Post-therapeutic Scan Research Articles

Optimizing the indication of initial radioiodine oncolytic treatment for metastatic differentiated thyroid cancer by diagnostic 131I scan

As a classic theranostic radiopharmaceutical, radioiodine (131I) has been utilized in the management of differentiated thyroid cancer (DTC) for more than 8 decades, and the refinement of its clinical practice has been raised recently. This study was conducted to evaluate the efficiency of a diagnostic (Dx) 131I scan in optimizing the indication of initial radioiodine oncolytic treatment (ROT) for metastatic DTC by predicting therapeutic outcomes. A total of 100 patients (Dx positive, n=29; Dx negative, n=71) were eligible for patient-based analysis. The matching rate was 83.0% between the Dx and the post-therapeutic scans (kappa=0.648, P<0.001). The biochemical remission rate and structural shrinkage rate induced by the initial ROT in the Dx-positive group were, respectively, greater than those in the Dx-negative group (83.3% vs. 17.4%, P<0.001; 37.9% vs. 4.2%, P<0.001). Notably, the predictive values of positive Dx scans for ROT responsiveness and negative Dx scans for ROT nonresponsiveness reached up to 89.7% and 84.5%, respectively. This Dx scan approach seems viable in characterizing the 131I-avidity of metastatic DTC and plays a pivotal role in optimizing the indication of initial ROT for metastatic DTC.

Clinical Implications of Adding SPECT/CT to Radioiodine Whole-Body Scan in Patients With Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis.

This study aimed to determine the usefulness of adding SPECT/CT to radioiodine whole-body scans (WBSs) for the treatment of differentiated thyroid cancer (DTC). A systematic review and meta-analysis were performed following the PRISMA guidelines (PROSPERO registration: CRD42022341732) to compare the feasibility of conclusive readings and the frequency of changes in treatment plans in patients with DTC undergoing WBS + SPECT/CT versus WBS. MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles concerning thyroid cancer, radioactive iodine, and SPECT/CT or SPECT, published before August 16, 2023. Studies not comparing WBS + SPECT/CT with WBS, those lacking target outcomes, and those not involving human subjects were excluded. The risk of bias was assessed using the RoBANS 2.0 (Risk of Bias Assessment Tool for Nonrandomized Studies) tool. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system was used to evaluate the quality of evidence and strength of recommendations. A total of 30 studies (prospective n = 9, retrospective n = 21) were included in the meta-analyses. Adding SPECT/CT to WBS was shown to increase conclusive readings for cervical lesions, extracervical lesions, and all regions. Lesion-based analyses showed improvements of 14%, 20%, and 18%, respectively, whereas scan-based analyses showed improvements of 27%, 9%, and 34%. The addition of SPECT/CT to WBS led to changes in 30% of treatment plans after diagnostic scans and 9% of treatment plans after posttherapeutic scans. The quality of evidence and strength of recommendations were low. Compelling evidence demonstrates that the addition of SPECT/CT to WBS improves lesion localization, diagnostic performance, and therapy plan for patients with DTC.

Therapeutic Outcomes of 177Lu-PSMA Targeted Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: A Single-Center Study.

This study aimed to evaluate the therapeutic outcomes of 177Lutetium (177Lu)-PSMA-617 in metastatic castrate-resistant prostate cancer (mCRPC) patients, based on post-treatment imaging findings. All post-therapeutic scans were collected retrospectively from patients treated with 100-200 mCi 177Lu-PSMA-617 from March 2018 to December 2020 for mCRPC. Two independent readers interpreted the scans and visually categorized them into three strata: responsive, stable, and progressive. The responses were defined based on changes in the number of detected lesions, as well as the intensity of the hottest lesion. Data were registered, and the trend of changes was descriptively discussed. Out of 36 patients (aged 67±8.8 years), 23 underwent at least two treatment cycles. Nineteen patients (82.6%) had bone metastases, 12 (52.2%) had nodal metastases, 5 (21.7%) had liver metastases, and 3 (13.0%) had lung metastases. Eleven patients (47.8%) were considered responsive in the post-therapeutic scans, two of which experienced complete eradication of the metastatic sites. Three patients (13%) were categorized as progressive, and 9 (39.1%) patients remained stable. Regarding mortality, nine patients died during the late follow-up (median of 24 months). In the surviving population, 65% reported no or mild pain in the final follow-up, based on a 5-point scale pain assessment. The treatment of mCRPC patients with 177Lu-PSMA-617 may limit their disease progression and preserve their physical performance, which are important factors in their survival and quality of life.

Rare sites of metastases in patients with differentiated thyroid carcinoma and added value of SPECT/CT over planar whole body radioactive iodine scan

BackgroundBeing aware of the unusual or rare location of thyroid metastases helps in early diagnosis and proper patient management. Rare metastases (RM) can be missed resulting in diagnostic pitfalls and delayed treatment. The use of single-photon emission computed tomography/computed tomography (SPECT/CT) imaging in the follow-up of differentiated thyroid cancer (DTC) patients provides precise anatomical localization and characterization of RM that may be missed or misinterpreted in planar whole body iodine-131 (WBI) scan. There is a lack of knowledge about dealing with such patients, the treatment they should receive, and therapy response due to the rarity of such cases. In this work, we reported these rare cases increasing awareness about them and their methods of treatment with response to therapy and evaluated the added value of SPECT/CT imaging in changing patients’ management.Materials and methodsIn this study we reviewed all patients with DTC referred to our unit either for initial radioactive iodine-131 therapy (RAIT) or under follow-up from January 2019 to January 2022. When a suspected lesion was detected in a conventional planar WBI scan whether follow-up scan or post-therapeutic scan, SPECT/CT was acquired immediately in the same session for that region. Additional imaging modalities were performed for confirmation. Response to the given treatment either disease progression (DP) or favorable response which include complete response (CR), partial regression (PR) and stable disease (SD) recorded for each patient.ResultsTwo hundred and forty patients with DTC referred to our unit over a three-year period (from January 2019 to January 2022) were reviewed. Forty patients developed lung and bone distant metastases. Twenty-one patients were thought to have metastases at unusual sites. Due to incomplete data (no SPECT/CT pictures or confirmatory imaging), 6/21 patients were eliminated. We studied 15 patients with RM (9 females, 6 males) with a median age of 52 years (range 27–79). All patients received the initial RAIT after thyroidectomy in addition to other therapeutic modalities, e.g., radiotherapy (RTH), chemotherapy (CTH) or surgical tumor excision after detection of RM. Ten out of 15 patients (66.67%) showed favorable response to therapy (2 patients had CR, 6 patients had PR and 2 patients had SD), whereas only 5 patients had DP. Additional SPECT/CT changed management in 10/15 patients (66, 67%) of patients.ConclusionRM identification is mandatory to avoid misdiagnosis and delayed therapy. Increasing the awareness about such rare cases allows for better management. SPECT/CT could significantly impact patients' management through its precise anatomic localization and lesion characterization.

Lodine-131 uptake in a patient with cholelithiasis on post-therapeutic scan

A 71-year-old male patient was diagnosed with papillary carcinoma follicular variant after bilateral total thyroidectomy and radioactive iodine treatment was applied. The post-therapeutic whole-body scan demonstrated a focal 131I uptake in the right lobe of the liver in the right upper quadrant of the abdomen. Single-photon emission computed tomography/computed tomography (SPECT/CT) was performed to determine the precise localization of 131I uptake. It was understood that the identified focal 131I activity was due to cholelithiasis. In the same period, free-floating gallstones in the lumen and the gallbladder neck were observed on the abdominal ultrasonography

18F-FDG PET/CT concurrent with first radioiodine post-therapeutic scan in high risk differentiated thyroid cancer: a useful tool or just an expensive diversion?

Aim of the present study was to evaluate the clinical impact of fluorine-18F-fluorodeoxyglucose PET/CT (18F-FDG-PET/CT) concurrent with post-therapeutic whole-body radioiodine scan (TxWBS) after first radioiodine (RAI) treatment in patients with high-risk differentiated thyroid carcinoma (DTC). This was a retrospective, single-center study including 39 patients with DTC (22 females, 17 males, median age 54; IQR: 35-60 years, 87% papillary thyroid cancer, 13% follicular thyroid cancer). All patients underwent 18F-FDG-PET/CT and RAI treatment, both performed off L-T4 about 3 months after total thyroidectomy. TxWBS was obtained 3 days afterwards using planar technique and SPECT/CT of neck and thorax regions. Semiquantitative analysis was performed on positive 18F-FDG-PET/CT scans to assess SUV<inf>max</inf>, SUV<inf>ratio</inf>, MTV and TLG values in target lesions (hottest 18F-FDG-positive lesion present in each patient). Receiver operating characteristics (ROC) curve analysis was obtained to establish a cut-off point for SUV<inf>max</inf> able to predict the presence of RAI nonavid lesions. Univariate and multivariate analyses were executed to find out predictive factors for abnormal 18F-FDG-PET/CT imaging. In 11 (28%) patients 18F-FDG-PET/CT and TxWBS were both negative and in 9 (23%) both positive, showing loco-regional or distant metastases. In 14 patients (36%) 18F-FDG-PET/CT showed more lesions than TxWBS, while in 5 (13%) patients more lesions were present at TxWBS than 18F-FDG-PET/CT. Overall, 23 patients (59%) showed 18F-FDG avid lesions and 18F-FDG-PET/TC changed the management in 14 (36%), including the choice to perform RAI therapy with higher activities than expected, lymph-node dissection for loco-regional metastases, direct therapy for solitary bone metastases. Through ROC curve analysis, a value superior to 7.25 of SUV<inf>max</inf> was able to predict the presence of RAI non-avid lesion at TxWBS. Serum stimulated thyroglobulin and extranodal invasion resulted to be risk factors for abnormal 18F-FDG-PET/CT imaging. However, only extranodal invasion turned out to be an independent risk factor for abnormal 18F-FDG-PET/CT. The present study demonstrated the clinical value of RAI-concurrent 18F-FDG-PET/CT in patients with high-risk DTC. However, some questions remain open, including the pretherapeutic thyroglobulin level to use as indication to 18F-FDG-PET/CT and the predictive value of 18F-FDG-PET/CT semiquantitative parameters.

The Diagnostic Usefulness of 131I-SPECT/CT at Both Radioiodine Ablation and during Long-Term Follow-Up in Patients Thyroidectomized for Differentiated Thyroid Carcinoma: Analysis of Tissue Risk Factors Ascertained at Surgery and Correlated with Metastasis Appearance.

131I Single-photon emission computerized tomography/computerized tomography (SPECT/CT) in the management of patients thyroidectomized for differentiated thyroid carcinoma (DTC) was further investigated. Retrospectively, 106 consecutive DTC patients were enrolled at the first radioiodine ablation, 24 at high risk (H), 61 at low risk (L) and 21 at very low risk (VL). 131I whole-body scan (WBS) and SPECT/CT were performed after therapeutic doses using a hybrid dual-head gamma camera. At ablation, SPECT/CT correctly classified 49 metastases in 17/106 patients with a significantly (p < 0.001) more elevated number than WBS which evidenced 32/49 foci in 13/17 cases. In this case, 86/106 patients could be monitored in the follow-up including 13/17 cases with metastases already at post-therapeutic scans. SPECT/CT after radioiodine diagnostic doses more correctly than WBS ascertained disease progression in 4/13 patients, stable disease in other 4/13 cases and disease improvement in the remaining 5/13 cases. Further 13/86 patients with only residues at post-therapeutic scans showed at SPECT/CT 16 neck lymph node (LN) metastases, three unclear and 13 occult at WBS. Significant involvement of some tissue risk factors with metastasis appearance was observed, such as minimal extrathyroid tumor extension and neck LN metastases. These risk factors should be carefully considered in DTC patient follow-up where 131I-SPECT/CT routinely use is suggested as a support tool of WBS.

Neuroendocrine Differentiation and Response to PSMA-Targeted Radioligand Therapy in Advanced Metastatic Castration-Resistant Prostate Cancer: A Single-Center Retrospective Study

Neuroendocrine differentiation is associated with treatment failure and poor outcome in metastatic castration-resistant prostate cancer. We investigated the effect of circulating neuroendocrine biomarkers on the efficacy of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Methods: Neuroendocrine biomarker profiles (progastrin-releasing peptide, neuron-specific enolase, and chromogranin-A) were analyzed in 50 patients commencing 177Lu-PSMA-617 RLT. The primary endpoint was a prostate-specific antigen response in relation to baseline neuroendocrine marker profiles. An additional endpoint was progression-free survival. Tumor uptake on posttherapeutic scans, a known predictive marker for response, was used as a control variable. Results: Neuroendocrine biomarker profiles were abnormal in most patients. Neuroendocrine biomarker levels did not predict treatment failure or early progression (P ≥ 0.13). By contrast, intense PSMA-ligand uptake in metastases predicted both treatment response (P = 0.0030) and reduced risk of early progression (P = 0.0111). Conclusion: Neuroendocrine marker profiles do not predict an adverse outcome from RLT. By contrast, high ligand uptake was confirmed to be crucial for achieving a tumor response.

Temporal changes in MRI appearance of the prostate after focal ablation.

The purpose of our study was to retrospectively evaluate and categorize temporal changes in MRI appearances of the prostate in patients who underwent focal therapy with MRI follow-up. The Institutional Review Board approved this retrospective study and waived the requirement for informed consent. Thirty-seven patients (median age 61; 48-70years) with low-to-intermediate-risk, clinically organ-confined prostate cancer underwent focal ablation therapy from 2009 to 2014. Two radiologists reviewed post-treatment MRIs (n = 76) and categorized imaging features blinded to the time interval between the focal therapy and the follow-up MRI. Inter-reader agreement was assessed (kappa) and generalized linear regression was used to examine associations between an imaging feature being present/absent and days between ablation and MRI. Inter-reader agreement on MRI features ranged from fair to substantial. Edema was found present at earlier times after ablation (median 16-25days compared to MRIs without edema, median 252-514days), as was rim enhancement of the ablation zone (18-22.5days vs. 409-593days), a hypointense rim around the ablation zone on T2-weighted images (53-57.5days vs. 279-409days) and the presence of an appreciable ablation cavity (48.5-60days vs. 613-798days, all p < 0.05). Enhancement of the ablation zone/scar (553-731days vs. 61.5-162days) and the formation of a T2-hypointense scar were found to be present on later MRI scans (514-553days vs. 29-32days, one reader). The MRI appearance of the prostate after focal ablation changes substantially over time. Identification of temporal patterns in the appearance of imaging features should help reduce image interpretation variability and errors when assessing post-therapeutic scans.

Hair Artifact on the Left Side of Head Mimicking Metastasis of Thyroid Carcinoma in a Woman after I-131 Therapy

Accurate interpretation of radioiodine whole body scan is extremely crucial to avoid unwarranted radioiodine ablative therapy in patients with differentiated thyroid carcinoma. We reported a rare case of special hair artifact due to Nocturnal Driveling in a 32-year-old woman on post-therapeutic scans which showed a crescent intense activity in left lateral head, like neo-appeared metastasis. Additional projections after the hair was moved aside demonstrated that the activity was caused by hair contamination, likely from sialorrhea during sleep. The report enriches artifacts on radioiodine scans

Clinical significance of diffuse hepatic uptake on post-therapeutic early and delayed (131)I scan in differentiated thyroid cancer: a preliminary report.

The purpose of this study was to investigate the clinical significance of diffuse hepatic uptake on post-therapeutic early and delayed (131)I scan in patients with differentiated thyroid cancer (DTC). We retrospectively analyzed 219 DTC patients who underwent high-dose (131)I treatment and subsequent post-therapeutic dual (131)I scan. Both early (third day after (131)I treatment) and delayed (5-6th day after (131)I treatment) (131)I scan images were visually assessed and diffuse hepatic uptake was scored using a 4-point grading system depending on intensity. On early (131)I scan, 73 patients (33.4 %) showed diffuse hepatic uptake, while 191 patients (87.2 %) patients showed diffuse hepatic uptake on delayed scan (p < 0.0001). The serum levels of ALT in patients with diffuse hepatic uptake on early scan were higher than those without diffuse hepatic uptake on early scan (p = 0.03 for ALT and p = 0.08 for AST). The serum levels of ALT and AST trended with the grade of hepatic uptake on delayed scan (p = 0.03 for ALT and p = 0.05 for AST). Diffuse hepatic uptake on early or delayed scan showed no significant relationship in the presence of thyroid remnants, metastatic DTC lesions, tumor recurrence during follow-up, and the serum thyroglobulin level (p > 0.05). On logistic regression analysis, both serum ALT (p = 0.01) and AST (p = 0.04) levels were significant predictive factors for diffuse hepatic uptake on early scan, while only serum ALT (p = 0.01) level was significant predictive factor for diffuse hepatic uptake on delayed scan. The frequency of diffuse hepatic uptake on the delayed scan was significantly higher than the early scan. Diffuse hepatic uptake on early post-therapeutic scan and the intensity of diffuse hepatic uptake on delayed scan showed significant correlation with the serum levels of hepatic enzymes, but no significant association in the presence of thyroid remnants, metastatic DTC lesions, and tumor recurrence during follow-up. The timing and intensity of diffuse hepatic uptake on post-therapeutic scan may be related with factors such as hepatic function other than the thyroid tissue or DTC.

A randomized equivalence trial to determine the optimum dose of iodine-131 for remnant ablation in differentiated thyroid cancer

We conducted a stratified randomized equivalence/noninferiority trial from January 2001 to December 2006 to determine whether lower administered activities are as effective as 3.7 GBq (100 mCi) of iodine-131 (I) for remnant ablation. The sample size was found to be 450 on the basis of 80% power (α=5%) and noninferiority margin (δ=0.15). We used an allocation ratio of 2 : 2 : 1 for the 0.93, 1.85, and 3.7 GBq (25, 50, and 100 mCi) groups, respectively. Randomization with concealment was followed for patient group allocation. All patients underwent preablation I whole-body scan, 48-h radioiodine neck uptake measurements and post-therapeutic scans. The patients were advised suppressive L-thyroxine therapy (2 µg/kg/day). Repeat evaluation was performed after 6 months, along with thyroglobulin and antibody assays. The criteria for ablation were as follows: major criterion - negative I whole-body scan; minor criteria - 48-h radioiodine neck uptake less than or equal to 0.2% and stimulated thyroglobulin less than or equal to 10 ng/ml. A total of 422 patients who fulfilled the inclusion criteria (360 papillary and 62 follicular) could be recruited. As per AJCC, 6th ed., we had 70, 11, and 19% of patients in stage I, II, and III, respectively. First-dose ablation was 81.5, 84.9, 88.5, and 84.2% in the 0.93, 1.85, and 3.7 GBq groups and overall, respectively. Histology had no effect on ablation rate. The equivalence testing of the hypothesis was conducted between the 0.93 and 3.7 GBq groups, the 1.85 and 3.7 GBq groups, and the 0.93 and 1.85 GBq groups. Results showed that, at a significance level of 5%, the null hypothesis was rejected for each pair. First-dose I ablation rates at 6 months with 0.93, 1.85, and 3.7 GBq of I are equivalent with the prespecified clinically acceptable noninferiority margin. We conclude that we are probably administering too much I for remnant ablation (trial registration number: CTRI/002291).

Head orthesis therapy in infants with unilateral positional plagiocephaly: an interdisciplinary approach to broadening the range of orthodontic treatment

Unilateral positional plagiocephaly is the most common deformity of the head in infants. As part of a prospective controlled clinical study, the pathomorphology of the positional plagiocephaly in early infancy was examined. The goal was to use noninvasive three-dimensional (3D) imaging to generate, for the first time ever, a standard database of infants without head deformities, to quantify the asymmetry of the positional plagiocephaly, and to evaluate the effectiveness of functional growth control using head orthesis. In the present study, 3D soft-tissue data of the entire head were collected from a total of 40 infants: 20 with positional plagiocephaly (6.0 ± 0.97 months) and 20 infants without a head deformity (6.4 ± 0.3 months). Functional growth was controlled using a custom-made head orthesis. To evaluate the therapy, pre- and posttherapeutic scans were evaluated in three dimensions. Compared with the control group, infants with positional plagiocephaly demonstrated a reduced maximum length of the head, an increased head height, a shift in the ear axis as well as asymmetric anterior and posterior volumes of the neurocranium in lateral comparisons. Therapy using head orthesis led to a significant improvement of the asymmetry, with a reduction of the diagonal difference and an adjustment of the posterior volumes. Conservative growth control of extrinsically deformed infant skulls represents an interdisciplinary medical expansion of the orthodontic therapeutic spectrum. To prevent potential effects of positional plagiocephaly on the viscerocranium, head orthesis therapy is advisable in infancy.

‘Reverse discordance’ between 68Ga-DOTA-NOC PET/CT and 177Lu-DOTA-TATE posttherapy scan

In this technical note, an unusual discordance between diagnostic and posttherapeutic scan resulting from the use of different somatostatin receptor ligands in two settings is described. Such observation, we believe, is multifactorial, but most importantly arises due to different receptor affinity profile of the ligands and different somatostatin receptor subtype expression in different tumors. It is important for the treating physician to be aware of this phenomenon that would aid in improving our understanding of complex ligand-receptor interactions in various somatostatin receptor-positive tumors with its possible implications for therapeutic decision making with radiolabeled somatostatin receptor analogues.

Differentiated thyroid cancer – 2009

Three years ago continental guidelines were published referring management and follow-up of low risk thyroid cancer patients. The aim of this paper is to summarize the changes and new directions in this field. High risk patients require another protocol. Neck ultrasound plays important role in differential diagnosis and in detecting recurrences. Some new ultrasound techniques are discussed, too. FDG-PET can help to solve the problem of patients having negative scan and increased thyroglobulin level. In recent years there was an expansion of our knowledge about the pathomechanism of thyroid cancer. It appears that genetic alterations frequently play a key role in carcinogenesis. There are molecular methods that allow the detection of these genetic events in thyroid fine needle aspirations samples providing important information for diagnosis, management and prognosis. Instead of diagnostic whole body scanning the posttherapeutic scan became preferable but in high risk cases the diagnostic whole body scintigrams serve useful data. Primary therapy of thyroid cancer is an adequate surgery: total thyreoidectomy and, if necessary, lymph node dissection or limited surgery in selected cases. Nowadays radioguided surgery can help to improve the results. Radioiodine therapy (e.g. rest ablation) proved to be a safe and effective method to complete surgery. It can prevent relapses and results in longer survival. Thyroid hormone withdrawal or recombinant human thyrotropin stimulation can increase thyrotropin level before radioiodine treatment. These two methods have similar success rate of rest ablation but irradiation burden of blood is lower in the case of exogenous stimulation which avoids hypothyroid state and preserves quality of life. Since tumor cells fail to maintain the ability to perform physiological functions they undergo dedifferentiation. Therefore, an important aim is to reactivate some function of differentiated cells, e.g. iodine uptake, production of thyroperoxydase and thyroglobulin. Opportunities for this therapeutic effort are also mentioned. Restoration of iodine uptake enables radioisotope treatment. Until now there has been little interest in the development of new drugs for the treatment of thyroid cancer. However, advances in our understanding of tumor cell biology will lead to a paradigm shift in the therapy that is likely to benefit patients who have high risk disease and who do not almost have any therapeutic option. There are new drugs in clinical trials that appear to be more effective than earlier cytotoxic agents. Probably modern chemotherapy of advanced thyroid cancer will have significant results in the near future.

Appropriate Time for Post-Therapeutic I-131 Whole Body Scan

Iodine metabolism and kinetics in thyroid carcinoma cells may be different from that in normal thyroid tissue. The optimal time for performing post-therapeutic scans to detect metastatic lesions is still controversial.We retrospectively analyzed the images of 239 patients who received I-131 therapy at our hospital from January 2006 to May 2008. The therapeutic dose ranged from 1.1 GBq (30 mCi) to 7.4 GBq (200 mCi) and the patients received 3 sequential whole body scans on the third to fourth day, fifth to sixth day, and 10th-11th day after I-131 administration. We scored the I-131 avid lesions by visual assessment into 3 grades: 2=clearly visible; 1=visible; and 0=not visible. We also compared the thyroglobulin levels and FDG uptake among the lesions with probably different kinetics of iodine metabolism.In this study, there was a trend of decreasing visualization of lesions in the sequential images. Twenty-eight percent of lymph node metastases, 17% of lung metastases, and 16% of bone metastases were missed on the late images on 10-11th day. On the other hand, only 5% of the remnants were missed. The ratio of early washout was different between remnants and metastatic lesions. The serum thyroglobulin levels and FDG uptake did not correlate with early washout of the I-131 avid lesions. We concluded that earlier imaging is necessary for detection of metastatic lesions.

What role for recombinant human TSH in the treatment of metastatic thyroid cancer?

The introduction into clinical practice of recombinant human thyroid-stimulating hormone (rhTSH) has marked a turning point in the management of patients with differentiated thyroid cancer. RhTSH offers a safe and reliable alternative to thyroid hormone withdrawal by avoiding both the clinical consequences of hypothyroidism, with a positive impact on quality of life and work productivity, and the potential risk of cancer growth due to a long-lasting endogenous TSH stimulation. In the follow-up of thyroid cancer patients, rhTSH stimulated thyroglobulin is now routinely proposed as it has been shown to be as sensitive as endogenously stimulated thyroglobulin for the detection of residual and metastatic cancer [1]. More recently, the use of rhTSH has been approved for the preparation of adult low-risk patients for postsurgical radioiodine ablation of thyroid remnants with 3.7 GBq I [2]. Although the activity necessary to achieve a comparable rate of ablation is probably higher than that required under hypothyroidism [3, 4], the use of rhTSH is associated with a lower whole-body radiation exposure [5] and allows a shorter hospitalization length, which partially compensates for its cost [6]. The use of rhTSH in the treatment of metastatic thyroid cancer is much more controversial. Although rhTSH has not been formally approved so far for this indication, it has been used off-label since the 1990s to treat patients in which thyroid hormones could not be stopped [7]. This includes patients unable to raise an adequate endogenous TSH response, either because of hypopituitarism or continued production of thyroxine by a thyroid remnant or metastatic tumour, and patients in poor condition due to advanced disease. The results obtained in some patients are encouraging. One may raise the question whether a wider use of rhTSH can be advovated in the therapeutic setting. In our opinion, both clinical and biological data from the literature argue against a more liberal use of rhTSH for the therapy of metastatic thyroid cancer. First, tumour cells of thyroid cancer have a reduced expression of most thyroid-specific genes, including the TSH receptor and the Na/I symporter (NIS) gene [8]. Although the standard two injections protocol of rhTSH provides a high plasma TSH peak, roughly in the range 100–150 mIU/L 24 h after the second injection [9], the concentration increase is short-lived [10]. In order to improve the number of NIS and TSH receptors, and thus enhance the iodine-trapping ability of the cells, a high and prolonged period of TSH stimulation elevation is desirable [11]. Indeed, a I whole-body scan under hypothyroidism is more sensitive than the same scan after rhTSH administration [12]. It should be remembered that a posttherapeutic scan of good quality is an invaluable tool to discover unsuspected metastases and to assess the efficacy of repeated I treatment in metastatic patients [13]. Second, published experience shows that rhTSH stimulates the uptake of radioiodine in metastatic lesions [7]. However, prospective randomized studies comparing the relative efficacy of rhTSH-aided metastatic cancer treatEur J Nucl Med Mol Imaging (2009) 36:883–885 DOI 10.1007/s00259-008-1046-0

Clinical Implications of Diffuse Hepatic Uptake Observed in Postablative and Post-Therapeutic I-131 Scans

Diffuse hepatic uptake of I-131 either on diagnostic or post-therapeutic scans is a usual finding in patients with differentiated thyroid carcinoma. The aim of this study was to evaluate the frequency and clinical significance of diffuse hepatic uptake of radioiodine on post-therapeutic (PT) and postablative (PA) whole-body scans.A total of 720 PA and 172 PT I-131 scans in a total of 732 patients with differentiated thyroid carcinoma were retrospectively reviewed. Residual thyroid tissue and diffuse liver uptake of I-131 were classified from 0 to 4. The correlation between the liver and thyroid remnant uptake score, dose of radioiodine, serum thyroglobuline (Tg), liver function test levels (ALT, AST), liver ultrasonography, presence of metastatic foci, and recurrent disease were examined.Diffuse hepatic uptake was observed in 701 of 722 (94.2%) PA and 162 of 172 (97%) PT whole body I-131 scans. Hepatic radioiodine uptake was positively correlated with the dose of administered I-131 and increased levels of serum AST and ALT. Liver uptake scores of patients with hepatosteatosis were significantly higher than all study groups. However, no evidence of a relationship between diffuse visualization of liver and serum thyroglobulin levels, uptake score of thyroid remnants, presence of local or distant metastatic foci on I-131 scan, and recurrence rate could be demonstrated.The lack of correlation between hepatic radioactive iodine (RAI) uptake and Tg levels, functioning metastatic tissue or thyroid remnants suggests that this finding may be related to factors other than thyroid tissue. The positive correlation between administered RAI dose, hepatic enzymes and hepatosteatosis support the conclusion that diffuse hepatic RAI uptake may be related to different mechanisms as well.

Feasibility of High Activity Rhenium-188-Microsphere in Hepatic Radioembolization

This paper describes the feasibility of intra-arterial high-activity administration of (188)Re-microspheres. Patients with unresectable colorectal liver metastases or hepatocellular cancer (HCC) received single treatments with (188)Re-microspheres. The administered activity was calculated to give a liver dose of 100 Gy. From post-therapeutic scans and urine sampling, the dose to the liver, metastases and bladder was calculated. Toxicity was assessed up to 3 months after administration by means of the Common Terminology Criteria for Adverse Events v3.0 (Trotti et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003;13(3):176-81). Response was evaluated on CT. 13.6 +/- 4.7 GBq (188)Re-microspheres was administered selective in the feeding artery of the tumour to 10 patients (3 x HCC and 7 x colorectal liver metastases). There was a low urinary excretion rate of 8.9 +/- 3.8% of administered activity within 96 h. The absorbed dose to the tumour, normal liver (excluding the tumour) and bladder was 10.24 +/- 5.02 Gy/GBq (128 +/- 47 Gy), 3.94 +/- 2.52 Gy/GBq (50 +/- 33 Gy) and 0.27 +/- 0.20 Gy/GBq (2.4 +/- 1.9 Gy), respectively. There was an acceptable rate of toxicity in 30% of grades I and II, respectively, and 10% with grade III. There was reversible in the most patients within 14 days after treatment. The response was assessed on CT: two patients had a partial response (PR), five patients had stable disease and three patients had disease progression. Treatment of colorectal liver metastases or HCC using high activities of (188)Re-microspheres was well tolerated and a PR was seen in 2 of 10 patients. The treatment represents a therapeutic option in these patients.

A case of stunning of lung and bone metastases of papillary thyroid cancer after a therapeutic dose (3.7 GBq) of131I and review of the literature: implications for sequential treatments

Thyroid stunning is usually defined as the inhibition or suppression of iodide trapping by remnant thyroid tissue or by functioning metastases following a diagnostic dose of 131I. The risk of stunning increases progressively with larger doses. Because the threshold above which this effect occurs in thyroid remnants seems to be between 37 MBq and 111 MBq of 131I, therapeutic 131I doses of 3.7 GBq may cause stunning. We describe stunning of papillary thyroid cancer lung and bone metastases after a therapeutic dose of 131I (3.7 GBq). A T1 bone metastasis and bilateral lung metastases were diagnosed by post-therapeutic dose whole-body scan. Nuclear MRI detected another lesion at T4, whose 131I fixation was not obvious. An additional 0.7 GBq were given after recombinant TSH, 37 days after the therapeutic dose; 24 h later, uptake by the lung and T1 metastases had disappeared, but trapping was again seen 6 months later on the post-therapeutic scan. This re-appearance is evidence in favour of the transitory and reversible character of stunning, and confirms its correspondence to the decreased ability of viable thyroid cells to trap iodine and not to their destruction. A better understanding of stunning would make it possible, in the event of rapidly progressing disease and in conjunction with recombinant thyroid stimulating hormone (TSH), to give several therapeutic doses of 131I in close succession without each dose hampering the effectiveness of the subsequent one.