Noninvasive treatment of keloid using customized Re-188 skin patch.

Keloids are developed as fibrotic scar at the site of surgery or trauma and often enlarge beyond the original scar margins. Re-188 colloid coated customized patch was superficially fixed onto the lesion for 3 hrs. The same patch was reapplied on the lesion on third day for 3 hrs. The patients were followed up at 1, 3,6 and 12 months post treatment. The size and elevation of the keloid lesion was reduced after treatment. The total radiation dose from the patch (day-1 and day-3) was 100 Gy/mCi of Re-188. The radioactive patch treatment of keloids is noninvasive, painless and safe with prolonged outcome.

Increased advanced glycation end product specific fluorescence in repeatedly heated used cooking oil.

Repeated heating of cooking oils is known to cause their degradation and generation of toxins. Dietary Advanced glycation end products (dAGEs) are formed when the foods are cooked in dry heat at very high temperatures. dAGEs are believed to contribute significantly to total pool of AGEs in body. In this study, cooking oil samples used for frying snacks were collected from 102 shops. AGEs were extracted using Aqueous-TCA-chloroform method. Fluorescent AGE levels were determined using a fluorescence spectrophotometer and compared with AGEs in corresponding fresh oil samples collected from same shops. Palm oil was most commonly (62.5%) used for cooking. Most of the samples were subjected to several rounds of heating (1-6). AGE specific fluorescence (ASF) in used oil (range = 8.5-745.11) samples was found to be significantly higher in 88/102 as compared to the corresponding fresh oil samples. Treatment with inhibitors like lime concentrate and vitamin C decreased ASF (10/14 and 10/11 samples respectively) of the used oils. The results suggest that cooking oil subjected to repeated heating can contribute to increase in fluorescent AGEs in diet. Simple practices like liberal use of common household substances like lime concentrate may help to reduce these in fried food.

Comparison of 99m Tc-methylenediphosphonate and 68 Ga-BPAMD PET/computed tomography imaging in bone metastasis.

OBJECTIVE: Bone is considered as the third most common site of metastases, besides lung and liver. Early detection of skeletal metastases aids in better management of skeletal-related events. In the present study cold kit-based 2,2 ' ,2 '' -(10-(2-((diphosphonomethyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (BPAMD) was labeled with 68 Ga. The radiolabeling parameters and clinical evaluation in patients with suspected bone metastases were compared with routinely used 99m Tc-methylenediphosphonate ( 99m Tc-MDP). METHODOLOGY: The kit components of MDP were incubated with at room temperature for 10 min, followed by radiochemical purity testing using thin-layer chromatography. For radiolabeling of BPAMD, the cold kit components reconstituted in 400 µL of HPLC grade water were transferred and incubated with 68 GaCl 3 in the reactor vessel of the fluidic module at 95°C for 20 min. Radiochemical yield and purity were determined with instant thin-layer chromatography using 0.5 M sodium citrate as mobile phase. For clinical evaluation, patients ( n = 10) with suspected bone metastases were enrolled. 99m Tc-MDP and 68 Ga-BPAMD scans were performed on two different days in random order. Imaging outcomes were noted and compared. RESULTS: Radiolabeling of both tracers is facile using cold kit, although BPAMD requires heating. The radiochemical purity was observed to be greater than 99% for all preparations. Both MDP and BPAMD detected skeletal lesions; however, additional lesions were detected in total of seven patients which were not visualized clearly on 99m Tc-MDP scan. CONCLUSION: BPAMD can be easily tagged with 68 Ga using cold kits. The radiotracer is suitable and efficient for detection of bone metastases using PET/computed tomography.

Theragnostic Radionuclide Pairs for Prostate Cancer Management: 64Cu/67Cu, Can Be a Budding Hot Duo.

Prostate cancer (PCa) is one of the preeminent causes of mortality in men worldwide. Theragnostic, a combination of therapy and diagnostic, using radionuclide pairs to diagnose and treat disease, has been shown to be a promising approach for combating PCa. In PCa patients, bone is one of the most common sites of metastases, and about 90% of patients develop bone metastases. This review focuses on (i) clinically translated theragnostic radionuclide pairs for the management of PCa, (ii) radionuclide therapy of bone metastases in PCa, and (iii) a special emphasis on emerging theragnostic radionuclide pair, Copper-64/Copper-67 (64Cu/67Cu) for managing the disease.

Nuclear medicine in the management of superficial skin abnormalities and institutional experience.

Keloid, hypertrophic scars and basal cell carcinoma (BCC) falls under the category of non-melanoma skin cancer. Intralesional steroids, external beam radiation therapy, 5-Fluorouracil, cryotherapy, laser, etc are the available treatment options. However, recurrence has been reported with each type of treatment mode. In the present article, various treatment modes have been discussed and institutional experience of Rhenium-188 skin patches for the treatment of keloids and BCC has been discussed.

Cold kit for Rhenium-188 microspheres based selective intra-arterial therapy (SIRT): Preparation, characterization and feasibility study.

Selective-intra-arterial radionuclide therapy (SIRT) using radiolabeled microspheres are being widely employed for the delivery of therapeutic radioisotope to liver cancers by exploiting the dual blood supply to liver. It delivers the therapeutic radiations to tumor and spares the healthy liver. Several radiolabeled microspheres formulations, labelled with 90Y, are commercially available. However, high-cost leads to unaffordability for several patients. 188Re-based therapy seems affordable due to commercial availability of 188W/188Re generator that have long shelf-life of more than 6 months. To provide affordable solution, the microsphere cold kit with quick and facile methodology for 188Re radiolabeling has been developed. The microsphere cold kit has been characterized for their physicochemical properties. The Quality Control (QC) tests were also performed for clinical application. The feasibility studies were performed to study distribution and retention of 188Re microspheres in tumor. The results demonstrated that the developed cold kit enables facile and quick radiolabeling with 188Re. 188Re microspheres showed good retention in tumor and found suitable for SIRT.

Tc-99m-tamoxifen: A novel diagnostic imaging agent for estrogen receptor-expressing breast cancer patients.

PURPOSE The aim of the study was to radiolabel, characterize, and perform in vitro and in vivo assessment of Technetium-99m (Tc-99m) tamoxifen for screening ER expressing lesions in breast cancer patients. METHODS In this study, tamoxifen has been radiolabeled with Tc-99m via Tc-99m-tricarbonyl core. The characterization and quality control tests of Tc-99m-tamoxifen were performed. In vitro recep- tor binding and blocking studies were performed in both positive control (MCF-7) and negative control cell lines (MDA-MB-231). Normal biodistribution studies were performed in female Wistar albino rats. The pilot clinical studies were performed in 4 ER-expressing breast cancer patients. Of the 4 patients, 1 was on tamoxifen therapy. All 4 patients had also undergone Fluorine-18 fluorodeoxyglucose (F-18-FDG) positron emission tomography/computed tomography. RESULTS Tamoxifen was radiolabeled with Tc-99m via Tc-99m-tricarbonyl core with more than 95% radio- chemical yield. Mass spectra showed a peak corresponding to the molecular weight of Tc-99m- tricarbonyl and Tc-99m-tamoxifen. The site of binding of Tc-99m-tricarbonyl with tamoxifen was determined by proton nuclear magnetic resonance. The Tc-99m-tamoxifen showed 30% binding with MCF-7 and only 1%-2% receptor binding with MDA-MB-231 cell lines. Also, the percentage of receptor binding was drastically reduced (up to 72%) when ER was saturated with 50 times the excess molar ratio of unlabeled tamoxifen. In a pilot patient study, Tc-99m-tamoxifen uptake was observed in primary and metastatic lesions. However, no uptake was observed in a patient who was on tamoxifen therapy. The uptake of F-18-FDG was noted in all the patients. CONCLUSION Tamoxifen was radiolabeled with an in-house-synthesized Tc-99m-tricarbonyl core. The radio- labeled complex has been characterized and evaluated for receptor specificity in in vitro and in vivo studies. Also, this is the first clinical study using Tc-99m-tamoxifen for imaging ER. More patients need to be evaluated to further explore the role of Tc-99m-tamoxifen in ER-expressing lesions.

Re-188-tricarbonyl tamoxifen as a theranostic radiopharmaceutical for estrogen receptor expressing breast cancers: radiolabeling, characterization and in-vitro cytotoxic assessment.

PURPOSE: Development of a novel theranostic radiopharmaceutical for estrogen receptor, expressing unresectable primary and metastatic breast cancers. METHODS: Tamoxifen was radiolabeled with Rhenium-188 (Re-188) through tricarbonyl core. Radiolabeled complex was characterized by 1proton nuclear magnetic resonance spectroscopy and Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF). Various quality control tests such as sterility, apyrogenicity, and radiochemical purity (RCP) were performed to assess the suitability of the radiopharmaceutical for intravenous administration. In-vitro cell culture studies were performed for cytotoxic assessment. In addition to this, exposure due to different doses of Re-188-tricarbonyl tamoxifen was also calculated. RESULTS: Re-188-tricarbonyl and Re-188-tricarbonyl tamoxifen showed more than 99% RCP. Sample was found to be sterile and pyrogens levels were within the permissible limit. Re-188-tricarbonyl tamoxifen was successfully characterized by MALDI-TOF and 1H-NMR spectroscopy. Re-188 (1.480 MBq) and tamoxifen (0.027 or 0.054 µM) individually showed 36 and 70% cell death, respectively. However, radiolabeled complex (Re-188-tricarbonyl tamoxifen) with the same amount of radioactivity (1.480 MBq) increased the cell death to more than 90% with one-fifth to one-tenth molar concentration of tamoxifen (0.0054 µM). CONCLUSION: Re-188-tricarbonyl tamoxifen can be synthesized in-house in radiopharmacy lab. Radionuclide therapy with Re-188-tricarbonyl tamoxifen can be given using 10 times less amount of tamoxifen as compared to cold tamoxifen.

Development of 68Ga DOTA-CRH for PET/CT Imaging of ACTH-Dependent Cushing's Disease: Initial Study.

Purpose: Adrenocorticotropic hormone (ACTH)-dependent Cushing's disease accounts for 75% cases of the endogenous Cushing's syndrome. The size of lesion is usually very small, which results in false-negative magnetic resonance imaging (MRI) even after biochemical confirmation of the disease. Corticotrophin-releasing hormone (CRH) the key controller of hypothalamus-pituitary--adrenal axis binds to CRH receptor R1 and R2. CRH R1 is overexpressed in pituitary adenomas. The present study aims to target these overexpressed receptors with 68Ga-DOTA-CRH for noninvasive imaging of ACTH-dependent pituitary adenomas. Materials and Methods: Custom-synthesized 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-CRH peptide was purified by high performance liquid chromatography (HPLC) and characterized by mass spectra. Postradiolabeling optimization with 68Ga, quality control tests were carried out to ensure the suitability of 68Ga DOTA-CRH for intravenous administration. A pilot study consisting of 15 patients including 6 known cases of macroadenoma underwent 68Ga-DOTA-CRH regional brain positron emission tomography/computed tomography (PET/CT). The optimal imaging time and biodistribution studies were performed in five patients' whole-body and serial brain PET/CT imaging. Lesion activity was determined as SUVmax and correlated with CE-MRI and histopathology of excised tissue. Results: A retention time of 11.3 min and mass of 5145 Da was observed on HPLC and mass spectra. Radiolabeling yield of >98% was achieved under optimized conditions using 25-100 µg of conjugated peptide for 10-22 mCi of 68Ga. The quality control results were in agreement with acceptable criteria. 68Ga-DOTA-CRH was able to delineate ACTH secreting corticotropinoma in all 15 patients. Physiological uptake of radiotracer was observed in liver and spleen with diffused marrow activity. Excretion was noted by renal route. Imaging results were in correlation with CE-MRI and histopathology of excised tissue. Conclusion: 68Ga-DOTA-CRH PET/CT is a promising molecular imaging modality for detection of ACTH-dependent microadenoma.

99mTc Tamoxifen for Imaging Estrogen Receptor Expression in Metastatic Breast Cancer Patient.

Estrogen receptor-expressing breast cancer exhibits better prognosis due to responsiveness to antiestrogen treatment. Therefore, knowledge of the estrogen receptor status of a tumor is an important prognostic and predictive indicator in breast cancer. We present noninvasive imaging of estrogen receptors with Tc tamoxifen that can identify the active tumor and approachable sites for biopsy. It may help in selection of patients for hormone replacement therapy and in assessment of receptor status in recurrent disease and also in response evaluation.

Role of [68Ga]DOTANOC PET/computed tomography and [131I]MIBG scintigraphy in the management of patients with pheochromocytoma and paraganglioma: a prospective study.

PURPOSE: The primary aim of study was to compare role of iodine-131 (I-131)-labeled metaiodobenzylguanidine ([I]MIBG) and gallium-68 (Ga-68)-labeled DOTA-l-Nal3-octreotide ([Ga]DOTANOC) PET/computed tomography (CT) in patients with pheochromocytoma (PCC) and paraganglioma (PGL), subsequent follow-up to see management. The secondary aim was to see association of germline mutation in histopathologically proven patients. PROCEDURES: We performed [Ga]DOTANOC PET/CT and [I]MIBG in 106 patients (61 men; age: 38.5 ± 16.2 years) of known or suspected PCC/PGL. Following scans, 16 histopathologically proven patients were screened for germline mutations. RESULTS: [I]MIBG detected 41 lesions in 34 patients and [Ga]DOTANOC PET/CT detected more than 79 lesions in 55 patients. The mean duration of follow-up was 20.6 ± 16.5 months. Management following scans: surgery in 35 patients (positive histopathology in 34 patients, negative in 1 patient); lutecium-177 (Lu-177)-labeled DOTA-0-Tyr-3 octreotate ([Lu]DOTATATE) therapy in 2 patients; chemotherapy in 1 patient; conservative therapy in 34 patients; no therapy in 17 patients; 2 patients have died and 3 were lost to follow-up. Among 12 previously operated, 2 patients showed metastatic disease and 1 showed residual disease. Out of 16 patients who underwent genotypic analysis (15 operated), 8 were positive for germline mutations. Mutations were seen in SDHB, RET, VHL, MDH2 and SDHA genes, including two germline mutations in two patients. Deletion was observed in one patient in SDHB gene and substitution in all other mutations. Four novel mutations in MDH2 (c.1005G>C, c.916G>A, c.580G>A) and SDHB (c.378_380delAAT) were observed (SRA accession: PRJNA551457). CONCLUSIONS: [Ga]DOTANOC PET/CT should be considered as a first-line investigation in PCC/PGL especially at high risk of metastasis and screening of persons with familial syndrome.

Freeze-dried microspheres for selective intra-arterial radionuclide therapy: an affordable solution.

OBJECTIVE: Selective intra-arterial radionuclide therapy (SIRT) using radiolabelled microspheres is for the delivery of therapeutic radioisotope to liver cancers and thus, sparing healthy liver. Several radiolabelled microspheres are commercially available. The main issue associated with these microspheres is affordability. Re-188 is a generator produced radionuclide, emits high energy therapeutic beta particle and imageable gamma photons for pre- and post-therapy dosimetry. METHODS: Tc-99m/Re-188 labelled microspheres have been developed and quality control tests have been performed for suitable clinical use. The clinical studies with Re-188 microspheres for SIRT have been performed. Post-therapy images were acquired for dosimetry. RESULTS: The microspheres were found to possess spherical morphology of less than 20 µm size. The quality control revealed the suitability of microspheres for intravenous administration. The preliminary studies in thirty patients demonstrated good retention in tumor and high tumor to normal liver ratio. Re-188 microspheres were well tolerated by patients. Same microspheres labelled with either Tc-99m or Re-188 were used for pretherapy dosimetry and Re-188 labeled microspheres for therapy (SIRT) as a single-day procedure. CONCLUSION: The freeze-dried microspheres may emerge as highly cost-effective candidates for both pre-therapy dosimetry and SIRT and may benefit a large population with inoperable liver cancer.

Two Cases of 188Re Microspheres for Inoperable Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. Often, patients present with inoperable and advanced disease. Selective internal radionuclide therapy offers prolonged survival and improved quality of life by delivering high radiation dose to the tumor with minimal complications. We report 2 inoperable cases of HCC treated with therapeutic dose of indigenously developed Re microspheres delivered to the hepatic lesions by transarterial catheterization. Follow-up CT revealed necrosis within the lesion, suggesting response to selective internal radionuclide therapy. Re microspheres may be a potential treatment option for inoperable HCC with or without portal vein thrombosis.

Concentration protocol of rhenium-188 perrhenate eluted from tungsten-188/rhenium-188 generator for the preparation of high-yield rhenium-188-labelled radiopharmaceuticals.

Rhenium-188 (Re) is a ß, γ emitter and considered a theranostic radionuclide. It is used for bone pain palliation, treatment of unresectable hepatocellular carcinoma, skin keloids, etc. Re perrhenate is eluted from a W/Re generator in large volumes (8-14 ml) of 0.9% normal saline. Concentrating Re to 1-2 ml volume is important for high radiolabelling yield of various Re radiopharmaceuticals, especially when the generator is old. For this, ion exchange column was prepared in-house, and Re was concentrated using silver ion exchange column and QMA cartridge. Re perrhenate eluted in saline was concentrated to 1 ml with more than 99% yield.