisotope called 99mTc sestamibi.

Phase 2: wait for 60 to 90 minutes in a waiting room

Phase 3: imaged lying face up on an imaging table while a camera passes around you from the
top of the head to approximately the level of knees. This requires approximately 45 minutes

Phase 4: images will be reviewed by the nuclear medicine physician. This will take ~10-15
minutes. If additional images are required to clarify an image, then additional images of
that area will be performed on the same camera or an alternate camera. As earlier, the
additional images performed lying face up. These images require ~20-45 minutes. The patient
will then be released.

Interpretation of 99mTc Sestamibi Study.

A. A team of two blinded nuclear medicine physicians will interpret the 99mTc sestamibi, and
any area of radioactivity will be graded as by a standard nuclear medicine grading system:

1. Normal physiological activity

2. Probably physiological activity

3. Indeterminate activity

4. Probably metastatic disease

5. Metastatic disease

B. Criteria for "final determination" regarding whether a finding represents physiological
activity or metastatic disease:

1. For findings graded as 1 or 2, they will be defined for this study as physiological
activity.

2. For findings graded as 3, or 4, the following will be required:

i. Biopsy; however, this will only performed if clinically indicated.

1. Follow-up: It is anticipated that very few biopsies will be performed and because the
criteria for entering this study is NDCIS or NECIS, the only alternative for confirming
whether or not a foci of 99mTc sestamibi uptake on a scan is metastases will be follow up,
which will be performed on a clinical bases. However, if on follow up any of the following
occur, then the focus will be categorized as a metastases (true positive).

1. Subsequent biopsy,

2. Subsequent clinical imaging study(s) (For example, although a lytic bone lesion in the
area of interested was not present initially on the CT, a lytic lesion indicative of
metastases may subsequently develop in that area, and for this study this will be
defined as evidence of metastases of DTC (true positive).

ii. Blind I-131 treatment** with or without a prefatory scan: If a "blind" I-131
treatment" is clinically selected and the post I-131 therapy scan demonstrates uptake in
the same areas as the 99mTc sestamibi, then the finding on the 99mTc sestamibi will be
classified for this study as a metastases of DTC.

3. Grade 5 is not anticipated, because unlikely I-131, which can have patterns that are
very specific for DTC, 99mTc sestamibi patterns are not specific for DTC.

- A "blind I-131 treatment" is a potential therapeutic option, and this term means
that the treating physician or team cannot identify the source of the patient's
elevated Tg, but because of factors such as the level of elevated Tg, the rate of
rise of the Tg, and the patient's clinical situation, a therapeutic administration
of I-131 is give despite being "blind" to the source of the Tg.

Inclusion Criteria:

- > 18 years of age;

- Diagnosed with differentiated thyroid carcinoma;

- At least one prior I-131 therapy, which may be remnant ablation, adjuvant treatment,
and treatment of distant metastases,

- Elevated suppressed or stimulated thyroglobulin level (Tg) > 10 ng/ml with or WITHOUT
thyroglobulin antibodies ,

- All NEGATIVE standard diagnostic clinical imaging studies (SDCIS) = negative
ultrasound (US), diagnostic radioiodine scan (DRS), chest-x-ray (CXR), computer
tomography with or without contrast (CT), and 18F-Fluoro-deoxyglucose positron
emission computer tomography scan (18F-FDG PET) within the last 12 mos.

- If extensive diagnostic clinical imaging studies (EDCIS) of 18F-sodium fluoride
positron emission computer tomography scan (18F NaF PET) or 99mTc methylene
diphosphonate bone scan (99mTc MDP), AND brain CT or magnetic resonance (MR) are
performed, these are also negative.

Exclusion Criteria:

- < 18 years of age;

- Pregnant or breast feeding

- Any SDCIS or EDCIS that is positive and/or suggestive of recurrent and/or distant
metastases secondary to DTC. If a study is indeterminate, this will be forwarded to a
committee for review and resolution.