Comparative evaluation of iodine-131 metaiodobenzylguanidine and 18-fluorodeoxyglucose positron emission tomography in assessing neural crest tumors: Will they play a complementary role?

BACKGROUND: 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) has established a role in the evaluation of several malignancies. However, its precise clinical role in the neural crest cell tumors continues to evolve. PURPOSE: The purpose of this study was to compare iodine-131 metaiodobenzylguanidine (131I-MIBG) and FDG-PET of head to head in patients with neural crest tumors both qualitatively and semiquantitatively and to determine their clinical utility in disease status evaluation and further management. MATERIALS AND METHODS: A total of 32 patients who had undergone 131I-MIBG and FDG-PET prospectively were evaluated and clinicopathologically grouped into three categories: neuroblastoma, pheochromocytoma, and medullary carcinoma thyroid. RESULTS: In 18 patients of neuroblastoma, FDG PET and 131I-MIBG showed patient-specific sensitivity of 84% and 72%, respectively. The mean maximum standardized uptake value (SUVmax) of primary lesions in patients with unfavorable histology was found to be relatively higher than those with favorable histology (5.18 ± 2.38 vs. 3.21 ± 1.69). The mean SUVmaxof two common sites (posterior superior iliac spine [PSIS] and greater trochanter) was higher in patients with involved marrow than those with uninvolved one (2.36 and 2.75 vs. 1.26 and 1.34, respectively). The ratio of SUVmaxof the involved/contralateral normal sites was 2.16 ± 1.9. In equivocal bone marrow results, the uptake pattern with SUV estimation can depict metastatic involvement and help in redirecting the biopsy site. Among seven patients of pheochromocytoma, FDG-PET revealed 100% patient-specific sensitivity. FDG-PET detected more metastatic foci than 131I-MIBG (18 vs. 13 sites). In seven patients of medullary carcinoma thyroid, FDG-PET localized residual, recurrent, or metastatic disease with much higher sensitivity (32 metastatic foci with 72% patient specific sensitivity) than 131I-MIBG, trending along the higher serum calcitonin levels. CONCLUSIONS: FDG-PET is not only a good complementary modality in the management of neural crest cell tumors but also it can even be superior, especially in cases of 131I-MIBG nonavid tumors.

Effect of l-Thyroxine on Micronuclei Frequency in Peripheral Blood Lymphocytes in Clinical and Experimental Conditions.

The aim was to study the genotoxic effect of high concentration of thyroxine (T4) in vivo in peripheral blood lymphocytes (PBL) of the patients suffering from thyroid disorders. The effect was compared by performing in vitro experiments with addition of increasing concentration of T4 (0.125-1 µM) in whole blood samples from healthy donors. Cytokinesis-blocked micronuclei (CBMN) assay method was used to assess the DNA damage in the PBL. The study included 104 patients which were grouped as control (n = 49), hyperthyroid (n = 31) and hypothyroid (n = 24). A significant increase in micronuclei (MN) frequency was observed in hyperthyroid patients when compared with the hypothyroid and euthyroid group thereby suggesting increased genotoxicity in hyperthyroidism (p < 0.001). A significant increase in MN frequency was observed at T4 concentration of 0.5 µM and above when compared to lower T4 concentrations (0.125 and 0.25 µM) and basal in in vitro experiments (p = 0.000). The results indicate that the T4 in normal concentration does not exhibit the genotoxic effect, as observed in both the in vivo and in vitro experiments. The toxicity of T4 increases at and above 0.5 µM concentration in vitro. Therefore acute T4 overdose should be handled promptly and effectively so as to avoid the possible genotoxic effect of high concentration of T4 in vivo.

Value of 18F-FDG PET negativity and Tg suppressibility as markers of prognosis in patients with elevated Tg and 131I-negative differentiated thyroid carcinoma (TENIS syndrome).

AIMS: The aim of the study was to investigate the prognostic value of fluorine-18 fluorodeoxyglucose (18F-FDG) PET negativity and thyroglobulin (Tg) suppressibility in differentiated thyroid carcinoma patients with elevated Tg and a negative radioiodine scan. MATERIALS AND METHODS: The study population was selected from thyroid cancer patients registered at a large tertiary cancer care center for management and consisted of patients with metastatic thyroid cancer with elevated Tg on follow-up, negative 131I whole-body scan and negative 18F-FDG PET/computed tomography (CT) study. Patients with thyroid carcinoma were subjected to a thyroid-stimulating hormone-stimulated assessment on the basis of a 131I whole-body scan, serum Tg level and whole-body 18F-FDG PET/CT scan for evaluation of metastatic disease burden. The same patients were subjected to a follow-up evaluation of serum Tg and whole-body 18F-FDG PET/CT scan under thyroid-stimulating hormone suppression while on thyroxine sodium. Comparison was also made between the findings of 18F-FDG PET/CT in patients demonstrating suppressible Tg. RESULTS: A total of 40 (25 male and 15 female) patients were included in the study. All patients had a negative whole-body 18F-FDG PET/CT study but had stimulated Tg more than 5 ng/dl (range: 5.1-> 250 ng/ml), indicating the presence of disease. The patients demonstrated variable Tg suppressibility and were classified on the basis of the extent of Tg suppressibility (%Tg suppressibility > 90% in 21 patients; %Tg suppressibility 65-90% in 12 patients; and %Tg suppressibility < 65% in five patients; and no suppressibility in two patients). 18F-FDG PET was normal in all of these patients both on stimulation and on suppression. All patients were asymptomatic during this period. No definite correlation could be established between the status of metastasis or the histopathology and suppressibility of Tg. The average follow-up data available were for more than 3 years in 26 patients (two patients had no Tg suppressibility in this group), for 1-3 years in 10 patients and for less than 1 year in four patients. At the time of analysis in this study the patients were asymptomatic during the aforementioned follow-up periods (based upon follow-up data available). CONCLUSION: In this study, we observed that 'elevated Tg but normal 18F-FDG PET' exists as a definitive entity in differentiated thyroid carcinoma. On the basis of the studied follow-up, a negative 18F-FDG PET in the setting of elevated Tg level could be regarded as a favorable prognostic indicator to predict symptom-free status during the follow-up period in this group of patients. Suppressibility of Tg (> 65%) is observed in a significant fraction of these patients, which appears to be independent of the status of metastasis or the histopathology. Also patients who show no Tg suppressibility but had a negative 18F-FDG PET/CT scan still had a better prognosis indicated by the disease-free interval in these patients as indicated in our study. Whether there exists any relation between the extent of suppressibility and their long-term outcome requires to be further examined in future prospective studies.

Enhanced myocardial fluorodeoxyglucose uptake following Adriamycin-based therapy: Evidence of early chemotherapeutic cardiotoxicity?

AIM: To analyze changes in myocardial glucose metabolism using fluorodeoxyglucose (FDG)-positron emission tomography (PET) in patients treated with adriamycin and to investigate the clinical significance of these changes. METHODS: Considering that FDG-PET scanning has the ability to show changes in glucose metabolism in the myocardium, we retrospectively analyzed the FDG-PET studies of 18 lymphoma patients treated with adriamycin-based chemotherapy in both the pre- and post-therapy setting. Cardiac contractile parameters such as left ventricular ejection fraction were not available for correlation in all patients due to the short duration and the level of cumulative dose administered in these patients during the time of the follow-up FDG-PET study. The change in myocardial glucose utilization was estimated by change in standard uptake values (SUV) in the myocardium. RESULTS: We observed a significant change in SUVmean values in the myocardium (defined as more than ± 20% change in cardiac SUVmean between pre- and post-chemotherapy PET) in 12 patients, whereas 6 patients did not show any significant cardiac FDG uptake in both pre- and post-therapy PET scans. Patients were divided into three groups based on the changes observed in myocardial tracer uptake on the follow-up (18)F-FDG-PET study. Group A (n = 8): showed an increase in cardiac (18)F-FDG uptake in the post-therapy scan compared to the baseline scan carried out prior to starting adriamycin-based chemotherapy. Group B (n = 6): showed no significant cardiac (18)F-FDG uptake in post-therapy and baseline PET scans, and group C (n = 4): showed a fall in cardiac (18)F-FDG uptake in the post-therapy scan compared to the baseline scan. Mean cumulative adriamycin dose (in mg/m(2)) received during the time of the follow-up FDG-PET study was 256.25, 250 and 137.5, respectively. CONCLUSION: Our study shows three different trends in the change in myocardial glucose metabolism in patients undergoing adriamycin-based chemotherapy. A further prospective study with prolonged follow-up of ventricular function is warranted to explore the significance of enhanced FDG uptake as a marker of early identification of adriamycin-induced cardiotoxicity.

Impact of FDG-PET and -PET/CT imaging in the clinical decision-making of ovarian carcinoma: an evidence-based approach.

The most definitive role of fluorodeoxyglucose (FDG)-PET/computed tomography (CT) at present is surveillance and detecting recurrence in patients who have completed primary therapy but demonstrate a rising serum tumor marker (e.g., CA-125 levels). In this scenario, PET/CT demonstrates high sensitivity and accuracy in detecting lesions that are otherwise challenging, and appears superior (with less interobserver variability) compared with CT alone. Despite the fact that peritoneal deposits may be missed by PET/CT, the overall performance is better than CT alone. FDG-PET does not play a significant additional role in the primary diagnosis of ovarian cancers; however, the role of combined PET/CT modality has recently begun to be re-explored for initial disease staging, particularly because PET/CT can pick up small unsuspected lesions and thereby provide a better disease assessment of the whole body in a single examination. The baseline PET/CT also subserves an important role for future monitoring of therapy response. Therapy monitoring by PET could help to optimize neoadjuvant therapy protocols and to avoid ineffective therapy in nonresponders early in its course, although PET/CT has cost-effectiveness issues that need further evaluation. The prognostic value of FDG-PET/CT has been investigated in the following areas: in the preoperative setting to predict optimal cytoreduction; to assess the value of a positive FDG-PET following primary surgery; and when employed as a replacement for second-look laparotomy following completion of primary surgery and chemotherapy. The data, although promising, are still sparse in all the three domains for a definite recommendation.

Myocardial uptake of F-18-fluorodeoxyglucose in whole body positron emission tomography studies.

PURPOSE: The objective of this study was to correlate the degree of myocardial fluorodeoxyglucose (FDG) uptake in routine oncology positron emission tomography (PET) studies with fasting blood sugar level (FBSL), fasting period (FP) and age of the patient. MATERIALS AND METHODS: Ninety-one patients (62 males and 29 females, age range: 7-78 years) with malignant diseases were included in the study. Whole body FDF-PET study was carried out after 1 h of intravenous injection of 296-370 MBq (8-10 mCi) F-18 FDG. Images were interpreted visually and patients were classified into four grades of myocardial uptake: No myocardial uptake = Grade 0; mild uptake = Grade 1; moderate uptake = Grade 2; and Marked uptake = Grade 3. Quantitative analysis was done by calculating Standardized uptake value (SUVmax). Age, FBSL and FP were recorded. RESULTS: Thirty-seven (41%) patients showed no uptake in myocardium (Gr-0). Mean FP, FBSL and age was 14 h, 94.19 mg% and 44.3 years respectively. Eleven (12%) cases were rated as Grade 1, 27 (30%) as Grade 2 and 16 (17%) as Grade 3. The mean values of FP, FBSL and age were 12.9 h, 96.55 mg% and 43.54 years for Grade 1, 13.48 h, 87.11 mg% and 40.85 years for Grade 2 and 13.37 h, 86.56 mg% and 36.18 years for Grade 3 respectively. SUVmax was found to vary between 1 and 22. It was observed that 47% (Grade 2 and 3) patients had significant cardiac FDG uptake in spite of blood sugar levels 71-125 mg%. CONCLUSION: The degree of myocardial FDG uptake did not show significant correlation with FBSL, FP or age of the patient. Perhaps the reason lies elsewhere like insulin levels, medical treatments, fat metabolism, and myocardium status or some unexplored factors.

A pregnant woman with metastatic papillary thyroid carcinoma and paraplegia: Multiple considerations involved in the management.

A 35 years old primigravida hailing from a humble, rural background with no previous history related to thyroid carcinoma, presented with acute paraparesis at the last trimester of pregnancy and was diagnosed to harbor metastatic papillary thyroid carcinoma (PTC) following magnetic resonance imaging (MRI) of the spine with guided biopsy, which demonstrated near complete collapse of D5 and D10 vertebral bodies with altered signal on the D4 to D6 and D9 to D11 vertebral bodies, in addition to a gravid uterus and a large goiter. There was also evidence of bilateral nodular lesions in the lung parenchyma and a fairly large hepatic lesion in segment 8 of the liver . Histopathology revealed metastatic follicular variant of thyroid papillary carcinoma. This case with challenging presentation had multiple issues to be resolved during its management: a) acute paraparesis and the requirement of radioiodine ((131)I) treatment soon after total thyroidectomy, b) her first valuable pregnancy that required to be managed successfully, c) the poor general condition, d) the abstinence from iodine containing medications, in relation to the Cesarean section planned, e) the timing of total thyroidectomy, f) postnatal care of the newborn and g) radioprotective measures. All were important considerations in the management of this patient. Iodine restricted diet and medications were recommended and were communicated to the obstetricians involved in the patient. The patient underwent Cesarean section and total thyroidectomy at the same sitting. The newborn baby was healthy and was started on artificial feeding. Recombinant TSH primed protocol was not considered immediately in view of a major surgery being undertaken and the poor general condition, so that the patient would not require frequent support during the isolation period. In the first 3 weeks of the postoperative period, she was put on T3 substitution and after a 2 weeks gap was given (131)I and whole body diagnostic scan was undertaken 48h after the administration of (131)I scan dose. Both the diagnostic and post (131)I treatment scan demonstrated multiple foci of (131)I uptake in the skeleton, lungs and liver. Following discharge from the isolation ward, adequate separation from the infant was ensured and the childcare was undertaken by relatives. The patient had a remarkable improvement clinically. During the next 3-½ years she was treated 2 more times with (131)I with cumulative doses of about 25.9GBq. The last post-treatment scan is depicted in. She has been presently ambulatory with complete resolution of paraplegia and a significantly better quality of life without any requirement of support, despite the presence of extensive skeletal disease. A recent review entitled "Approach to the pregnant patient with thyroid cancer", addresses this topic as a separate category. Similar emphasis has also been given by other authors while dealing with these patients. In our experience, patients with PTC metastatic lesions in the vertebrae show better response compared to those with large flat bone metastases likely related to the small size of the former. In conclusion, a teamwork of surgeons, obstetricians, nuclear medicine physicians as well as the strong support by the relatives, was necessary to favorably treat this patient with metastatic PTC, paraplegia and pregnancy.

'Reverse discordance' between 68Ga-DOTA-NOC PET/CT and 177Lu-DOTA-TATE posttherapy scan: the plausible explanations and its implications for high-dose therapy with radiolabeled somatostatin receptor analogs.

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.

Metastatic involvement of the spleen in differentiated carcinoma of thyroid.

Splenic metastasis in differentiated thyroid carcinoma is rare occurrence. We describe an unusual case of diffuse metastatic splenic involvement with normal hematological indices in differentiated thyroid carcinoma demonstrated by post-therapy whole body radioiodine scan.

Micronuclei frequency in peripheral blood lymphocytes of thyroid cancer patients after radioiodine therapy and its relationship with metastasis.

In most cancers peripheral blood lymphocytes exhibit DNA damage. In the case of thyroid cancer the micronucleus (MN) assay has been used to assess DNA damage before and after exposure to iodine-131 ((131)I). The aim of our study was to use this method to assess DNA damage in peripheral blood lymphocytes of thyroid cancer patients and search for its relationship with metastasis as well as (131)I exposure. A significant increase in micronuclei frequency was observed in peripheral blood lymphocytes of 54 thyroid cancer patients in comparison to 38 controls (p=0.000). Further analysis revealed significant elevation in micronuclei index from 48.5 MN/1000 BN cells (range: 25.1-111.2, n=25) in patients without metastasis to 68.1 MN/1000 BN cells (range: 26.2-135.5, n=29, p=0.001) in group of patients with metastasis to one or more sites. There was no clear correlation between the micronuclei frequency and the therapeutic (131)I dose ranging from 0.41 to 31.5 GBq with the exposure interval of <1 to 126 months. In addition, age and sex did not show any influence on micronuclei frequency in either patients or control population. These findings are indicative of increased basal DNA damage in thyroid cancer patients before treatment. Radioiodine treatment did not increase DNA damage measured by the micronuclei frequency for the interval between the last radioiodine dose administered and analysis of blood sample. However a significant increase of peripheral blood lymphocytes micronuclei was observed in thyroid cancer patients with metastasis.

Bronchoalveolar carcinoma of lung masquerading as iodine avid metastasis in a patient with minimally invasive follicular carcinoma of thyroid.

A 52-year-old man with follicular thyroid carcinoma was administered 182 mCi of radioiodine (I-131) a month after total thyroidectomy. Post-therapy scan revealed diffuse uptake of radioiodine in the apical left lung. CT-guided biopsy of this mass revealed mucinous bronchoalveolar carcinoma. Immunohistochemistry for thyroglobulin was negative. An FDG PET scan showed avid uptake in the lung mass. Surgery was ruled out, so he was given chemotherapy, without benefit. The lesion continued to show I-131 uptake even while on daily T3 substitution, suggesting that the mass was thyroid stimulating hormone-independent. Because the mass showed I-131 uptake and chemotherapy was not beneficial, it was decided to treat with I-131. He was continued on T3 substitution therapy and was given 209 mCi of I-131. Follow-up CT scan a few weeks later reported a 1-cm all round reduction of the mass. I-131 scan showed avid tracer uptake in the mass. This case suggests the possibility of this therapeutic option in nonthyroidal tumors that may concentrate radioiodine.