Head-to-Head Comparison of 68Ga-FAPI-04 and 68Ga-DOTA-TATE PET/CT in Recurrent Medullary Thyroid Cancer
Emine Göknur IşıkDuygu Has ŞimşekNurdan GülŞükrü Mehmet ErtürkFikret BüyükkayaÖzlem Soyluk SelçukbiricikYalın İşcanZeynep Gözde ÖzkanYasemin ŞanlıAyşe MudunSerkan Kuyumcu
0
Citation
37
Reference
10
Related Paper
Abstract:
We aimed to compare the diagnostic performance of 68Ga-FAPI-04 (FAPI) in comparison to 68Ga-DOTATATE (SSTR) PET/CT for patients presenting with recurrent medullary thyroid carcinoma (MTC). Sixteen MTC patients with elevated calcitonin levels (>150 pg/mL) underwent FAPI and SSTR PET/CT. Two nuclear medicine physicians evaluated all images, categorizing lesions into locoregional metastases, mediastinal lymph nodes (LNs), liver, and bone metastases. SUVmax and tumor-to-background ratio were recorded. PET modalities were compared using the McNemar test. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FAPI and SSTR PET were calculated. The cohort comprised 16 patients (50% female; mean age 50 ± 17 years). Median calcitonin and CEA levels were 6234 pg/mL and 17.3 ng/mL, respectively. In patient-based analysis, SSTR exhibited higher diagnostic sensitivity compared with FAPI (88% vs 81%), resulting a statistically significant difference (P = 0.004). Mean SUVmax and tumor-to-background ratio values were 10.3 and 5.35 for FAPI, and 9.7 and 11.9 for SSTR PET, respectively. In lesion-based analyses, FAPI demonstrated higher accuracy than SSTR for cervical LNs (91.9% vs 50%), mediastinal LNs (94.9% vs 54.4%), and liver metastases (57.4% vs 7.3%), respectively. Notably, 31% of patients (n = 5) with FAP-expressing liver lesions showed no uptake on SSTR imaging. MRI confirmed liver metastases in 3 of these patients; however, 2 FAP-expressing lesions were confirmed as hemangiomas. False-positive findings of DOTA primarily included reactive LNs and bone hemangiomas. FAPI PET presents promising outcomes in detecting metastases in recurrent MTC patients. Although its diagnostic performance matches SSTR on a per-patient basis, FAPI PET exhibits superior sensitivity and accuracy in lesion-based analyses, notably for liver and bone metastases.Keywords:
DOTA
Medullary Thyroid Cancer
PET-CT
Several exploratory studies have demonstrated the feasibility of cholecystokinin-2 receptor (CCK2R) targeting in patients with medullary thyroid carcinoma (MTC) and other neuroendocrine tumors (NETs). We report the results of a prospective phase I/IIA pilot study (clinicaltrials.gov NCT06155994) conducted at our center with the 68Ga-labeled peptide analog DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1-Nal-Phe-NH2 (68Ga-DOTA-MGS5). Methods: Six patients with advanced MTC and 6 patients with gastroenteropancreatic and bronchopulmonary NETs confirmed by previous PET/CT imaging with other PET tracers received a single dose of 180 MBq of 68Ga-DOTA-MGS5. The first 6 patients enrolled in the study were included in the dosimetry evaluation, and safety was assessed in all 12 patients. PET/CT imaging was performed at different time points after injection to perform dosimetric calculations and to determine the optimal imaging time window. In addition, blood and urine samples were collected for pharmacokinetic assessments. Results: The administration of 68Ga-DOTA-MGS5 was well tolerated, with minor adverse drug reactions occurring only in 3 patients. 68Ga-DOTA-MGS5 was cleared rapidly from the blood, with less than 21% of the injected activity present in blood 215 ± 10 min after injection. Tracer elimination occurred mainly through the kidneys, with a cumulative urinary excretion greater than 40% 3 h after injection. A high percentage of intact radiopeptide was confirmed in plasma. The highest absorbed dose was found for the urinary bladder wall, the stomach wall, and the kidneys, with an effective dose of 0.023 ± 0.007 mSv/MBq. The time points of 1 and 2 h after injection proved to be optimal for PET/CT imaging. In the 6 patients included in the dosimetry evaluation, local metastasis was confirmed in 2 patients with advanced MTC, whereas only 1 of 4 patients with gastroenteropancreatic NETs was positive in 68Ga-DOTA-MGS5 PET/CT. Conclusion: Besides confirming the safety of administration, within the phase I part of the prospective clinical trial, an acceptable effective whole-body dose, an overall favorable biodistribution, and the feasibility of cholecystokinin-2 receptor imaging could be shown for 68Ga-DOTA-MGS5.
DOTA
Biodistribution
Medullary Thyroid Cancer
Cite
Citations (0)
Sorafenib and lenvatinib can be effective for advanced differentiated thyroid cancer, and vandetanib and cabozantinib can be effective options for advanced medullary thyroid cancer. When first-line tyrosine kinase inhibitors fail for patients, evidence supports salvage therapy for differentiated thyroid cancer but is less compelling for medullary thyroid cancer.
Lenvatinib
Cabozantinib
Vandetanib
Medullary Thyroid Cancer
Salvage therapy
Cite
Citations (0)
Medullary Thyroid Cancer
Cite
Citations (3)
Medullary Thyroid Cancer
Cite
Citations (1)
Protein kinase inhibitors (PKIs) have emerged as highly promising therapies in progressive metastatic radioiodine-refractory differentiated thyroid cancer and in medullary thyroid cancer; two were recently approved in the USA for use in medullary thyroid cancer (vandetanib, cabozantinib), and another for use in progressive metastatic radioiodine-refractory differentiated thyroid cancer (sorafenib). Although more than 90% of thyroid cancer patients fare well in response to conventional treatment, PKI therapy has the potential to provide benefit. Nonetheless, PKIs produce numerous side effects, may worsen quality of life, may hasten mortality (by 1–2%), require discerning clinical acumen, are not yet proven to improve thyroid cancer survival and are very costly. This raises questions about who should prescribe PKIs, and about whether their use in thyroid cancer is truly beneficent and ethically justified. Restraint should be exercised in their use in thyroid cancer, with potential risks and benefits carefully weighed and solutions devised to help ameliorate many of the problems associated with their use.
Vandetanib
Cabozantinib
Medullary Thyroid Cancer
Cite
Citations (8)
Medullary Thyroid Cancer
Cite
Citations (0)
We report an unusual family which suggests that susceptibility to medullary and non-medullary thyroid cancer (MTC, NMTC) may be related. The index case, a woman aged 59, presented with a 3 cm nodule in the right lobe of her thyroid gland. Thyroid function tests were within normal limits. The patient’s past medical history was unremarkable. Furthermore, she was normotensive and had no clinical features suggestive of Cowden’s disease. Ultrasound examination showed the thyroid lesion was solid and a biopsy was diagnostic of a diagnosis of MTC. The patient underwent a right lobectomy of the thyroid gland with complete excision of isthmus, histology confirming the biopsy diagnosis. Her sons, aged 39 and 35 years, underwent screening for C-cell hyperplasia. Both had repeated exaggerated response to pentagastrin stimulation displaying more than 20-fold increases in circulating calcitonin. In addition each had normal thyroid function, and was normotensive with normal 24 h urinary catecholamine levels. There was no history of radiation exposure in either the mother or her two sons. Using venous blood as a source of DNA the index case was screened for a germline mutation in RET. This analysis showed that the index case possessed the V804L mutation within exon 14 that has been implicated as a cause of MEN-2A, MEN-2B and FMTC
Medullary Thyroid Cancer
Cite
Citations (0)
Medullary Thyroid Cancer
Medullary carcinoma
Cite
Citations (0)
Medullary thyroid cancer (MTC) is a rare disease.
Medullary Thyroid Cancer
Cite
Citations (2)
The treatment of thyroid cancer is evolving. The molecular mechanisms of carcinogenesis for many thyroid cancers have been investigated, and have yielded targets for potential therapies. These targets include VEGFR in the treatment of all thyroid cancers, BRAF in the treatment of papillary thyroid cancer, and RET in the treatment of medullary thyroid cancer (MTC). Many promising drugs that target one or more of these proteins are currently being evaluated, including sorafenib and sunitinib, both of which are still under development for the treatment of thyroid cancer but which have been approved for use in other malignancies. In addition, compounds such as vandetanib (AstraZeneca plc) and XL-184 (Bristol-Myers Squibb Co/Exelixis Inc) have demonstrated activity in early-phase clinical trials of MTC and are being tested further in randomized trials.
Vandetanib
Medullary Thyroid Cancer
Investigational Drugs
Follicular thyroid cancer
Targeted Therapy
Cite
Citations (6)