Novel use of ¹⁷⁷Lu-DOTA-RGD₂ in treatment of ⁶⁸Ga-DOTA-RGD₂-avid lesions in papillary thyroid cancer with TENIS

Excerpt

Thyroglobulin elevation with negative ¹³¹I scintigraphy (TENIS) in patients with differentiated thyroid carcinoma (DTC) poses a unique management challenge to the physician due to limited treatment modalities. Treatment with chemo-radiation, redifferentiation therapy, tyrosine kinase inhibitors and peptide receptor radionuclide therapy (PRRT) using somatostatin analogues have shown very insignificant clinical benefits with high incidence of adverse effects [1]. Arginylglycylaspartic acid (RGD) tripeptide sequence, having very high specificity towards α_vβ₃ integrin, is over-expressed on the tumor vasculature, including DTC and can be used as a theranostic agent [2‐4]. We present a 54-year-old woman with papillary carcinoma thyroid who developed TENIS syndrome after receiving 500 GBq of ¹³¹I in cumulative doses. She experienced significant adverse effects with no clinical improvement on sorafenib therapy for 1 year and presented with severe pain and a palpable hard mass in the pre-sternal region. ⁶⁸Ga-DOTA-RGD₂ PET/CT was performed to evaluate disease extent and for pre-therapy assessment. The maximum intensity projection (MIP) image (a) and transaxial fused PET/CT images showed increased tracer uptake in the thyroid remnant [maximum standardized uptake value (SUVmax) = 4.7] with cervical lymph nodes (b), mediastinal lymph node (c; SUVmax = 8.4), lytic skeletal lesions with soft tissue component in the sternum (c; SUVmax = 7.8) and left iliac bone (d; SUVmax = 8.4) and multiple lung nodules (e). The patient received 5.5 GBq of ¹⁷⁷Lu-DOTA-RGD₂ with post-therapy whole-body images in anterior (f) and posterior (g) views revealing the overall distribution of ¹⁷⁷Lu-DOTA-RGD₂ and transaxial fused SPECT/CT images (h–k) showing tracer uptake at sites corresponding to ⁶⁸Ga-DOTA-RGD₂ -avid lesions. The patient was followed up at 4 months post-therapy, with significant pain relief and reduced pre-sternal swelling suggesting clinical benefit. Post-therapy follow-up ⁶⁸Ga-DOTA-RGD₂ PET/CT MIP image (l) and transaxial fused PET/CT images showed tracer uptake in the thyroid remnant (SUVmax = 3.0 vs. 4.7) with cervical lymph nodes (m), mediastinal lymph node (n; SUVmax = 7.7 vs. 8.4), lytic skeletal lesions with significant reduction in soft tissue component in the sternum (n; SUVmax = 6.6 vs. 7.8) and left iliac bone (o; SUVmax 8.1 vs. 8.4) and multiple lung nodules (p), suggesting response to therapy. To the best of our knowledge, this is the first reported theranostics using ⁶⁸Ga-DOTA-RGD₂ and ¹⁷⁷Lu-DOTA-RGD₂ and can be a stepping stone for future studies.

…