Santosh Gupta

Renal and Hematological Toxicity in Patients of Neuroendocrine Tumors After Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE

PURPOSE Peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE is an efficient new treatment option in patients with neuroendocrine tumors (NETs), with low risk of toxicity. Since the kidneys are critical organs in PRRT, renal function is known to deteriorate after PRRT. We analyzed the decline in glomerular filtration rate (GFR), increase in serum creatinine (SCr), and changes in hemogram parameters between pretherapy and at least 6 months after last cycle post-therapy with (177)Lu-DOTATATE. METHODS Forty-seven patients with NETs received 2-6 cycles of (177)Lu-DOTATATE, leading to a total renal radiation absorbed dose of 12.5 ± 4.1 Gy. All renal dose estimates were calculated with the help of OLINDA/EXM software. All patients were infused with renal protective amino acids during the administration of the radiopharmaceuticals. In this study, we used GFR that was estimated by in vitro method using (99m)Tc-DTPA and SCr to assess renal toxicity. RESULTS The patients were administered a mean cumulative activity of 20.1 ± 6.74 GBq of (177)Lu-DOTATATE. There was a significant decrease in GFR from 86.8 ± 15.4 mL/1.73 m(2)/min to 66.1 ± 14.5 mL/1.73 m(2)/min and rise in SCr from 0.86 ± 0.19 mg/dL to 1.0 ± 0.2 mg/dL with treatment. Patients with WHO grade 1 renal toxicity (group 2) at baseline demonstrated an increase in SCr that was significantly higher compared with patients with normal baseline creatinine levels (group 1). No serious acute or remote adverse events were recorded. Self-limiting serious hematological toxicity was observed in 2 patients. CONCLUSIONS The decline in renal function as measured by in vitro GFR tends to be of greater magnitude in patients with baseline impaired renal function than in patients with preserved renal function after PRRT. Hematologic toxicity is relatively rare and can be managed conservatively when encountered.

Dual tracer functional imaging of gastroenteropancreatic neuroendocrine tumors using 68Ga-DOTA-NOC PET-CT and 18F-FDG PET-CT: competitive or complimentary?

Objective This study aimed to compare the diagnostic performance of 68Ga-DOTANOC PET/CT with 18F-FDG PET/CT in the patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Patients and Methods Data of 51 patients with definite histological diagnosis of GEP-NET who underwent both 68Ga-DOTA-NOC PET-CT and 18F-FDG PET-CT within a span of 15 days were selected for this retrospective analysis. Sensitivity, specificity, and predictive values were calculated for 68Ga-DOTA-NOC PET-CT and 18F-FDG PET-CT, and results were compared both on patientwise and regionwise analysis. Results 68Ga-DOTA-NOC PET-CT is superior to 18F-FDG PET-CT on patientwise analysis (P < 0.0001). On regionwise analysis, 68Ga-DOTA-NOC PET-CT is superior to 18F-FDG PET-CT only for lymph node metastases (P < 0.003). Although 68Ga-DOTA-NOC PET-CT detected more liver and skeletal lesions compared with 18F-FDG PET-CT, the difference was not statistically significant. In addition, the results of combined imaging helped in selecting candidates who would undergo the appropriate mode of treatment, whether octreotide therapy or conventional chemotherapy Conclusions 68Ga-DOTA-NOC PET-CT seems to be superior to 18F-FDG PET-CT for imaging GEP-NETs. However, their role seems to be complementary because combination of 68Ga-DOTA-NOC PET-CT and 18F-FDG PET-CT in such patients helps demonstrate the total disease burden and segregate them to proper therapeutic groups.

Dosimetric analyses of kidneys, liver, spleen, pituitary gland, and neuroendocrine tumors of patients treated with 177Lu-DOTATATE.

Objectives The aim of this work was to calculate the radiation absorbed dose to kidneys, liver, spleen, pituitary gland, and neuroendocrine tumors (NETs) of patients treated with 177Lu-DOTATATE. Methods We enrolled 61 patients (male/female patients, 40/21) with mean age of 48.1 ± 15.3 years affected by different types of NETs diagnosed with 68Ga-DOTANOC PET-CT and biochemical markers. For radiation protection of kidneys, amino acid mixture (lysine and arginine) was coinfused; 3.7 to 7.4 GBq (100–200 mCi) of 177Lu-DOTATATE was infused to each patient over 30 minutes. Each patient underwent a series of 9 whole-body scans at 30 minutes (prevoid) and 4, 8, 12, 24, 48, 96, 144, and 168 h. The organs included in dosimetric calculation were kidney, liver, spleen, pituitary gland, and NETs. All dosimetric calculations were done using the OLINDA/EXM 1.0 software. Results Physiological uptake of 177Lu-DOTATATE was seen in all patients in kidneys, liver, spleen, and pituitary gland. Radiation absorbed doses were calculated: 0.57 ± 0.09 mGy/MBq for kidneys, 0.27 ± 0.05 mGy/MBq for liver, 1.17 ± 0.14 mGy/MBq for spleen, 0.058 ± 0.011 mGy/MBq for pituitary gland, and 3.41 ± 0.68 mGy/MBq for NETs. Conclusions The maximum cumulative activity of 177Lu-DOTATATE that can be safely administered to a patient within permissible renal threshold in our study was found to be 40 GBq (1100 mCi). However, there are considerable interpatient differences in absorbed doses of all organs requiring individualized dosimetry for optimizing tumor dose.

Diagnosis of Men-I Syndrome on 68Ga-DOTANOC PET-CT and Role of Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE

Abstract MEN-I is a rare genetic disorder classically characterized by a predisposition to tumors of the parathyroid glands, anterior pituitary gland, and pancreatic islet cells. We present a case of MEN-I syndrome diagnosed using predominantly nuclear medicine imaging followed by radionuclide therapy, thus emphasizing the role of nuclear imaging in diagnosing and treating MEN-I.

Papillary carcinoma masquerading as clinically toxic adenoma in very young children.

Abstract Background: Autonomously functioning thyroid nodules (AFTN) are extremely rare in children. Malignancy may be rarely found in hyperfunctioning ‘hot’ nodules in adults. However, there are limited reports of AFTNs in young children presenting as or developing malignancy in future. We report here two young children aged <6 years old at the time of diagnosis as having an AFTN, which eventually turned out to be papillary carcinoma of thyroid (PTC) on follow-up. Patient findings: A 2-month-old baby had a right-sided neck swelling since birth. On examination, the baby had clinical and biochemical features of thyrotoxicosis. On sonography, and subsequently on 99mTc-pertechnetate thyroid scan, a hot nodule was found. Patient was treated with carbimazole for 5 years. In spite of euthyroidism achieved, the nodule continuously grew in size. Thyroid cytology was inconclusive, hence hemithyroidectomy was performed and histopathology turned out to be PTC. Another 5-year-old female child had a large right-sided AFTN on thyroid scan. She was treated with radioiodine; however, like the previous case, the nodule started growing in size. She subsequently underwent near total thyroidectomy and histology was reported as PTC. Conclusion: In the light of this report that shows that solitary hyperfunctioning nodules in very young children have high chance of malignancy, we recommend hemithyroidectomy as the treatment of choice.

Discordance in 68Ga-DOTANOC and 177Lu-DOTATATE uptake in diagnostic and post-therapy scans in patients with medullary thyroid cancer-likely reasons

Sir, We qualitatively studied the discordance between pre-therapy 68Ga-DOTANOC scans and post-therapy 177Lu-DOTATATE scans in patients with medullary thyroid cancer (MTC). Patients with metastatic/recurrent, inoperable MTC showing good uptake of Ga-DOTANOC on positron emission tomography (PET)/computed tomography (CT); >18 years of age with serum creatinine ≤1.3 mg%, bilirubin ≤1 mg%, SGOT, SGPT ≤50 IU; baseline normalized GFR (2 sample method-Tc-DTPA) ≥70 ml/min/1.73 mr, Hb ≥9 gms%, TLC ≥4000/μl, platelets ≥1,50,000/μl were included in this study.

Evaluation of IFN-γ response to rotavirus and non-structural protein NSP4 of rotavirus in children following severe rotavirus diarrhea

BACKGROUND Rotavirus (RV) is the commonest cause of severe gastroenteritis in young children worldwide. However the natural immune mechanisms controlling and preventing rotavirus disease in humans are not fully understood. OBJECTIVE To examine cellular immune responses to whole rotavirus (vaccine strain, 116E) and non-structural protein-4 (116E-NSP4) in children during natural rotavirus-infection. STUDY DESIGN Gamma-interferon (IFN-gamma) responses were evaluated by enzyme-linked immunospot assay in peripheral blood mononuclear cells from children with RV (n=26) or non-RV (n=10) gastroenteritis and from RV-exposed adults (n=10). Additionally, IL-4 responses were assessed in 5 of the 10 adults and 6 of 26 RV-infected children. RESULTS IFN-gamma secreting cells specific to whole RV were detected in 68% of RV-positive children and to NSP4 in 43% of these children between 4 and 30 days of illness onset. IFN-gamma responses were transient and were found higher in RV-exposed adults than in children (P<0.05). Within the RV-positive group, IFN-gamma responses in children with prior RV-exposure were higher than children without prior exposure (P<0.05). The response to whole RV and NSP4 were positively correlated (P<0.01, r(s)=0.66). CONCLUSIONS Significant IFN-gamma responses to rotavirus candidate vaccine strain 116E were detected in children during natural RV-infection and in RV-exposed adults. Significant IFN-gamma responses to NSP4 were also observed in these study groups.

68Ga-DOTA-NOC PET and peptide receptor radionuclide therapy in management of bilateral ovarian metastases from gastrointestinal carcinoid.

The management of neuroendocrine tumours is challenging when curative surgery is ruled out because of distant metastases. We report a case of gastrointestinal carcinoid with bilateral ovarian metastases in a 50-year-old female who received octreotide therapy followed by peptide receptor radionuclide therapy and surgery thereafter. Somatostatin receptor expression on neuroendocrine tumours has implications in diagnosis and therapy. (68)Ga-DOTA-NOC PET is a recent advancement in the field of somatostatin receptor imaging. The lesions which demonstrate tracer uptake on positron emission tomographic studies can be further planned for treatment with octreotide and (177)Lu-DOTA-TATE. The case in discussion responded well to non-invasive treatment options before proceeding to definitive surgical management.

Peptide Receptor Radionuclide Therapy With 177Lu DOTATATE in a Case of Recurrent Carotid Body Paraganglioma With Spinal Metastases

Paragangliomas are rare benign neuroendocrine tumors, and 80% of all paragangliomas are either carotid body tumors or glomus jugulare tumors. We present a case of recurrent unresectable carotid body paraganglioma with nodal and T7 vertebral metastases in a 30-year-old man 6 years postsurgery detected with Ga DOTANOC PET/CT and was administered with peptide receptor radionuclide therapy using Lu DOTATATE. After 5 cycles of Lu DOTATATE (total cumulative activity of 750 mCi [27 GBq]), significant response at the primary site on Ga DOTANOC PET/CT and complete disappearance of nodal and T7 vertebral metastases were noted.

Preliminary Experience with Yttrium-90-labelled Rituximab (Chimeric Anti CD-20 Antibody) in Patients with Relapsed and Refractory B Cell Non-Hodgkins Lymphoma

BACKGROUND AND OBJECTIVES The aim of the study is to evaluate the therapeutic efficacy and safety of Yttrium- 90 radiolabelled chimeric anti CD20 antibody-Rituximab in the treatment of patients with relapsed/ refractory B cell Non-Hodgkins Lymphoma (NHL). METHODS Twenty patients with relapsed/refractory CD20+ NHL in progressive state were included in the study. These patients had undergone a median of 2 (range 2-5) prior standard chemotherapy ± immunotherapy regimens. All the patients received rituximab 250 mg/m2 on days 1 and 8, and either 14 MBq/kg (0.4 mCi/kg) or 11 MBq/kg (0.3 mCi/kg) of Y-90 Rituximab on day 8 (maximum dose, 32 mCi) depending upon their platelet count. The patients were observed for systemic toxicity and response for at least 12 weeks after therapy. RESULTS No acute adverse effects were observed after the administration of 90Y-Rituximab. Overall response rate (ORR) was 45% of which complete response (CR) was observed in 2 patients, stable disease in 1 patient and partial response in 6 patients. The therapy was well tolerated with grade IV thrombocytopenia, neutropenia and anemia observed in 3, 4 and 2 patients respectively. CONCLUSION 90Y-Rituximab therapy is safe and well tolerated in high risk extensively pretreated NHL patients. Toxicity is primarily hematologic, transient and reversible.