Madan Parmar

Development of Lu-177-trastuzumab for radioimmunotherapy of HER2 expressing breast cancer and its feasibility assessment in breast cancer patients

HER2/neu is over expressed in 20–25% of breast cancers. HER2 breast cancers are aggressive and are associated with poor prognosis. The aim of this study was to develop the clinical grade Lu‐177‐trastuzumab and its preliminary evaluation for specific tumor targeting in HER2 positive breast cancer patients. Trastuzumab was conjugated to bifunctional chelator, DOTA, and characterized for integrity and the number of molecules conjugated. Radiolabeling of DOTA‐conjugated trastuzumab was optimized using Lu‐177. Quality control parameters including radiochemical purity, stability, sterility, pyrogenicity and immunoreactivity were assessed. A preliminary pilot study was conducted on breast cancer patients (n = 6 HER2 positive and n = 4 HER2 negative) to evaluate the ability of Lu‐177‐trastuzumab for HER2 specific tumor targeting. The conjugates were efficiently labeled with Lu‐177 with high radiochemical purity (up to 91%) and specific activity (6–13 µCi/µg). Lu‐177‐trastuzumab was stable up to 12 hr post labeling. The radioimmunoassay demonstrated good antigen binding ability and specificity for HER2 receptor protein. The patient studies showed the localization of Lu‐177‐trastuzumab at primary as well as metastatic sites (HER2 positive) in the planar and SPECT/CT images. No tracer uptake was observed in HER2 negative patients that indicated the specificity of Lu‐177‐trastuzumab. The study demonstrated that in‐house developed Lu‐177‐trastuzumab has specific targeting ability for HER2 expressing lesions and may in future become a palliative treatment option in the form of targeted radionuclide therapy for disseminated HER2 positive breast cancer.

Substantial Increase in Myocardial FDG Uptake on Interim PET/CT May Be an Early Sign of Adriamycin-Induced Cardiotoxicity.

Cumulative cardiotoxicity is a well-established adverse effect of Adriamycin therapy. Although dose dependent, cardiotoxicity has been recently reported to occur even at lower doses than usually proposed. Conventional imaging detection and/or clinical manifestation of the deterioration in cardiac function occur late in the process; thus, it is desirable to have noninvasive markers to detect toxicity at an early stage. Several biochemical markers including troponin and atrial natriuretic peptide were explored for this purpose. The present case depicts that a significant increase in myocardial FDG uptake on posttherapy PET/CT can be a potential imaging biomarker of Adriamycin-induced cardiotoxicity.

Aseptic Loosening of Elbow Prostheses Diagnosed on F-18 Fdg Pet/ct

Abstract: A 35-year-old woman, having recurrent pain after total elbow arthroplasty, was subjected to positron emission tomography/computed tomography with fluorodeoxyglucose (FDG PET/CT) to rule out infected orthopedic hardware. A diagnosis of aseptic loosening was made based on the gram staining and 9 months of clinical follow-up. This case report highlights the utility of FDG PET/CT in evaluation of painful elbow prostheses and describes the FDG uptake pattern in confirmed case of aseptic loosening.

Comparison of left ventricular phase parameters analysis between two software programs in patients with normal gated single-photon emission computed tomography-myocardial perfusion imaging

Background: Phase analysis can be easily performed by different software to assess the left ventricular dyssynchrony from gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with high precision. However, the normal values of histogram bandwidth (HBW) and phase standard deviation (PSD) and their comparison using different programs have not been fully elucidated and actively being evaluated at present. The aim of this study was to determine the phase analysis parameters values and to compare the phase indices of two commonly used programs in a group of patients with normal gated SPECT-MPI. Methods: Phase parameters were retrospectively evaluated in 138 consecutive nondiabetic patients having a normal gated SPECT-MPI using the quantitative gated SPECT (QGS) and Emory Cardiac Toolbox (ECTb) software. HBW, PSD, and phase entropy were calculated separately using both programs. Results: The fair correlation between software programs was observed. HBW and PSD in QGS and ECTb were 26.20 ± 9.7 and 25.46 ± 8.0 (r-value. 56, SEE 6.65) and 6.64 ± 2.5 and 7.65 ± 2.5 (r = 0.54, SEE 2.14), respectively. The value of phase entropy in QGS program was 45.08 ± 6.3. A fair correlation between phase entropy and PSD in QGS was observed (r = 0.44, 95% confidence interval-0.29–0.56). Conclusion: Phase analysis parameters derived from gated SPECT-MPI in patients with normal myocardial perfusion are program dependent and may differ. The results cannot be interchangeably used in the same patients.

Bone marrow hyperplasia detected by gated blood pool imaging

Technetium-99m RBC gated blood pool ventriculography study or multigated acquisition (MUGA) is a commonly employed imaging study to determine the left ventricle ejection fraction and regional wall motion. However, tracer distribution at abnormal sites requires further evaluation. We present the case of a young thalassemia patient with significant tracer uptake in the rib cage as observed in the planar images of MUGA study helping in the demonstration of scintigraphic evidence of bone marrow hyperplasia.

Evaluation of external beam hardening filters on image quality of computed tomography and single photon emission computed tomography/computed tomography.

This study was undertaken to evaluate the effect of external metal filters on the image quality of computed tomography (CT) and single photon emission computed tomography (SPECT)/CT images. Images of Jaszack phantom filled with water and containing iodine contrast filled syringes were acquired using CT (120 kV, 2.5 mA) component of SPECT/CT system, ensuring fixation of filter on X-ray collimator. Different thickness of filters of Al and Cu (1 mm, 2 mm, 3 mm, and 4 mm) and filter combinations Cu 1 mm, Cu 2 mm, Cu 3 mm each in combination with Al (1 mm, 2 mm, 3 mm, and 4 mm), respectively, were used. All image sets were visually analyzed for streak artifacts and contrast to noise ratio (CNR) was derived. Similar acquisition was done using Philips CT quality control (QC) phantom and CNR were calculated for its lexan, perspex, and teflon inserts. Attenuation corrected SPECT/CT images of Jaszack phantom filled with 444–555 MBq (12–15 mCi) of 99mTc were obtained by applying attenuation correction map generated by hardened X-ray beam for different filter combination, on SPECT data. Uniformity, root mean square (rms) and contrast were calculated in all image sets. Less streak artifacts at iodine water interface were observed in images acquired using external filters as compared to those without a filter. CNR for syringes, spheres, and inserts of Philips CT QC phantom was almost similar to Al 2 mm, Al 3 mm, and without the use of filters. CNR decreased with increasing copper thickness and other filter combinations. Uniformity and rms were lower, and value of contrast was higher for SPECT/CT images when CT was acquired with Al 2 mm and 3 mm filter than for images acquired without a filter. The study suggests that for Infinia Hawkeye 4, SPECT/CT system, Al 2 mm, and 3 mm are the optimum filters for improving image quality of SPECT/CT images of Jaszack or Philips CT QC phantom keeping other parameters of CT constant.

Scintigraphic findings in end-stage liver disease on Tc-99m sestamibi SPECT/CT myocardial perfusion imaging

Technetium-99m sestamibi myocardial perfusion imaging is commonly employed non-invasive study for evaluation of coronary artery disease; however, incidental extracardiac scintigraphic findings observed may provide additional diagnostic information. The authors present the unusual scintigraphic findings in a case of decompensated liver disease with right hepatic hydrothorax, being planned for orthotopic liver transplant.

Can 99mTc-labeled RBC-equilibrium radionuclide angiocardiography be an adjunct imaging biomarker for marrow hyperplasia in beta-thalassemia major patients?

Beta-thalassemia major (TM) is a hereditary disorder characterized by ineffective erythropoiesis owing to anomalies in beta-chain of hemoglobin and the peripheral anemia results in ineffective expansion and hyperplasia of the bone marrow. These patients require multiple tests to monitor the adequacy of blood transfusion and iron overload. Tc-labeled red blood cellequilibrium radionuclide angiocardiography (Tc RBC-ERNA) in these patients is used for monitoring of left ventricular ejection function (LVEF), along with prospect for whole-body marrow imaging as an indicator for adequacy of transfusion. CASE SUMMARY

Incidental detection of bronchial carcinoid on Tc-99m sestamibi SPECT/CT myocardial perfusion scintigraphy.

Abstract Technetium-99m sestamibi MPS is a commonly employed imaging study for myocardial perfusion; however, incidental extracardiac sestamibi uptake requires further evaluation, and the tracer uptake in the thorax/mediastinum may be pathological. The authors present a case of significant extra-cardiac uptake seen on stress MPS images helping in the incidental detection of bronchial carcinoid.

Role of 99mTc-sestamibi gated SPECT/CT myocardial perfusion imaging in the management of patients with myocardial bridging and its correlation with coronary angiography

Myocardial bridging (MB)-a congenital coronary abnormality in its severe form leads to myocardial edema, fibrosis, and ischemia due to coronary artery compression during systole and early part of the diastole. This study evaluated the hemodynamic significance of MB by detecting severity and extent of perfusion abnormality using 99mTc-sestamibi (MIBI) gated single photon emission computed tomography (SPECT)/CT myocardial perfusion imaging (MPI), its correlation with coronary angiography and role in patients management. Five patients with complaints of atypical chest pain, exertional angina, or dyspnea underwent stress/rest 99mTc-MIBI SPECT/CT MPI. The gated stress and rest SPECT/CT images on 17 segment model using quantitative gated-SPECT (QGS) softwarewere analyzed and compared with coronary angiography. Four out of five patients showed reversible perfusion defect in the left anterior descending (LAD) territory segments involved with myocardial bridging (3 patients had already proven MB; while MB was detected in 1 patient after MPI). The fifth patient with MB in the distal LAD revealed normal myocardial perfusion. All the patients were conservatively managed either due to small reversible perfusion defects or normal study except one patient. The gated SPECT/CT MPI of five patients with MB in the present study revealed their perfusion status, information on myocardial wall thickening, contractility, and ejection fraction. <Learning objective: Myocardial bridging may be one of the underlying causes for angina or sudden death even in absence of cardiovascular risk factors. The proven or clinical suspicious myocardial bridging in patients with typical/atypical chest pain and low probability of atherosclerosis should be evaluated with gated SPECT/CTMPI. It helps in detection of coronary artery disease along with severity and extent of myocardial ischemia for their further management.>.