Ravinder K. Grewal

For liver-directed parenteral therapies in cholangiocarcinoma and colorectal liver metastases, the hepatic arterial infusion pumps (HAIPs) are used to maximize the drug concentrations within the malignant tumors. The patency and normal functioning of the HAIP system is assessed by radionuclide imaging with ^99mTc-MAA. We bring forth a relatively rare instance where the rate of infusion of the radiopharmaceutical determines the appearance of the hepatogram in the scan. Article published online: 05 July 2025 © 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

Background: Fluorine 18-labelled tetrafluoroborate ([¹⁸F]TFB) is a substrate for the sodium/iodide symporter. In thyroid cancer, [¹⁸F]TFB-PET/CT may be an alternative to iodine imaging to evaluate the extent of disease, eligibility for radioiodine treatment, and success of redifferentiation therapies. We report the results of a pilot study to determine tumor uptake of [¹⁸F]TFB and compare its properties to [¹²⁴I]IodinePET/CT in patients with metastatic thyroid cancer. Methods: Five patients were included in a prospective study. All patients received PET/CT 1 h after injection of 356 ± 12 MBq [¹⁸F]TFB and were given 230 ± 9 MBq [¹²⁴I]Iodine orally on the same day, followed by PET/CT after 48 h. Before redifferentiation therapy, patients underwent an additional baseline [¹²⁴I]Iodine PET/CT. Cases were analyzed by two board-certified specialists. Detection rates and Spearman correlation for [¹⁸F]TFB and [¹²⁴I]Iodine were calculated. Results: Three patients had poorly differentiated thyroid cancer and received trametinib in a redifferentiation trial. Two patients had papillary thyroid cancer and did not receive redifferentiation therapy. Of the 33 lesions seen before/without redifferentiation therapy, 19 (58%) were visible on [¹⁸F]TFB and 30 (91%) on [¹²⁴I]Iodine imaging. In the patients who underwent redifferentiation therapy, 48 lesions were newly seen on [¹²⁴I]Iodine PET/CT with a median SUV_max of 3.3 (range, 0.4–285.0). All of these lesions were [¹⁸F]TFB-negative. Conclusion: [¹⁸F]TFB failed to predict radioactive iodine uptake in patients with poorly differentiated thyroid cancer who underwent redifferentiation therapy with trametinib. It is unclear whether such discrepancies may also occur in other redifferentiation therapies or may even be encountered in redifferentiation-naïve thyroid cancer. Trial registration number: NCT03196518, registered on June 22, 2017.

6099 Background: For patients with radioactive iodine (RAI)-refractory, recurrent/metastatic thyroid cancer, treatment entails indefinite exposure to tyrosine kinase inhibitors and their associated toxicities. The mitogen activated protein kinase (MAPK) signaling pathway is commonly activated in thyroid cancer and suppresses genes required for iodine uptake and retention, leading to RAI refractoriness. In a previous pilot study, the MEK inhibitor selumetinib restored RAI uptake; however, the response was attenuated in patients with BRAF-mutant tumors. Methods: We are conducting a study to determine whether direct targeting of BRAF activity with vemurafenib in patients with BRAF-mutant thyroid cancer reverses RAI-refractoriness. The primary objective is to determine the proportion of patients with restoration of RAI uptake sufficient to enable therapeutic RAI. Patients were stimulated with thyrotropin alfa and underwent 124I PET scans prior to and 4 weeks after treatment with vemurafenib (960mg oral twice daily). Patients whose second 124I PET scan demonstrated that > 2000 cGy could be delivered to a lesion using < 300 mCi of 131I, received therapeutic 131I while continuing vemurafenib. Results: 12 patients with BRAF-mutant thyroid cancer were enrolled; 2 were removed from study prior to the second 124I PET scan and were replaced. The median age was 68 (range 43-72) with 7 (58%) men. Vemurafenib increased 124I PET lesional dosimetry sufficient to warrant therapeutic 131I in 4 of 9 evaluable patients. Of these, 3 exhibited tumor regression (1 PR, 2 SD) at 6 months following RAI and 1 has yet to undergo follow-up imaging. Decrease in thyroglobulin levels and tumor regressions on vemurafenib prior to RAI were observed. Analysis of transcriptional signatures to assess MAPK pathway inhibition and thyroid-specific gene expression is ongoing. Conclusions: These preliminary results suggest that vemurafenib can enhance RAI incorporation and efficacy in a subset of patients with BRAF-mutant thyroid cancer. We are currently investigating whether MAPK or thyroid-specific transcriptional output markers in tumor specimens identify patients most likely to respond. Clinical trial information: NCT02145143.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by small benign tumors of mesenchymal origin also known as phosphaturic mesenchymal tumors mixed connective tissue variant. Excellent prognosis is expected with eradication of the culprit tumor. These small tumors are notoriously difficult to localize with conventional imaging studies; this often leads to an extensive work up and prolonged morbidity. We report a patient with clinical diagnosis of TIO whose culprit tumor was localized with Ga-68 DOTATOC PET/CT and MRI. Biopsy and cryoablation were performed under Ga-68 DOTATOC PET/CT guidance. Autoradiography of the biopsy specimen was performed and showed in situ correlation between Ga-68 DOTATOC uptake and histopathology with millimeter resolution.

The objective of this study was to determine whether posttherapy ¹³¹I SPECT/CT changed the need for additional cross-sectional imaging or modified the American Thyroid Association risk of recurrence classification. We performed planar imaging and SPECT/CT in a consecutive series of patients after ¹³¹I therapy. Methods: Planar imaging and SPECT/CT were performed on 148 consecutive patients with thyroid carcinoma (125 papillary, 2 follicular, 8 Hürthle cell, and 13 poorly differentiated) approximately 5 d after the therapeutic administration of 1,739–8,066 MBq (47–218 mCi) of ¹³¹I. The indication for treatment was postsurgical ablation (n = 109) or recurrent or metastatic disease with rising thyroglobulin levels (n = 39). SPECT/CT scans were obtained for all subjects for 1 bed position (38 cm), which included the neck and upper chest. Additional SPECT/CT scans of the abdomen or pelvis were acquired if suggestive findings were noted on planar images. All patients were treated in real time, according to the standard of care in our practice. At that time, clinical decisions regarding thyroid tumor classification were made by our multidisciplinary group based on all data, including operative findings, pathology, imaging, and thyroglobulin levels. In a retrospective analysis, planar and SPECT/CT images were interpreted independently, and sites of uptake were categorized as likely benign, malignant, or equivocal. An experienced thyroid endocrinologist used a combination of surgical histopathology and scan findings to determine whether additional cross-sectional imaging was required and determined if the imaging findings changed the patient's risk category. Results: In 29 patients, 61 additional cross-sectional imaging studies were avoided using SPECT/CT, compared with medical decision making based on the planar images alone. In 7 of 109 postsurgical patients, SPECT/CT findings changed the initial American Thyroid Association risk of recurrence classification. The sensitivity of planar imaging and SPECT/CT for identification of focal ¹³¹I uptake in the thyroid bed was similar in the postsurgical and recurrence cohorts. For metastatic disease in the neck, characterization of ¹³¹I uptake by SPECT/CT in the postsurgical group was significantly better than that by planar scanning (P < 0.01). Among the 109 postsurgical patients, the characterization of iodine uptake in the lung, liver, and bone was also more accurate using SPECT/CT than planar scanning (P < 0.01). The CT portion of SPECT/CT demonstrated non–iodine-avid lesions in 32 of 148 patients. Conclusion: SPECT/CT data provided information that reduced the need for additional cross-sectional imaging in 29 patients (20%) and significantly altered the initial risk of recurrence estimates in 7 of 109 patients (6.4%), thereby altering patient management recommendations with regard to frequency and intensity of follow-up studies.

Salivary gland side effects (SSEs) can be a source of significant morbidity in thyroid cancer patients receiving radioactive iodine (RAI) for remnant ablation or therapy. However, the incidence, time course, and ultimate resolution of SSEs that develop in the first few months after a single administered activity of RAI for remnant ablation has not be adequately defined. Methods: We retrospectively reviewed the clinical records of patients after RAI remnant ablation (RRA) to determine the incidence of salivary gland–related side effects reported within the first year of RRA, the dose-response relationship between administered activity and specific SSEs, and the incidence of specific SSEs based on the method of preparation for remnant ablation (recombinant human thyroid-stimulating hormone [rhTSH] vs. traditional thyroid hormone withdrawal [THW]). Results: SSEs were reported within the first year of RAI ablation in 39% of a cohort of 262 patients (66% women, 93% papillary thyroid cancer; median dose, 5,217 MBq [141 mCi]). Persistent side effects were noted after a median of 7 y in 5% or less of the entire cohort. However, when side effects developed in patients during the first year, the incidence of persistence of the symptom at last follow-up ranged from 5% to 13%. A statistically significant dose response was seen between administered activity of RAI and development of salivary gland swelling (P = 0.001, logistic dose-response curve) but not with dry mouth (P = 0.63), altered taste (P = 0.27), or salivary gland pain (P = 0.152). SSEs developed in 14% of patients receiving administered activities of 1,110 MBq (30 mCi); administered activities of 2,775 MBq (75 mCi) or more were associated with symptoms in 40% of patients (P = 0.046). Despite receiving a statistically higher administered activity (5,661 ± 2,997 MBq [153 ± 81 mCi] for THW vs. 4,958 ± 2,294 MBq [134 ± 62 mCi] for rhTSH), THW was associated with a lower rate of salivary gland swelling than the rhTSH preparation (20% vs. 10%; P = 0.017), without differences in the development of dry mouth, altered taste, or salivary gland pain. Conclusion: Although SSEs occurred in 39% of patients after routine RRA, they were usually transient, so that the overall incidence of persistent side effects at a median follow-up of 7 y was only 5%. Even though the risk for persistent side effects is rather small, these data do emphasize the need to select patients carefully for RRA who are thought to be at moderate to high risk for recurrence and to use the minimally effective dose of RAI activity, in an attempt to maximize the potential benefit while minimizing the risk for adverse events for an individual patient.

The routine use of PET/CT fusion imaging in a large oncology practice has led to the realization that (18)F-FDG uptake into normal fat and muscle can be a common source of potentially misleading false-positive PET imaging in the neck, thorax, and abdomen. The goal of this study was to characterize this normal variant of (18)F-FDG uptake in terms of incidence and characteristic extent. All body scans done on our PET/CT scanners in July and August 2002 were retrospectively reviewed. All cases in which increased (18)F-FDG uptake in the neck was not localized to lymph nodes or other obvious anatomic sites on the CT scans were included in this study. Sites of any unexplained (18)F-FDG uptake in the rest of the body were also recorded. A total of 863 PET scans (476 males, 387 females; age, 2-88 y; mean age, 57 y) were reviewed. The following distinctive patterns of nonpathologic (18)F-FDG activity were observed: (a) neck fat, 20 patients (2.3%); (b) paravertebral uptake, 12 patients (1.4%); (c) perinephric fat, 7 patients (0.8%); (d) mediastinal fat, 8 patients (0.9%); (e) normal musculature, 12 patients (1.4%). Patients showing paravertebral uptake, perinephric fat, and mediastinal fat were all associated with the neck fat pattern, singly or in combination. On the other hand, patients showing the normal musculature pattern did not show any of the other uptake. In this analysis, the incidence of (18)F-FDG uptake in sites other than the neck is restricted to the patient population with neck fat uptake and may be an underestimation of the true incidence. Neck fat is found predominantly in females, whereas normal musculature is usually seen in males (P < 0.01, Fisher exact test). Neck fat is also seen significantly more in the pediatric population (4/26 = 15%) than in the adult population (16/837 = 1.9%) (P < 0.01, Fisher exact test). Increased (18)F-FDG uptake is sometimes seen in individual muscles and in adipose tissue in the neck and shoulder region, axillae, mediastinum, and perinephric regions. There is also associated (18)F-FDG uptake in the intercostal spaces in the paravertebral regions. (18)F-FDG uptake in neck fat is more commonly seen in female patients and the pediatric population. The pattern of uptake as well as the age and sex distribution suggest that the (18)F-FDG in fat is in the brown adipose tissue. It is important to recognize this uptake pattern to avoid false interpretation of this benign normal variant as a malignant finding on (18)F-FDG PET scans.