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Background: The main objective is to discuss why treatment of non-prostate cancers with [177Lu]Lu-PSMA-radioligand achieved only low tumor dose in most published cases, despite high uptake on PSMA PET. We use a patient with renal cell carcinoma as an illustrative example. Furthermore, we discuss how the problem with early washout and low tumor dose might be overcome by using a radionuclide with shorter half-life, matching the target binding residence time. Case presentation: [68Ga]Ga-PSMA-11 PET/CT of a 56-year old man with metastatic renal cell carcinoma showed high lesion uptake. One dose of 6.9 GBq [177Lu]Lu-PSMA-I&T was administrated. Post-therapy dosimetry was performed with SPECT/CT and whole-body planar imaging after 5, 24 and 48 h. Doses to target lesions were only 0.2–0.5 Gy. No treatment effect was achieved. Conclusion: Rapid tumor washout of [177Lu]Lu-PSMA-I&T and low tumor dose despite high uptake of [68Ga]Ga-PSMA-11 are most likely caused by localization of PSMA-receptors on neovasculature rather than on the tumor cells, and unlike in prostate cancer cells, the PSMA-RL / PSMA-receptor complex is not internalized. To overcome the problem with early washout, the use of a radionuclide with shorter half-life matching the target binding residence time will be needed. [ABSTRACT FROM AUTHOR]

Objective: Redifferentiation therapy (RDT) can restore radioactive iodine (RAI) uptake in differentiated thyroid cancer (DTC) cells to enable salvage 131I therapy for previously RAI refractory (RAIR) disease. This study evaluated the clinical outcomes of patients who underwent RDT and identified clinicopathologic characteristics predictive of RAI restoration following RDT. Methods: This is a retrospective case series of 33 patients with response evaluation criteria in solid tumors (RECIST)-progressive metastatic RAIR-DTC who underwent RDT between 2017 and 2022 at the Mayo Clinic (Rochester, MN). All patients underwent genomic profiling and received MEK, RET or ALK inhibitors alone, or combination BRAF-MEK inhibitors for 4 weeks. At week 3, those with increased RAI avidity in metastatic foci received high-dose 131I therapy. Baseline and clinicopathologic outcomes were comprehensively reviewed. Results: Of the 33 patients, 57.6% had restored RAI uptake following RDT (Redifferentiated subgroup). 42.1% (8/19) with papillary thyroid cancers (PTC), 100% (4/4) with invasive encapsulated follicular variant PTCs (IEFV-PTCs), and 100% (7/7) with follicular thyroid cancers (FTC) redifferentiated. All (11/11) RAS mutant tumors redifferentiated compared with 38.9% (7/18) with BRAF mutant disease (6 PTC and 1 IEFV-PTC). 76.5% (13/17) of redifferentiated and 66.7% (8/12) of non-redifferentiated patients achieved a best overall RECIST response of stable disease (SD) or non-complete response/non-progressive disease. Both subgroups had a median 12% tumor shrinkage at 3 weeks on drug(s) alone. The redifferentiated subgroup, following high-dose 131I therapy, achieved an additional median 20% tumor reduction at 6 months after RDT. There were no statistically significant differences between both groups in progression free survival (PFS), time to initiation of systemic therapy, and time to any additional therapy. Of the entire cohort, 6.1% (2/33) experienced histologic transformation to anaplastic thyroid cancer, 15.1% (5/33) died, and all had redifferentiated following RDT and received 131I therapy. Conclusion: RDT has the potential to restore RAI avidity and induce RECIST responses following 131I therapy in select patients with RAIR-DTC, particularly those with RAS-driven "follicular" phenotypes. In patients with PTC, none of the evaluated clinical outcomes differed statistically between the redifferentiated and non-redifferentiated subgroups. Further studies are needed to better characterize the long-term survival and/or safety outcomes of high-dose RAI following RDT, particularly whether it could be associated with histologic anaplastic transformation. [ABSTRACT FROM AUTHOR]

B Dear Editor: b To our knowledge, all studies on radioiodine redifferentiation after pretreatment with mitogen-activated protein kinase (MAPK) inhibition so far have reported on only one treatment.[1] Although one case report indicates that repeat redifferentiation may be possible, the effects of the redifferentiation could not be assessed because of the simultaneous and continued long treatment with redifferentiation agents.[2] In this letter, we report on a patient with SP 131 sp I refractory (RAIR) BRAF SP V600E sp mutated progressive metastatic papillary thyroid cancer (PTC) successfully redifferentiated twice 14 months apart with the BRAF inhibitor dabrafenib, each followed by SP 131 sp I therapy resulting in initial clinical response. Fourteen months after the treatment, a diagnostic rhTSH-stimulated SP 123 sp I whole-body scan (WBS) and SPECT/CT did not show radioiodine uptake in the metastases (Fig. [Extracted from the article]

Background: Cytologically defined indeterminate thyroid nodules are a diagnostic challenge. Surgical lobectomy remains the gold standard for definitive diagnosis. However, 70-85% of nodules are ultimately benign. The primary objective of this study was to evaluate the negative predictive value (NPV) of F18-fluorodeoxyglucose (FDG) positron emission computed tomography (PET/CT) in excluding cancer among cytologically indeterminate thyroid nodules within the authors' institution using surgical pathology as the gold-standard reference. In addition, a systematic review was performed of published prospective studies on the NPV of PET/CT in evaluating indeterminate thyroid nodules. Methods: A retrospective review was performed of all patients aged ≥18 years seen at the Mayo Clinic between January 1, 2000, and December 31, 2014, with cytologically defined indeterminate thyroid nodules (suspicious for Hürthle cell neoplasm or follicular neoplasm; N = 858), who had a PET/CT within one year of fine-needle aspiration (n = 80) and underwent definitive diagnostic lobectomy (n = 51). Nodules were considered PET negative if they had a standardized uptake value (SUV) <5. Additionally, a systematic review was performed of published prospective studies on the NPV of PET/CT across multiple sites. Results: Fifty-one patients met the eligibility criteria. The retrospective review combined with a systematic review of eight prospective studies suggests that indeterminate nodules with a negative PET (SUV <5) have a low risk of malignancy (NPV 94%). The cancer prevalence in the institution is 14% and 27% in the combined prospective studies. Conclusions: PET/CT represents a preoperative, non-invasive tool that when combined with sonographic features can identify indeterminate nodules at low risk for malignancy. [ABSTRACT FROM AUTHOR]

Background: Graves' ophthalmopathy (GO) develops or worsens in up to one-third of patients treated with radioactive iodine (RAI) for Graves' hyperthyroidism. We sought to identify the prevalence of development or worsening of GO in patients treated with RAI for Graves' hyperthyroidism and to identify the risk factors associated with that outcome. Methods: We identified a retrospective cohort of consecutive patients treated with RAI at Mayo Clinic (Rochester, MN) between 2005 and 2006. We assessed their medical records for evidence of hypothyroidism and development or worsening of GO in the year after therapy. Hypothyroidism was defined as thyrotropin >3.0 mIU/L or free thyroxine <0.8 ng/dL. Results: We identified 291 consecutive patients who received RAI therapy during the study period, with 195 out of 291 having complete follow-up data for a one-year period. GO was present in 46 out of 195 patients (23.6%) at baseline. After RAI treatment, GO developed or worsened in 25 out of 195 patients (12.8%) and it was associated with hypothyroidism at first follow-up ( p=0.011) with an odds ratio (OR) of 3.3 [95% confidence interval (CI) 1.3-8.7]. More smokers than nonsmokers developed new or worse GO (17.7% vs. 11.8%), but that difference did not reach statistical significance ( p=0.35). Preexisting GO (24% of patients) was associated with a higher risk for negative GO outcome compared with patients who had no GO at baseline (11%; p=0.021). Both development of hypothyroidism by the first visit after RAI therapy (OR 3.6) and preexistent GO (OR 2.8) remained significant in a multivariate analysis. Development of hypothyroidism was more likely in patients with longer duration to first follow-up ( p<0.001). By 6-8 weeks after RAI treatment, the prevalence of hypothyroidism was ∼40%, while that of hyperthyroidism was only 20%. Conclusions: The presence of hypothyroidism at the first assessment of thyroid function after RAI administration is a strong predictor for adverse GO outcome. This risk is highest in patients with preexisting GO. We suggest that in order to prevent clinical hypothyroidism and the associated risk for GO, the optimal time for first measurement of fT4 is before 6 weeks after RAI therapy. [ABSTRACT FROM AUTHOR]