Purushottam Kand

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.

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.

'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.

Gratifying clinical experience with an indigenously formulated single-vial lyophilized HYNIC-TOC kit at the radiopharmaceutical division of BARC: a pivotal boost for building up a peptide receptor radionuclide therapy programme in an Indian setting

Dear Sir, Peptide receptor radionuclide therapy (PRRT) with Lubased somatostatin receptor analogues has seen a rapid expansion and has generated significant interest over recent years amongst the nuclear medicine fraternity. In India, this has received a major boost in recent years. The primary impetus for this could be ascribed to two developments as a part of radiopharmaceutical research in the country’s premier atomic energy establishment Bhabha Atomic Research Centre (BARC): (1) the availability of Lu-LuCl3 at a much lower cost due to indigenous production (less than one-third of commercially available material) and (2) indigenous production of a single-vial kit for the formulation of Tc-HYNIC-TOC, which has played an important role in centres that do not have access to a germanium/gallium generator. Both these developments at the Radiopharmaceutical Division of BARC could be considered major societal contributions to radiopharmaceutical research in this country in recent years that has benefited a large number of patients with neuroendocrine tumours of various subtypes, both from a diagnostic and a therapeutic standpoint, in multiple clinical centres active in this domain. A single-vial kit formulation for the preparation of TcHYNIC-TOC has been described byGuggenberg et al. [1]. This kit allows a simple method for the preparation of up to two patient doses (10 – 15 mCi, 370 – 555 MBq, per adult patient) of Tc-HYNIC-TOC. Considering a higher cancer patient population density per centre in India, a single vial kit capable of providing up to four patient doses was thought to be more appropriate and was therefore formulated. The lyophilized kit developed in BARC contained 33 μg of HYNIC-TOC, 10 mg of ethylenediaminodiacetic acid, 20 mg of tricine, 40 μg SnCl2, 4.5 mg of sodium phosphate dibasic and 1 mg of sodium phosphate monobasic as ingredients. A significant modification in the present kit was the inclusion of the appropriate buffer which takes care of the final pH of the formulation. This avoids the need for the addition of buffer solution to the kit vial by the user, as is necessary with some of the commercial kits. No deterioration in radiochemical purity (RCP) of Tc-HYNICTOC was observed due to this modification. This kit also allowed relaxation in the maximum volume of Tcpertechnetate that can be added to the kit vial which is restricted to 1 ml in commercial kits. The volume restriction makes commercial kits economically less tenable when the activity per millilitre of the generator eluate goes below the recommended maximum activity for the kit formulation. BARC kits can be reconstituted with 1 – 3 ml of Tc-pertechnetate solution containing a maximum of 80 mCi (2,960 MBq) without compromising the RCP (>90 %) of Tc-HYNIC-TOC. This kit can thus be used for the preparation of multipatient doses evenwhen the activity per millilitre in the Mo/Tc generator eluate is as low as 20 – 25 mCi/ml (740 – 925 MBq/ml). At the Radiation Medicine Centre in Mumbai, which deals with patients from all walks of life including many of lower S. Basu (*) : P. Kand :H. Shimpi Radiation Medicine Centre (B.A.R.C), Tata Memorial Centre Annexe, Jerbai Wadia RoadParel Mumbai 400012, India e-mail: drsanb@yahoo.com

Exploring the role of FDG-PET in the assessment of bone marrow involvement in lymphoma patients as interpreted by qualitative and semiquantitative disease metabolic activity parameter

Bone marrow biopsy (BMB) is currently the standard method to evaluate marrow involvement in malignant lymphomas. However, there exist a number of pitfalls in this technique that can have important implications for initial staging, prognostification, and treatment of the disease. The present study was undertaken to investigate the utility of FDG-PET imaging in the detection of bone marrow involvement in untreated lymphoma patients. Forty untreated patients (36 males and 12 females) with either Hodgkins disease (HD) (n = 17) or non-Hodgkins lymphoma (NHL) (n = 31) underwent whole body FDG-PET study for disease evaluation. Bone marrow uptake of FDG was graded as absence or presence of disease activity at marrow sites by qualitative assessment. Semiquantitative analysis involved deriving disease metabolic index (DMI) using the following formula: DMI = SUV max of suitable circular ROI over PSIS or trochanteric region/ SUVmax of similar ROI over adjoining background. Findings of BMB and FDG-PET were compared for final analysis. Eleven out of 17 HD patients (12 males and 5 females) demonstrated concordance between FDG PET findings and BMB reports. Remaining 6 cases showed discordance of FDG-PET demonstrating presence of marrow involvement at marrow sites and uninvolved marrow on BMB. Twenty six of the 31 NHL cases (24 males and 7 females) demonstrated concordance between FDG PET findings and BMB reports. Remaining 5 cases showed discordance of FDG-PET demonstrating presence of marrow involvement at marrow sites and uninvolved marrow on BMB. All the BMB positive patients (2 of HD and 5 of NHL) demonstrated disease activity in bone marrow on FDG-PET study. All patients with absence of disease activity at marrow sites on FDG-PET scan (9 of HD and 21 of NHL) had histology proven uninvolved marrow. The quantitative assessment by DMI showed a mean of > 2.5 in HD and NHL patients at the PSIS region and the trochanteric region bilaterally in cases of bone marrow involvement by the disease. FDG-PET is a useful adjuvant to BMB for the evaluation of bone marrow involvement in lymphoma patients. The disease metabolic index of > 2.5 at the marrow sites can serve as a semiquantitative parameter for such diagnosis on FDG-PET in untreated patients of lymphoma.

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).

AimsThe 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 methodsThe 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. ResultsA 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). ConclusionIn 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.

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.

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.

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.