A proportion of differentiated thyroid carcinomas may lose the ability to uptake radioiodine and become refractory to I-131, often accompanied by increased expression of somatostatin receptors (SSTR). This creates a therapeutic opportunity for peptide receptor radionuclide therapy (PRRT) using Lutetium-177 Dotatate. Although Ga-68 DOTA-SSA PET/CT is widely used for pre-therapy evaluation, its short half-life limits its use for dosimetry. This study explores the role of Lu-177 Dotatate as both a pre-therapy imaging agent and a therapeutic option in radioiodine-refractory differentiated thyroid cancer (RrDTC).

Patients with RrDTC underwent diagnostic imaging with 5 mCi Lu-177 Dotatate. Those demonstrating significant radiotracer uptake proceeded to PRRT unless contraindicated by renal dysfunction, bone marrow compromise, or acute illness. A modified amino acid infusion was administered before and after Lu-177 Dotatate injection for both imaging and therapy procedures.

Sixteen patients (6 males, 10 females; mean age 57.6 years) underwent pre-therapy imaging. Of these, 5 patients (31.25%) showed significant uptake, 1 (6.25%) showed faint uptake, and 10 (62.5%) showed no uptake. All five patients with significant uptake received PRRT (3,700 MBq per cycle), completing 2–4 cycles. Post-therapy scans demonstrated biodistribution patterns consistent with the pre-therapy images. Among the treated patients, three achieved partial remission, one had stable disease, and one experienced disease progression. No serious adverse events were observed within two months of treatment.

A minority of RrDTC patients exhibit sufficient Lu-177 Dotatate uptake to qualify for PRRT. Pre-therapy Lu-177 Dotatate imaging permits reliable same-agent dosimetry and shows strong concordance with post-therapy distribution. PRRT may serve as an alternative or complementary therapeutic option in patients who are unsuitable for or lack access to TKI therapy, and offers particular value in settings without PET/CT availability.