Iranian Journal of Nuclear Medicine
Volume:24 Issue: 1, Winter-Spring 2016

Gallium-68 a positron emitter radionuclide, with great impact on the nuclear medicine, has been widely used in positron emission tomography (PET) diagnosis of various malignancies in humans during more recent years especially in neuroendocrine tumors (NETs). The vast number of 68Ge/68Ga related generator productions, targeting molecule design (proteins, antibody fragments, affibodies, peptides and small molecules), as well as existing numerous human clinical trials at the registration, continuation and completion levels, are indicative of great importance and future impact of gallium-68 radiopharmaceuticals in human health. A concise review on the recent production and application of 68Ga-tracers with the emphasis on the peptides, biomolecules and also small molecules available for clinical applications, clinical trials or preclinical studies are presented. The importance of Ga-68 radionuclide as a theranostic radionuclide with potential coupling application with therapeutic radioisotopes (such as 90Y and 177Lu) is increasing appreciated. This review describes the present status of availability, application and future horizons on the development of 68Ga-radiopharmaceuticals worldwide.

Myocardial ischemia (MI) resulting in infarction is an important cause of mortality and morbidity worldwide. Acute ischaemia rapidly impairs myocardial contractile function. Myocardial dysfunction persisting for several hours after transient non-lethal ischaemia, eventually resulting in full functional recovery is termed as myocardial stunning. Hibernation is now thought to be the consequence of repetitive bouts of ischaemia and stunning due to normally occurring increases in myocardial metabolic demand in the setting of significant coronary stenoses.We need robust investigations to identify and treat MI early. Myocardial perfusion imaging has established itself as the earliest investigation that can identify ischemia with or without infarction in an acute setting. However, recent data reveals that metabolic changes precede perfusion abnormalities during an ischemic or infarction episode; thus the renewed interest in the myocardial metabolic imaging. Concept of myocardial metabolic imaging is gaining momentum with the wider availability of positron emitting radio isotopes. Myocardial metabolism has been widely studied using 123I-BMIPP [15-(p-Iodophenyl)-3-methylpentadecanoic acid] and BMIPP was synonymous for ischemic memory imaging, (IMI). It was based on the fact that one can capture the still picture of the ongoing ischemic insult as a “memory image” past the acute episode. BMIPP imaging was primarily based on its ability to memorize the area at risk for a couple of weeks, even after reperfusion therapy. We aim to elaborate in this review the various radiotracers that can be used to identify myocardial metabolic disorders at its inception so that it may be possible to provide early management options.

Renal length measurement is an important diagnostic clue in several urinary tract abnormalities. Although ultra sonography is the most frequent used modality for renal size estimation, renal diameter assessment by 99mTc-DMSA scintigraphy is of great value. By now, pointing to the renal size in the 99mTc-DMSA scintigraphy report has not been recommended by guidelines. If the validity of 99mTc-DMSA scan for renal size assessment would be established and reported in routine clinical practice, it might be more helpful for diagnostic purposes obviating further modality use in kidney diameter assessment. 70 patients (25 males and 45 females) with the age range of 1 month to 78 years old (Mean ± SD = 18.1 ± 19.3) were included in the study. The longest axis diameter of each kidney was calculated by ultra sonography and planar 99mTc-DMSA scintigraphy. The difference in renal size estimation between US and different projections of 99mTc-DMSA scan was assessed using generalized linear model repeated measurement, pair wise comparison in Post Hoc and Bland-Altman analysis. 16 (22.9%) reports were interpreted as normal study, while 54 patients had abnormality at least in one kidney. No significant difference was noticed between the kidney diameters in US as compared to the all views of 99mTc-DMSA scan. Only in the estimation of left kidney size using 99mTc-DMSA scan, there was significant difference between anterior and posterior oblique views as well as between lateral and posterior oblique views. Mean value of the differences (estimated bias) doesnt differ significantly from 0 on the basis of 1-sample t-test. 99mTc-DMSA scintigraphy is an accurate method for renal length measurement with excellent agreement with ultra sonography. Kidney length can be easily measured as a routine processing procedure of a 99mTc-DMSA scan and not only used for more accurate interpretation of the images but also added to the final report as valuable incremental information.

Optimized production and quality control of 68Ga-DOTATATE as an efficient and preferable PET radiotracer for somatostatin receptor imaging in neuroendocrine tumors is of great interest. In this study effort has been made to present a fast, efficient, cost-effective and facile protocol for 68Ga-DOTATATE productions for clinical trials. 68Ga-DOTATATEwas prepared using generator-based [68Ga] GaCl3 and DOTATATE at optimized conditions for time, temperature, ligand amount, gallium content and column cartridge purification followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 120 min. 68Ga-DOTATATE was prepared at optimized conditions in 7-10 min at 95°C followed by SPE using C18 cartridge (radiochemical purity»99±0. 88% ITLC, >99% HPLC, specific activity: 1200-1850 MBq/nM). The biodistribution of the tracer demonstrated high kidney uptake of the tracer in 10-20 min consistent with reported somatostatin receptor mappings. The entire production and quality control of 68Ga-DOTATATE is presented including labeling, purification, HPLC analysis, sterilization and LAL test) took 18-20 min with significant specific activity for administration to limited number of patients in a PET center.

Spatial dose distribution around the radionuclides sources is required for optimized treatment planning in radioimmunotherapy. At present, the main source of data for cellular dosimetry is the s-values provided by MIRD. However, the MIRD s-values have been calculated based on analytical formula in which no electrons straggling is taken to account. In this study, we used Geant4-DNA Monte Carlo toolbox to calculate s-values and the results were compared to the corresponding MIRD data. Similar to MIRD cell model, two concentric spheres representing the cell and its nucleus were used as the geometry of simulation. The cells were assumed to be made of water. Cellular s-values were calculated for three beta emitter radionuclides 131I, 90Y and 177Lu that are widely used in radioimmunotherapy. Few lines of code in C++ were added into Geant4-DNA codes to automatically calculate the s-values and transfer data into excel files. The differences between two series of data were analyzed using Pearson’s correlation and Bland-Altman curves. We observed high correlation (R2>0.99) between two series of data for self-absorption; however, the agreement was very weak and Wilcoxon signed rank test showed significant difference (p-value<0.001). In cross-absorption, Bland-Altman analysis showed a considerable bias between MIRD s-values and corresponding Geant4-DNA data. The percent differences between the data were -79% to +67%. Results of the comparison show a reflection of systematic error rather than statistical fluctuation. The inconsistency is most probably associated with the neglecting of straggling and δ-ray transport in MIRD analytical method.

The endemic occurrence of new strains of tuberculosis around the globe has initiated new research on developing diagnostic radiopharmaceutical based on antibiotics. Tc-99m labeled streptomycin was prepared using freshly milked 99mTcO4- and various concentrations of streptomycin, stannous chloride at various temperatures in high yield radiochemical purity shown by HPLC/RTLC. At various pHs tested (3-10) the best labeling yield at optimized conditions were at 6-8 range, however pH.7 was considered the best. The radiochemical purity at the best optimized conditions was >95% as shown by RTLC and >97% using HPLC (specific activity; 1-3 GBq/mmole). The tracer proved to be stable in the final product and in presence of human serum at 37°C up to 2h. However, biodistribution and high resolution SPECT studies in wild type mice showed instability of the complex due to high stomach and thyroid activity uptake. Regardless the reported methods in the literature the direct 99mTc-labeling of aminoglycosides did not proved a suitable tracer.

Occupational exposure to ionizing radiation due to medical activities (both diagnostic and therapeutic procedures) has increased sharply in recent years. Among the occupationally exposed workers in these fields, those most affected by this increased exposure to ionizing radiation are nuclear medicine workers. In this study, annual average effective dose, annual collective effective dose, the individual dose distribution ratio, collective dose distribution ratio, frequency of dose ranges of workers in nuclear medicine departments of Bangladesh during the period 2010-2014 are presented and discussed. Annually about 300 workers of nuclear medicine departments were monitored using thermoluminescent dosimeters (TLDs). The TLDs were readout using Harshaw TLD readers (Model-4500 and Model 6600 plus) for quarterly basis to evaluate the whole-body doses of workers. The annual average effective doses of workers are well below the annual average dose limit prescribed by national regulations and international organizations. Majority (95%) of workers received doses less than 1 mSv and only 0.33% workers received doses higher than 10 mSv. The annual average effective dose of workers is three times lower than the worldwide average effective dose quoted by UNSCEAR. However, the annual average effective dose of monitored workers is comparable to dose received by workers in Turkey and France. The status and trends in occupational doses show that radiation protection at the majority of the workplace is satisfactory. In spite of that, additional measures are required due to large variations observed in the maximum individual doses over the last 5 years.

Recently, due to the special characteristics of 166Ho and chitosan, 166Ho-chitosan complex was developed for treatment of tumors such as hepatocellular carcinoma. This complex has been lately prepared with high radiochemical purity in our lab. The preclinical studies of the complex however should be performed to evaluate the tracer concentration in target and normal tissues before human use. In this study, 166Ho-chitosan was prepared and its preclinical studies for treatment of hepatocellular carcinoma was carried out by injection of the radiopharmaceutical into the rabbit`s liver via two different methods, surgery and venography. Leakage of the injected activity from the injection site in the rabbit organs was investigated using SPECT and SPECT-CT imaging up to 24 hours. Both SPECT and SPECT-CT imaging of the rabbits showed that there was no significant leakage of the injected activity. Almost all the activity would remain in the injection site at least 24 h post injection. Considering all of the excellent features of the complex, this radiopharmaceutical is suggestive for treatment of hepatocellular carcinoma by radioembolization method.

18F-Choline PET-CT is an increasingly used technique in patients with prostate cancer. The main indication is to localise the disease in patients with biochemical recurrence. To accurately interpret 18F-Choline PET, knowledge of normal tracer distribution is paramount. The aim of this study was to describe the normal distribution pattern of 18F-Choline by measuring the maximum standardized uptake values (SUVs) of various organs. 18F-Choline PET was performed in ten consecutive patients. Approximately 370 MBq of tracer was injected intravenously and a low amperage CT scan was performed for attenuation correction of PET images.Maximum SUVs were calculated on the reconstructed images for various organs. These SUVmax values depend on multiple factors and could be variable depending on the reconstruction CT methods, acquisition time and region of interest (ROI) parameters. Physiologic symmetric increased tracer uptake was noted in the salivary glands and parotid glands. Intense physiological uptake was present in the liver, pancreas, duodenum, stomach, kidneys and urinary bladder and moderate to intense uptake in the sublingual glands, lacrimal glands, nasal mucosa, thyroid gland, tonsils, adrenal glands, large bowel, bone marrow and spleen. Low-grade-to-moderate uptake was present in the choroid plexus, pituitary gland, soft palate, pharynx, left myocardium, lungs, mediastinal blood pool, testicles and muscles. Prostate and prostatic beds were excluded from the volumes of interest. This study is the first one to describe a normal range of SUVmax values for 18F-Choline PET in various organs.

We present a 55-year old male patient who was subjected to whole body skeletal scintigraphy for metastatic work up of urinary bladder cancer. Whole body 99mTc-methylene diphosphonate (MDP) skeletal scintigraphy was performed. That revealed no skeletal metastasis in the entire body skeleton and normally visualized left kidney with empty right renal fossa. Additionally tracer activity collected in pelvic region giving impression of ectopically placed kidney. To rule out ectopic pelvic kidney 99mTc-DMSA (Di-mercaptosuccinic acid) renal cortical imaging was performed. The cortical scintigraphy revealed bean shape tracer activity in pelvis simulating kidney, in addition to normal left kidney. However faint tracer activity is also localized in the right renal fossa. To differentiate malfunctioning kidney, gall bladder or intestinal tracer activity Single photon emission tomography/computed tomography (SPECT/CT) was acquired and images revealed abnormal tracer collection in pelvis was a localized urinary tracer activity in bladder and right kidney was small with impaired function.

Skeletal involvement is the second most common site of metastases after lymph nodal metastases in patients with prostate cancer. The skeletal metastases from prostate cancer are osteoblastic in nature and show increased tracer avidity on the bone scan. Focal tracer avid lesion in skeleton especially in skull requires the careful examination by further investigation. The patients with skull metastases are commonly asymptomatic at presentation, but some may have the mass lesion effect. The occurrence of solitary skull metastatic lesion is rare and the metastasis in the existing tracer uptake should be ruled out with the help of high resolution or hybrid imaging modality. We present a known case of prostate cancer who presented with pain in the right temporal region and highlight the utility of the single photon emission computed tomography/computed tomography (SPECT/CT) imaging in localization and characterization of the isolated focal tracer uptake in the skull region found in bone scan.