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.

Analysis of image quality by regulating beta function of BSREM reconstruction algorithm and comparison with conventional reconstructions in carcinoma breast studies of PET CT with BGO detector.

BACKGROUND: The study aimed to evaluate the beta penalization factor of the BSREM reconstruction algorithm on a five-ring BGO-based PET CT system and compared it with conventional reconstructions. METHODS: Retrospective study involves 30 breast cancer patient data of 18F-fluorodeoxyglucose ( 18 F-FDG) PET CT for reconstruction with OSEM, OSEM + PSF, and BSREM under variable ß factors ranging from 200 to 600 in the steps of 50. Liver noise, lesion SUVmax, SBR, and SNR for each reconstruction were calculated. Quantitative parameters of each beta factor of BSREM were compared with OSEM and OSEM + PSF, using the Wilcoxon sign rank test with Bonferroni correction, a value of P < 0.002 was considered statistically significant. Visual scoring by two readers was also evaluated. RESULTS: Thirty lesions of mean size 1.91 ± 0.58 cm range (0.7-3.6 cm) were identified. Liver noise and SBR were reduced, whereas SNR was increased with an increasing ß value of BSREM. In comparison with OSEM, liver noise was not significantly different from ß200 and ß250. SNR of OSEM was significantly lower than any other ß factors and SBR of ß factor less than 500 was significantly higher than OSEM. In comparison with OSEM + PSF, liver noise was not significantly different from ß400 and ß350-500 do not show a significant difference in SNR and SBR compared with OSEM + PSF. ß350 scored highest under visual scoring with a moderate agreement. CONCLUSION: The study quantitatively indicates the optimum beta range of ß250-450 and the qualitative evaluation indicates that ß350 is an optimum beta factor of BSREM in breast cancer cases for 18 F-FDG WB-PET CT.

Evaluation of Tetrofosmin Cold Kit Fractionation Using Alternative New Method of Quality Control for Testing Radiochemical Purity.

Objective The aim of this study is to establish a method for the fractionation of tetrofosmin cold kit under different storage conditions and to optimize an alternate chromatography method from the reference method to test radiochemical purity (RCP). Materials and Methods Tetrofosmin cold kit vial was fractionated aseptically in six equal fractions and stored in vials and syringes. To test the stability of the reconstituted solution for a longer duration, the mother vials and syringes were stored at two different temperatures, that is, at 4°C and at -20°C till further used. Radiolabeling of fractionated tetrofosmin was performed as per the standard labeling protocol. Radionuclide purity, radioassay, and pH were tested. Radiolabeling efficiency and RCP were determined by paper chromatography. Results Radionuclide purity of eluate was greater than 99.9%. The pH of technetium-99m (Tc-99m) eluate and Tc-99m tetrofosmin was between 4.5-7.5 and 7.5-9.5, respectively. The deviation in the radioactivity during all measurements was less than 1%. The kits fractioned in glass vials resulted in higher radiolabeling yield and RCP as compared with kits fractionated in syringes. The RCP of glass vial versus syringe was observed to be greater than 95 versus 90% and 95 versus 80% at -20°C and 4°C, respectively. Conclusion Tetrofosmin kit can be used in a cost-effective manner by fractionation. One tetrofosmin vial can be used in six fractions for up to 15 days when stored at -20°C and 4°C freezer temperature. The alternative method to check the RCP of Tc-99m tetrofosmin is safer and less time consuming as compared with the reference method.

Challenges and opportunities in developing Actinium-225 radiopharmaceuticals.

Actinium-225 (225Ac) has emerged as a promising therapeutic radioisotope for targeted alpha therapy. It emits net four alpha particles during its decay to stable daughter bismuth-209, rightly called an in-vivo nano-generator. Compared to the worldwide demand of 225Ac, the amount produced via depleted thorium-229 sources is minimal, making it an expensive radionuclide. However, many research groups are working on optimizing the parameters for the production of 225Ac via different routes, including cyclotrons, reactors and high-energy linear accelerators. The present review article focuses on the various aspects associated with the development of 225Ac radiopharmaceuticals. It includes the challenges and opportunities associated with the production methods, labeling chemistry, in-vivo kinetics and dosimetry of 225Ac radiopharmaceuticals. A brief description is also given about the 225Ac radiopharmaceuticals at preclinical stages, clinical trials and used routinely.

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.

Angiogenesis versus Metabolic Imaging in Locally Advanced Breast Cancer Patients - A Comparative Study.

Purpose: The comparison of angiogenesis imaging (Ga-68-DOTA-Arginine-Glycine-Aspartic Acid [RGD]) positron emission tomography/computed tomography [PET/CT]) with metabolic imaging (F-18 fluorodeoxyglucose [FDG] PET/CT) in primary staging and response assessment to neoadjuvant chemotherapy (NACT) in locally advanced breast cancer (LABC) patients. Methods: In this prospective study, 85 female patients with LABC were subjected to two PET/CT studies (Ga-68-DOTA-RGD2 and F-18 FDG) within 1 week of each other. Thirty patients had repeat studies 4 weeks after completing eight cycles of NACT. Response assessment was done by RECIST 1.1 criteria. Results: Ga-68-DOTA-RGD2 and F-18 FDG uptake in the primary tumor were seen in all patients. Ipsilateral axillary and internal mammary lymph nodes were detected in 77 (90.5%) versus 80 (94.1%) and 22 (25.8%) versus 27 (31.7%) patients on Ga-68-DOTA-RGD2 and F-18 FDG scans, respectively. Ipsilateral supra-clavicular lymph nodes and skeletal lesions were noted in 17 (20%) versus 21 (24.7%) patients and 23 (27.0%) versus 24 (28.2%) patients on Ga-68-DOTA-RGD2 versus F-18 FDG studies, respectively. However, the Ga-68-DOTA-RGD2 did not show uptake in F-18 FDG avid liver lesions (LLs) in 10 patients, adrenal lesion in one patient, mediastinal lymph nodes in 2 patients, lung nodules, and pleural soft-tissue deposits, each in one patient. In response assessment, 23 and 25 patients had concordance with RECIST1.1 criteria on F-18 FDG and Ga-68-DOTA-RGD2 scans, respectively. However, there were discordant results in four patients on Ga-68-DOTA-RGD2 scan and two patients on F-18 FDG scans. Conclusion: Metabolic imaging is better in primary staging and chemotherapy response assessment than angiogenesis imaging in LABC patients. The latter may miss the metastatic soft-tissue deposits, adrenal, and LLs.

Humanoid Training Phantom for Positron Emission Tomography-Computed Tomography-Guided Percutaneous Biopsy.

Positron emission tomography-computed tomography (PET-CT)-guided biopsy is being increasing practiced worldwide with indications in sampling of lung, abdominal, bone lesions, and among others. Training for PET-guided Interventions at select centers is carried out under supervision of an expert on real patients, similar to training for interventional radiology procedures. Simulation center training has been shown to be useful in improving efficiency of resident trainees. We report the development of concept, design, and practical application of a simplified humanoid training phantom for PET-guided interventions.

F-18 fluorocholine positron emission tomography- computed tomography in initial staging and recurrence evaluation of prostate carcinoma: A prospective comparative study with diffusion-weighted magnetic resonance imaging and whole-body skeletal scintigraphy.

Prostate cancer (PCa) is one of the major causes of death due to cancer in men. Conventional imaging modalities such as magnetic resonance imaging (MRI) provide locoregional status, but fall short in identifying distant metastasis. C-11 choline F-18 fluorocholine (F-18 FCH) has been shown to be useful in imaging of PCa. The present prospective study evaluates and compares the role of F-18 FCH positron emission tomography-computed tomography (PET-CT) with locoregional MRI and whole-body bone scintigraphy in PCa patients for initial staging and recurrence evaluation. This study included a total of 50 patients. Tc-99m skeletal scintigraphy, F-18 FCH PET-CT, and diffusion-weighted MRI of the pelvic region were performed within a span of 2-3 weeks of each other, in random order. For the primary site, core biopsy findings of the lesion were considered as gold standard. The kappa test was used to measure agreement between bone scintigraphy, F-18 FCH, and MRI. For comparing Tc-99m bone scintigraphy, F-18 FCH, and MRI, McNemar's test was applied. F-18 FCH PET-CT and MRI were able to detect primary lesion in all initial staging patients. The sensitivity and specificity of F-18 FCH PET-CT versus MRI were found to be 92.8% versus 89.2% and 100 versus 80%, respectively, for the recurrence at the primary site. A total of 55 bony lesions at distant sites were detected on F-18 FCH PET-CT in comparison to 43 bone lesions on whole-body bone scintigraphy. F-18 FCH PET/CT also detected additional lung lesions in 2 patients and abdominal lymph nodes in 12 patients. F-18 FCH PET-CT could detect primary lesions, local metastasis, bone metastasis, and distant metastasis in a single study and is also a useful modality in recurrence evaluation in PCa patients.

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.

Efficacy and safety of 177Lu-DOTMP in palliative treatment of symptomatic skeletal metastases: a prospective study.

AIMS: Bone-seeking radiopharmaceutical 177Lu-DOTMP with favorable pharmacokinetics in the preclinical studies has been evaluated for its role in reducing bone pain and improving quality of life (QOL) in patients with symptomatic skeletal metastases. METHOD: Patients with painful widespread skeletal metastases documented on 99mTc-MDP bone scintigraphy were intravenously administered 37 MBq/kg of 177Lu-DOTMP. Visual analogue score (VAS), analgesic score, European Cooperative Group of Oncology (ECOG) and the European Organization of Research and Treatment of Cancer QLQ-C30 of all the patients were assessed at baseline and posttherapy follow-up. Adverse effects were graded according to NCI-CTCAE V 5.0. RESULTS: Twenty-seven patients with painful widespread skeletal metastases (men 18; median age 61 years; range: 18-81) were studied for their responses as complete response, partial response, minimal response, no response and pain progression based on VAS and analgesic score. Overall response was seen in 77.8% of patients (complete, partial and minimal in 29.6, 33.3 and 14.8%, respectively) with significant improvement in median VAS and mean analgesic score at 2 months posttherapy from baseline (P < 0.001). The best response was seen in patients with breast cancer (100%) followed by prostate cancer (81%) and lung cancer (28%). Improvement in QOL was noted in 40% of patients, with change in ECOG score from 3.07 ± 0.67 at baseline to 2.6 ± 0.9 at 2 months posttherapy. Grade 2/3 anemia, grade 1/2 leukopenia and grade 1/3 thrombocytopenia were seen in 37, 11.1 and 18.5% patients respectively in the follow-up. CONCLUSION: 177Lu-DOTMP appears to be efficacious treatment for bone pain palliation with improvement in QOL though less effective in patients with lung cancer. The patients had transient mild-moderate hematotoxicity.

Prospective Comparison of Angiogenesis-Specific 68Ga-RGD2 PET/CT Imaging Parameters and DAS28-ESR in Rheumatoid Arthritis.

OBJECTIVE: The aim of this study was to compare the performance of angiogenesis-specific 68Ga-RGD2 PET/CT with Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) in assessing disease activity and treatment response in rheumatoid arthritis (RA). METHODS: This was a prospective study comparing the performance of 68Ga-RGD2 PET/CT and DAS28-ESR in 30 RA patients. All of them underwent 68Ga-RGD2 PET/CT scan from head to toe and clinical examination at the baseline. A repeat scan and clinical examination were done in 27 patients after 3 months of treatment with disease-modifying antirheumatic drugs ± steroids. Three PET parameters, that is, PJC (PET-positive joint count), aSUVmax (average SUVmax), and hSUVmax (highest SUVmax), of positive joints were compared with the DAS28-ESR for disease activity assessment and response evaluation. RESULTS: Among the 3 PET parameters, PJC showed a significant correlation with the DAS28-ESR (0.64, P < 0.01). A significant change was observed with treatment in the DAS28-ESR and PET parameters of 27 patients at follow-up. There was significant correlation between percentage changes in DAS28-ESR and scan parameters such as PJC (0.689, P < 0.001), aSUVmax (0.712, P < 0.001), and hSUVmax (0.555, P = 0.003) values. The absolute change in aSUVmax value could accurately discriminate (area under the curve, 0.98; P = 0.001) European League Against Rheumatism responders from nonresponders. CONCLUSIONS: 68Ga-RGD2 PET/CT is a promising tool for objective assessment of disease activity and treatment response in patients with RA.

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.

Molecular Imaging Targeting Corticotropin-releasing Hormone Receptor for Corticotropinoma: A Changing Paradigm.

BACKGROUND: Corticotrophin-releasing hormone (CRH) is the major regulator of adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary and acts via CRH-1 receptors (CRH-1R). Corticotropinoma though autonomous, still retain their responsiveness to CRH and hence, we hypothesize that in vivo detection of CRH-1 receptors on pituitary adenoma using Gallium-68 (68Ga)-tagged CRH can indicate the functionality of adenoma, and combining it with positron emission tomography-computed tomography (PET-CT) can provide requisite anatomical information. METHODS: Subjects with ACTH-dependent Cushing's syndrome (CS) (n = 27, 24 with Cushing's disease [CD], 3 with ectopic CS [ECS]) underwent 68Ga CRH PET-CT. Two nuclear medicine physicians read these images for adenoma delineation and superimposed them on magnetic resonance imaging (MRI) sella. The information provided was used for intraoperative navigation and compared with operative and histopathological findings. FINDINGS: 68Ga CRH PET-CT correctly delineated corticotropinoma in all the 24 cases of CD, including the 10 cases with adenoma size < 6mm (4 cases were negative on MRI). Corticotropinoma location on 68Ga CRH PET fusion images with MRI were concordant with operative findings and were further confirmed on histopathology. There was no tracer uptake in the pituitary in 2 patients with ECS, while, in another, the diffuse uptake in pituitary suggested ectopic CRH production. CONCLUSION: 68Ga CRH PET-CT represents a novel, noninvasive molecular imaging, targeting CRH receptors that not only delineate corticotropinoma and provides the surgeon with valuable information for intraoperative tumor navigation, but also helps in differentiating a pituitary from an extra-pituitary source of ACTH-dependent CS. FUNDING: None.

Comparative Performance of 99mTc-TRODAT-1 SPECT/CT and 18F-FDOPA PET/CT Imaging in Patients With Parkinson's Disease, Parkinson-Plus Syndrome, and Essential Tremor.

PURPOSE: The aim of this study was to assess the utility of presynaptic dopaminergic imaging using 99mTc-TRODAT-1 SPECT/CT and 18F-FDOPA PET/CT and compare their performance in Parkinson's disease (PD), Parkinson-plus syndrome (PPS), and essential tremor (ET). PATIENTS AND METHODS: A total of 103 patients (PD = 48, PPS = 19, and ET = 36) were enrolled prospectively. Hoehn and Yahr (H&Y) staging and MDS-UPDRS (Movement Disorder Society-Sponsored Revision of Unified Parkinson's Disease Rating Scale) were done for PD and PPS cases. All the patients underwent 99mTc-TRODAT-1 SPECT/CT and 18F-FDOPA PET/CT brain scan. The scans were analyzed visually and semiquantitatively. Average pixel count and SUVmean of the striatum were calculated in SPECT and PET images, respectively, to calculate the specific uptake ratio of striatum (SUR). Comparison of scan findings and SURs among different groups and correlation with clinical characteristics was done. RESULTS: Symmetrical comma-shaped uptake was seen in bilateral striatum in ET cases with mean SURs significantly higher than in cases of early PD (H&Y stage I and II, n = 37), PD and PPS both on SPECT and PET images (P ≤ 0.001). The mean SURs between PD and PPS showed no significant difference (SPECT, P = 0.17; PET, P = 0.61). Substantial agreement (weighted κ = 0.659) was found between 99mTc-TRODAT-1 and 18F-FDOPA for the detection of presynaptic dopaminergic dysfunction. Specific uptake ratio of striatum correlation between SPECT and PET was statistically significant (r = 0.67; P < 0.01). A negative but nonsignificant correlation was found between the SURs and H&Y staging/MDS-UPDRS. CONCLUSIONS: Both 99mTc-TRODAT-1 SPECT/CT and 18F-FDOPA PET/CT showed substantial agreement and proved to be potential imaging biomarker for the detection of dopaminergic dysfunction, thus assisting in differentiating early PD/PD and PPS from ET cases.

Correction of Positron Emission Tomography Maximum Intensity Projection Image Artifact Using Retro Reconstruction Method.

Artifacts in positron emission tomography (PET)/computed tomography imaging can result from a number of factors. Presence of imaging artifacts affects interpretation and can sometimes render the image uninterpretable. Correction of artifacts can be attempted by reprocessing of data. In the present study, one PET maximum intensity projection image artifact was corrected by employing the method of retro-reconstruction.

Clinical evaluation of kit based Tc-99m-HYNIC-RGD2 for imaging angiogenesis in breast carcinoma patients.

BACKGROUND: Radiolabeled RGD peptide can be used for noninvasive in vivo imaging of αvß3 integrin receptors leading to early detection of tumor cells and hence improving the clinical outcomes. In the present study single vial kit based HYNIC RGD2 was radiolabeled with Tc-99m and evaluated in patients with breast carcinoma. METHODS: Radiolabeling was performed via bifunctional chelator method. Tc-99m 1110-2960 MBq (30-80 mCi) was added to the HYNIC-RGD2 vial. The reaction mixture was heated for 20 minutes at 100°C. After performing the quality checks, whole-body planar imaging was performed in 20 patients at 2-2.5 h post i.v. injection of 555-740 MBq (15-20 mCi) of the radiotracer. RESULTS: Radiolabeling yield of ≥98% was observed in all the formulations. Quality control tests indicated the suitability of radiopharmaceutical for intravenous administration. Physiological uptake of Tc-99m HYNIC-RGD2 was observed in the nasopharynx, salivary glands, liver, spleen, and intestine. Good uptake of radiotracer was observed in breast lesions of 18 patients. Two patients were observed to be negative. Increased uptake was also seen in metastatic sites in two patients and in lymph nodes in three patients. Scintigraphy findings were in corroboration with pathological observations. CONCLUSION: The single vial cold kit based radiolabeling of Tc-99m HYNIC-RGD2 is facile leading to its easy availability. Tc-99m HYNIC-RGD2 is a promising radiopharmaceutical which can be used for the molecular imaging of angiogenesis in breast carcinoma patients.

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.

225Ac-PSMA-617 Radioligand Posttherapy Imaging in Metastatic Castrate-Resistant Prostate Cancer Patient Using 3 Photopeaks.

PSMA-based radioligand therapies have shown the beneficial effect in metastatic castrate-resistant prostate cancer (mCRPC) patients when they become refectory to the established treatments with associated potential toxicities and high mortality rate. Ac-PSMA therapy is known to be remarkably effective in substantially pretreated mCRPC patients. However, posttherapy imaging is usually not performed as alpha emitters are really difficult to image. We presents a patient of mCRPC treated with Ac-PSMA-617, and his posttherapy whole-body scans acquired by using 3 different photopeaks (78, 218, and 440 keV) fairly demonstrated the tracer's distribution and the efficacy of targeted alpha therapy.

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.