The Use of 124-I-PET/CT Whole Body and Lesional Dosimetry in Differentiated Thyroid Cancer

Study rationale

High risk patients with differentiated thyroid cancer (DTC) require therapy with 131 I under
thyroid stimulating hormone (TSH) stimulation. There are two methods of TSH stimulation
endogenous by thyroid hormone withdrawal (THW) leading to hypothyroidism and exogenous by
injection of human recombinant TSH (rhTSH Thyrogen). The appropriate 131-I activity utilized
for treatment is either based on empiric fixed dosage choice or individually determined
activity based on 131 I dosimetric calculations. Although dosimetry utilizing radioactive
iodine isotope 131 I enables calculation of maximum safe dose, it does not estimate the
tumoricidal activity necessary to destroy the metastatic lesions. The alternative radioactive
isotope of iodine -124 I, used for positron emission tomography (PET) imaging, might be used
for calculation not only the maximum safe131 I dose, but also to predict the absorbed dose in
the metastatic lesions.

Study objectives

The primary objective of this study is to compare the 124 I -PET/CT lesional and whole body
dosimetry in each individual patient with metastatic radioiodine (RAI)-avid thyroid cancer
under preparation with rhTSH and THW. The secondary objective is to evaluate the predicted by
PET/CT lesional uptake with the early response to therapy.

Study design

This is a phase 2 pilot prospective cohort study comparing the lesional and whole body
dosimetry within each patient undergoing exogenous (rhTSH) and endogenous (THW) TSH
stimulation and followed for 5 years.

Interventions

Each study participant will undergo rhTSH and THW-aided 124 I-PET/CT dosimetric evaluations
and will be subsequently treated with THW-aided RAI activity based on dosimetric calculations
enabling maximum safe dosage. The patients will be followed in 12+/-3 months intervals for 5
years.

Sample size and population

This pilot study will include 30 patients with high risk differentiated thyroid cancer
presenting with distant and/or loco-regional metastases.

- INCLUSION CRITERIA:

- Patients with established thyroid cancer diagnosis based on the pathology report
reviewed at the National Institutes of Health, who:

- underwent total thyroidectomy +/- neck lymph node dissection as clinically
indicated,

- are presenting with known per structural imaging (US neck, CT or MRI
neck/chest/abdomen/pelvis) persistent/recurrent disease either locally advanced
or presenting with distant metastases; or

- are presenting with suspected persistent/recurrent locoregional or distant
metastases based on the high risk features such as advanced tumor per pathology
report (tumor size >4 cm, exrathyroidal extension, higher risk pathology such as
tall cell, columnar cell, poorly differentiated variant, follicular thyroid
cancer with gross vascular invasion, positive margins after the surgery, bulky
lymphadenopathy in the central and/or lateral neck), detectable/increasing
baseline/suppressed thyroglobulin (Tg) level or detectable/increasing anti-Tg
antibody titers if anti-Tg antibodies are present.

- are either RAI-naive or requiring repeated RAI therapy for locally advanced
disease or distant metastases.

- Underwent imaging with MRI of the brain and spine with gadolinium contrast to
screen for the brain/spine metastases.

- Age greater than or equal to 18 years of age.

- 24 hour urine iodine excretion of less than or equal to 150 micro grams/24
hour.

EXCLUSION CRITERIA:

-Patients with non-RAI avid disease documented by negative post-therapy whole body scans
performed after previous RAI treatments.

- Serious underlying medical conditions that restrict diagnostic testing or therapy such
as renal failure, congestive cardiac failure or active coexisting non-thyroid
carcinoma, severe depression which might be exacerbated by thyroid hormone withdrawal.

- Patients with spinal or brain metastases as they are at risk of TSH-stimulation
induced swelling of metastatic lesions leading to potentially detrimental side
effects. These patients will be evaluated per the standard of care protocol
77-DK-0096.

- Pregnant or lactating women.

- Adults who are incapable of providing informed consent.