Automated radiochemical synthesis of pharmaceutical grade [18 F]FLT using 3-N-Boc-5'-O-dimethoxytrityl-3'-O-nosyl-thymidine precursor and its Sep-Pak® purification employing selective elution from reversed phase.

Pharmaceutical grade 3'-deoxy-3'-[18 F]fluorothymidine [18 F]FLT was synthesized using 3-N-Boc-5'-O-dimethoxytrityl-3'-O-nosyl-thymidine (BOC-Nosyl) precursor, in the general purpose TRACERlab FX modules. Purification of [18 F]FLT, via solid phase extraction (SPE) after radiosynthesis, using a combination of different SPE cartridges, yielded satisfactory results, with radiochemical and chemical purity >99%. While the non-decay corrected radiochemical yield (RCY) with 20 mg (24 µmole) of BOC-Nosyl precursor was found to be 6.80 ± 0.16%, the decay corrected radiochemical yield (RCY) was 9.95 ± 0.24%. Residual acetone, acetonitrile, and ethanol levels were found to be 22.97 ± 0.76, 109.08 ± 0.93, and 7,666.45 ± 3.7 ppm, respectively. A simplified method for solid-phase purification of [18 F]FLT was developed, circumventing the need for HPLC purification. Biodistribution in C57BL/6 mice with B16F10 cell line-induced melanoma showed tumor to blood ratio of ~3.8 at 90 min. PET/CT imaging of normal rabbit injected with [18 F]FLT shows selective uptake in the bone marrow and small intestine. [18 F]FLT was found to be excreted through the kidneys and get collected in the urinary bladder, 120 min post injection. PET/CT imaging performed in rabbit model at 30, 60, 90, and 120 min post [18 F]FLT injections showed concordance with tissue distribution kinetics of mice tumor model.

Sellar-Parasellar and Petrous Bone Metastasis from Differentiated Thyroid Carcinoma: Imaging Characteristics and Follow-Up Profile Post Radioiodine Therapy.

Sella turcica and petrous bone metastasis from differentiated thyroid carcinoma are rare clinical entities, with only a few limited cases reported to date. Two cases, one of sella turcica metastasis and the other of petrous bone metastasis from carcinoma of the thyroid gland, are presented. The cases diagnosed to have arisen from poorly differentiated thyroid carcinoma and follicular carcinoma of thyroid, respectively, subsequently underwent total thyroidectomy, radioiodine (RAI) scans and RAI therapies with iodine-131, external radiotherapy, and levothyroxine suppression with follow-up. Their clinical symptoms gradually subsided, with reduction in serum thyroglobulin, and finally resulted in disease stabilization. With the multimodality therapeutic approach, both patients are alive to date, with 48- and 60-month survival post diagnosis, respectively.

Suicidal behaviour: What's the brain up to?

BACKGROUND: Individuals with suicidal behaviours are increasingly recognized as having impairments in brain metabolism. However, these are not well delineated. AIM: To evaluate regional cerebral glucose metabolism (rCMglu) in subjects with suicidal behaviours and assess differences in rCMglu between depressed and non-depressed suicidal subjects. METHODS: Thirty-three subjects with suicidal behaviours were assessed using Columbia Suicide Severity Rating scale (CSSRS) and Beck's Depression Inventory (BDI). Brain metabolism was assessed using [18F]Fluoro,Deoxy-Glucose Positron Emission Tomography (FDG-PET). RESULTS: Of 33 subjects, eighteen had depression. FDG-PET findings revealed that in comparison to mean asymptomatic controls, subjects had decreased rCMglu in right inferior frontal, left Broca's, left inferiolateral andsuperiolateral temporal, right inferior parietal and left posterior cingulate cortex. Increased rCMglu was seen in bilateral superior and medial frontal, right inferiolateral and posteriomedial temporal cortex, and midbrain. CSSRS total intensity inversely correlated with rCMglu in medial frontal cortex, left Broca's and superiolateral temporal cortex and directly correlated with rCMglu in right cerebellum. There was no significant difference in rCMglu between depressed and non depressed group. CONCLUSIONS: Significant differences exist in rCMglu of suicidal individuals, chiefly in frontal and temporal regions. Understanding these would help us identify individuals more at risk for suicidal behaviours.

On the Separation of Yttrium-90 from High-Level Liquid Waste: Purification to Clinical-Grade Radiochemical Precursor, Clinical Translation in Formulation of 90Y-DOTATATE Patient Dose.

Introduction: The quality control parameters of in-house-produced 90Y-Acetate from high-level liquid waste (HLLW) using supported liquid membrane (SLM) technology were validated and compared with the pharmacopeia standard. The radiolabeling of DOTATATE yielding 90Y-DOTATATE in acceptable radiochemical purity (RCP), with expected pharmacological behavior in in vivo models, establish the quality of 90Y-Acetate. Clinical translation of 90Y-Acetate in formulation of 90Y-DOTATATE adds support toward its use as clinical-grade radiochemical. Methods: Quality control parameters of 90Y-Acetate, namely radionuclide purity (RNP), were evaluated using ß- spectrometry, γ-spectroscopy, and liquid scintillation counting. RCP and metallic impurities were established using high-performance liquid chromatography and inductively coupled plasma optical emission spectrometry, respectively. The suitability of 90Y-Acetate as an active pharmaceutical ingredient radiochemical was ascertained by radiolabeling with DOTATATE. In vivo biodistribution of 90Y-DOTATATE was carried out in nude mice bearing AR42J xenografted tumor. Clinical efficacy of 90Y-DOTATATE was established after using in patients with large-volume neuroendocrine tumors (NET). Bremsstrahlung imaging was carried out in dual-head gamma camera with a wide energy window setting (100-250 keV). Results: In-house-produced 90Y-Acetate was clear, colorless, and radioactive concentration (RAC) in the range of 40-50 mCi/mL. RCP was >98%. 90Sr content was <0.85 µCi/Ci of 90Y. Gross λ content was <0.8 nCi/Ci of 90Y and no γ peak was observed. Fe3+, Cu2+, Zn2+, Cd2+, and Pb2+ contents were <1.7 µg/Ci. The radiolabeling yield (RLY) of 90Y-DOTATATE was >94%, RCP was >98%. The in vitro stability of 90Y-DOTATATE was up to 72 h postradiolabeling, upon storage at -20°C. Post-therapy (24 h) Bremsstrahlung image of patients with large NET exhibit complete localization of 90Y-DOTATATE in tumor region. Conclusions: This study demonstrates that the in-house-produced 90Y-Acetate from HLLW can be used for the formulation of various therapeutic 90Y-based radiopharmaceuticals. Since 90Y is an imported radiochemical precursor available at a high cost in India, this study which demonstrates the suitability of indigenously sourced 90Y, ideally exemplifies the recovery of "wealth from waste." The Clinical Trial Registration number: (P17/FEB/2019).

Sequential Duo-Peptide Receptor Radionuclide Therapy With Indigenous 90Y-DOTATATE and 177Lu-DOTATATE in Large-Volume Neuroendocrine Tumors: Posttherapy Bremsstrahlung and PET/CT Imaging Following 90Y-DOTATATE Treatment.

The efficacy of Lu-DOTATATE in large neuroendocrine tumors (NETs) is reduced because of the lower energy (Eßmax 0.497 MeV) and shorter range of Lu. The pure ß-emitter Y with its longer ß range is more effective in larger tumors. This should be balanced with the greater risk of Y-DOTATATE-related nephrotoxicity. Sequential duo-peptide receptor radionuclide therapy may result in a better response with minimal adverse effects in large-volume heterogeneous NETs. A 56-year-old man with large rectal NET liver metastases, treated with Y-DOTATATE and Lu-DOTATATE and sequential duo-peptide receptor radionuclide therapy, presented with post-Y-DOTATATE bremsstrahlung and PET/CT in comparison with Ga-DOTATATE PET/CT and Lu-DOTATATE scans.

Clinical Efficacy of Sodium [99mTc] Pertechnetate from Low Specific Activity 99Mo/99mTc Autosolex Generator in Hospital Radiopharmacy Centre.

BACKGROUND: Few nuclear reactors in the world producing high specific activity (HSA) 99Mo using enriched 235U (HEU), are aging and are planned for shut down in the near future. Further, HEU will not be freely available, due to safeguards, and the technology for 99Mo from low-enriched 235U (LEU) is not yet widely accepted since 239Pu contamination in the product is an issue. Production of 99mTc from low specific activity (LSA) 99Mo obtained from 98Mo(n,)99Mo reaction in research reactor and 100Mo(,n)99Mo reaction in accelerator or directly from 100Mo(p,2n)99mTc nuclear reaction in cyclotron, has been explored [1]. The methyl ethyl ketone (MEK) based solvent extraction technique is n well known method for the separation of 99mTc from low specific activity 99Mo. The 99Mo/99mTc autosolex generator [2], a computer controlled automated module, utilizes the conventional MEK solvent extraction method for extraction of 99mTc. Herein, we have validated the usage of autosolex for preparation of pharmacopoeia grade 99mTcO4- from 7.40-27.5 GBq of LSA 99Mo-SodiumMolybdate (99MoO42-) solution and validated the quality of the 99mTcO4- by preparing wide range of 99mTc-radiopharmaceuticals (99mTc-RP). MATERIALS AND METHODS: The 99mTcO4- was extracted from the autosolex as described in [2] starting from 7.40-27.5 GBq of LSA 99MoO42- and subjected to the required physico-chemical and biological quality control (QC) tests. The eluted 99mTcO4- labeled various fourth generation 99mTc radiopharmaceuticals cold kits (99mTc-cold kits) apart from regular 99mTc-cold kits in our centre. Various 99mTc-RP extracted 99mTcO4- using standard procedures [3] were prepared and subjected to required QC as Indian Pharmacopeia monograph [4] and used in scintigraphic imaging in patients. The radiation exposure dose to the operator were compared between autosolex and manual MEK based solvent extraction generator. RESULTS: The extracted 99mTcO4- from autosolex is a clear and colorless solution with pH between 5.0-6.5. The elemental molybdenum (Mo) and aluminum (Al) content <10µg/mL, MEK levels <0.1%, 99Mo breakthrough <0.030% and radiochemical purity (RCP) >98%. All the extracted 99mTcO4- batches complies sterility test, endotoxin limit (EL) <5EU/mL. The RCP of all the labeled 99mTc-RP >95%. The autosolex delivers much less radiation dose to the operator than the convention manually handled MEK based solvent extraction generator. CONCLUSIONS: Autosolex Generator was successfully used to obtain pharmaceutical grade 99mTcO4- from LSA 99MoO42- and generator is safe in radiological and pharmacological point of view. The suitability of the autosolex for use in hospital radiopharmacy was shown by using the 99mTcO4- to prepare various 99mTc-RP and using these 99mTc-RP for scintigraphic imaging in patients.

Role of fluorine-18 fluorodeoxyglucose positron emission tomography in a case of renal cell carcinoma to differentiate tumor thrombus from bland thrombus.

Tumor thrombus is a rare complication of many solid tumors. We present a case of renal cell carcinoma whose baseline contrast-enhanced computerized tomography (CT) revealed an heterogeneously enhancing mass in the upper half of right kidney with tumor thrombus in the right renal vein extending to suprarenal inferior vena cava (IVC), crossing the cavoatrial junction and reaching up to the right atrium (Grade IV). Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT imaging revealed large irregular right renal mass, hypermetabolic tumor thrombus extending from the right renal vein to suprarenal IVC reaching up to the right atrium. There was no FDG uptake noted in the infrarenal IVC and bilateral iliofemoral venous thrombi. Thus, 18F-FDG PET/CT was not only helpful in the staging, but was also helpful in differentiating tumor thrombus from bland thrombus in our patient.

Postoperative distal ureteric and bladder cuff recurrence in a Grade I renal transitional cell carcinoma diagnosed and restaged by fluorodeoxyglucose positron emission tomography-computed tomography.

A 56-year-old male having Grade I transitional cell carcinoma (TCC) of left kidney, postleft nephrectomy and upper 1/3(rd) ureterectomy presented with painless hematuria. Restaging fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) revealed abnormal linear FDG uptake in the lower 2/3(rd) of the left ureter and in the bladder adjacent to the left vesicoureteric junction, no locoregional adenopathy nor distant metastases (Figures 1 and 2- left column). Patient underwent left lower ureterectomy with partial cystectomy. Postoperative histopathology was TCC. Instillation of Bacillus Calmette-Guérin injection in the bladder was done postoperatively. A follow-up FDG PET/CT scan performed 3 months postoperatively was revealed no abnormal focal FDG uptake in the whole body revealing disease free status. FDG PET was helpful in diagnosing tumor recurrence in the distal remnant ureter. This case attempts to highlight the role of FDG PET/CT in follow-up, residual and recurrence evaluation.

Evaluation of (18)F-FDG Uptake Pattern in Brown Adipose Tissue Over Extended Time Period as Assessed by Multiple Time Point (18)F-FDG-PET.

PURPOSE: To study the (18)F-FDG uptake pattern in brown adipose tissue (BAT) over an extended time period, by multiple-time-point fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. The primary objective for this kind of research was that it could form a basis and may have further implications for obesity research, metabolic diseases and for cachexia of both malignant and benign origin. METHODS: A total of 12 patients who had undergone routine FDG-PET for disease evaluation and had demonstrated prominent BAT uptake in their baseline scans were selected. The patients with the diagnosis of neuroendocrine tumors were excluded. Maximum standardized uptake values (SUVmax) were calculated in the BAT of the supraclavicular and paravertebral areas of either side, and were analyzed separately to examine their behavior individually. Time activity curves (TACs) were generated for [A] BAT SUVmax values and [B] SUVmax ratio of BAT/lung (B/L SUVmax ratio) at various time points. RESULTS: Ten out of the 12 patients were imaged at four time points, and two patients were imaged for two time points. Amongst a total of n = 30 sites, 23 were imaged at four time points and seven were imaged at two time points. Seventeen out of 30 area sites (56.67 %) demonstrated a peak value at 60 min and a falling trend of SUVmax afterwards; the remaining showed a peak uptake value between 85 and 300 min after the first scan (i.e. 145-360 min after injection), and falling values thereafter. With regard to the B/L SUVmax ratio, ten out of 30 sites (33.33 %) demonstrated peak uptake at 60 min, and the remaining showed a rise, with peak uptake at times between 85 and 300 min after the first scan (i.e. 145-360 min after injection) and falling values thereafter. No additional area of BAT uptake was observed over the extended time period in this study. CONCLUSION: Wide variability was observed in the BAT FDG uptake over an extended period of time. Nearly half of the sites demonstrated an increase in FDG uptake until 360 min (i.e. 6 h) after injection, while the remaining half showed peak uptake at 1 h and subsequent fall of uptake. In the future, it will be worthwhile to study whether there exists any difference in time course of FDG uptake in brown fat between patients with cancer and those scanned for benign etiologies, or between obese and non-obese individuals.

Unusual case of adrenal and renal metastases from papillary carcinoma of thyroid.

We report a rare case of adrenal and renal metastases from papillary thyroid carcinoma (PTC). A 30-year-old man underwent total thyroidectomy with left neck dissection for cytology proven nodal metastases from PTC. This was followed by high-dose radioiodine therapy with a dose of 265 mCi (9.805 GBq). Thereafter, patient was lost to follow-up. He presented 2 decades later with low backache radiating to both the lower limbs. Magnetic resonance imaging examination of spine detected left SI joint, dorsal and lumbar vertebral metastases. A whole-body radioiodine scan showed extensive iodine avid foci in thyroid bed, mediastinum, bilateral lungs, liver, bones, and in bilateral lumbar regions. An abdominal single photon emission computed tomography-computed tomography (CT) revealed the lumbar lesions to be within bilateral adrenal glands. Contrast-enhanced CT of abdomen revealed lesions in bilateral adrenals and renal regions suggestive of metastases. A CT-guided biopsy of left adrenal focus confirmed metastasis from the carcinoma of thyroid. A high degree of suspicion with further radiologic and cytologic correlation clinched the diagnosis of both adrenal and renal metastases from PTC, which has been rarely reported. Fortunately, radioiodine concentration in adrenal metastases made them amenable to high-dose radioiodine therapy. Therefore, 225 mCi (8.325 GBq) of radioiodine was administered to this patient. This case is a strong reminder of the fact that regular and long-term follow-up is imperative in the management of thyroid cancer patients.

Can carbonated lime drink intake prior to myocardial perfusion imaging with Tc-99m MIBI reduce the extracardiac activity that degrades the image quality and leads to fallacies in interpretation?

BACKGROUND: During myocardial perfusion imaging with Tc-99m sestamibi, intestinal and hepatic radiotracer activity commonly interfere with visualization of the inferior wall of the myocardium leading to difficulties in interpretation. This study was undertaken to assess if carbonated lime drink ingestion prior to imaging prevents the said interference and improves the quality of images. MATERIALS AND METHODS: The study group comprised 33 consecutive patients including 26 males (age range: 30-80 years) and 7 females (42-62 years) who were referred for myocardial perfusion imaging. Of 33 patients, 21 (18 males, 3 females) were imaged at rest, 5 patients (3 males, 2 females) underwent physical stress, and 7 patients (5 males, 2 females) had pharmacological stress with adenosine. Five to 10 minutes after intravenous injection of 296 to 444 MBq (8-12 mCi) Tc-99m MIBI, anterior, and left anterior oblique (LAO) 45 degree planar views were acquired with a gamma camera using LEHR collimator. Each view was acquired for 100 seconds in a 256 x 256 matrix in all patients. Thereafter each patient was administered about 250 mL of a carbonated lime drink and repeat views were acquired within 5 minutes with the same parameters. Quantitative assessment of counts in the inferior wall of myocardium (M) to those in adjacent abdomen (A) was performed on both pre- and postintervention studies by drawing an ROI of about 50 +/- 5 pixels. M/A ratios were recorded for each patient in both the groups. The student t test was performed to evaluate the significance of difference between pre- and postintervention images. P < 0.05 was considered significant. All patients underwent myocardial perfusion single photon emission computed tomography. RESULTS: It was found that the inferior wall of the myocardium was better visualized, and there was no interference from gut or hepatic tracer activity in postintervention planar and single photon emission computed tomography reconstructed views as compared with preintervention images in all patients. The M/A ratio expressed as mean +/- SD was significantly higher in the postintervention group, viz. 2.19 +/- 0.71 in the anterior and 2.07 +/- 0.70 in the LAO45 views as compared with those of preintervention values of 1.50 +/- 0.59 in the anterior and 1.41 +/- 0.49 in the LAO 45 views, respectively (P < 0.001). CONCLUSION: We conclude that intake of carbonated lime drink is a simple and an effective technique to improve the image quality of the inferior wall of the myocardium on myocardial perfusion imaging with Tc-99m MIBI. This technique may also help in reducing the time interval between injection of radiotracer and imaging, which is otherwise delayed in routine practice.