Asia Oceania Journal of Nuclear Medicine & Biology
Volume:9 Issue: 2, Summer and Autumn 2021

Miltuximab® is a chimeric antibody targeting Glypican-1 (GPC-1), a cell surface antigen which is overexpressed in solid cancers. Miltuximab® has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. This first in human study used Miltuximab® radiolabelled with Gallium-67 ([67Ga]Ga-DOTA-Miltuximab®). The primary study endpoint was to establish safety and tolerability of Miltuximab®. Secondary endpoints were biodistribution, tumour targeting and pharmacokinetic analysis.

Four cohorts of three patients (9 with advanced prostate cancer, 2 with pancreatic and 1 with bladder cancer) were dosed with 1 mg, ~250 MBq of [67Ga]Ga-DOTA-Miltuximab®. Cohort 1 received [67Ga]Ga-DOTA-Miltuximab® alone, while cohorts 2-4 were pre-infused with increasing doses (3.5, 11.5 and 24 mg, respectively) of unlabelled Miltuximab®-DOTA 1 hour prior to [67Ga]Ga-DOTA-Miltuximab®. Safety and tolerability were assessed by clinical and standard laboratory assessments. Patients underwent whole body gamma-camera scans and SPECT/CT scans up to 144 h post-infusion. Total organ radiation exposure was determined by dosimetry of whole-body gamma scans.

The dosing regimen was well tolerated, with no drug-related adverse events observed. Liver and spleen uptake of [67Ga]Ga-DOTA-Miltuximab® was observed. Liver uptake was reduced by pre-infusion of unlabelled Miltuximab®-DOTA. Dosimetry analysis showed a favorable exposure profile. [67Ga]Ga-DOTA-Miltuximab® targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. Higher doses of unlabelled antibody achieved lower liver uptake and increased antibody serum half life.

This study is the first in human for Miltuximab® a first in class antibody targeting GPC-1. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab® as a theranostic agent in a planned Phase I human trial.Trial registration: ANZCTR, ACTRN12616000787482, https://www.anzctr.org.

Prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) is an emerging modality to detect metastatic disease in patients with prostate cancer (PCa). This prospective study aimed to evaluate the role of [68Ga]-PSMA PET/CT in the initial workup of intermediate and high-risk PCa . Twenty-five patients with newly transrectal ultrasound biopsy-proven, untreated intermediate- and high-risk PCa (mean age, 68.5±6.2 years; range 55–83 years) were enrolled in this prospective study between September 2018 and June 2020 and underwent a [68Ga]-PSMA PET/CT examination. All images were analyzed both visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax) of the primary prostatic tumor and metastatic lesions. The diagnostic sensitivity of [68Ga]-PSMA PET/CT for the diagnosis of PCa was established by histopathology as the reference standard. The associations between SUVmax of the primary tumors and prostate-specific antigen (PSA) levels, Gleason scores (GSs), and metastatic extent of the disease were studied. All patients had a positive [68Ga]-PSMA PET/CT exam. Seventeen patients (58%) showed [68Ga]-PSMA avidity in both prostate lobes and 8 (32%) had unilateral uptake. SUVmax in the primary tumor significantly correlated with serum PSA values (r=0.57, P=0.003). PSMA PET/CT depicted regional lymph node metastases in 32% of patients, distant lymph node metastases in 20%, osseous metastases in 16% and pulmonary metastases in 8% of patients. Sixty percent of PSMA-positive bone metastases and 21.4% of intraprostatic tumoral lesions were missed on the contemporaneous bone scintigraphy and magnetic resonance imaging, respectively. [68Ga]-PSMA PET/CT shows promise as a valuable imaging modality with high diagnostic sensitivity in the setting of intermediate and high-risk PCa. Moreover, the SUVmax of the primary tumor has a positive correlation with PSA levels at the time of the scan.

Only few studies have assessed the use of gallium citrate-67 single-photon emission computed tomography/computed tomography (67Ga-SPECT/CT) for localizing the foci of classic fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Hence, the current study aimed to assess the diagnostic contribution of 67Ga-SPECT/CT in a tertiary referral setting where nuclear imaging tests are performed after an unsuccessful comprehensive primary diagnostic workup. We retrospectively assessed the medical records of 27 adult patients with FUO/IUO who had an unsuccessful diagnostic workup and who underwent 67Ga-SPECT/CT for the localization of FUO/IUO foci in our university hospital between 2013 and 2019. The primary outcome was diagnostic yield. The secondary outcomes were overall clinical efficacy and spontaneous remission of FUO/IUO symptoms in patients with a negative 67Ga-SPECT/CT finding. Almost all patients completed the recommended diagnostic workup, except for urine culture and abdominal ultrasonography. Moreover, prior to 67Ga-SPECT/CT, all patients underwent thoraco-abdominopelvic CT scan, which was a non-diagnostic procedure. After a median follow-up of 843 days, the cause was identified in 16 (59%) patients. 67Ga-SPECT/CT successfully localized the FUO/IUO foci in eight patients (diagnostic yield = 30%; 95% confidence interval [CI]: 14%–50%). However, the causes remained unknown during follow-up in 11 (41%) patients. Among them, five experienced spontaneous regression of symptoms. 67Ga-SPECT/CT was negative in four of the five patients with spontaneous regression in symptoms without a definite cause. Considering this an important event, the overall clinical efficacy of 67Ga-SPECT/CT increased to 44% (95% CI: 25%–65%). 67Ga-SPECT/CT had an acceptable diagnostic yield for the localization of FUO/IUO foci, which are challenging to diagnose, in a contemporary tertiary referral care setting. In patients who experienced spontaneous regression in symptoms with an unexplained cause, the absence of abnormal uptake might indicate prospective spontaneous remission. Thus, 67Ga-SPECT/CT could be an active first-line nuclear imaging modality in settings where fluorine-18-fluorodeoxy glucose positron emission tomography and computed tomography is not available for the assessment of FUO/IUO causes.

The purpose of this study was to investigate regional cerebral blood flow (rCBF) reduction in patients with dizziness and perfusion-related clinical impairment using brain perfusion single photon emission tomography (SPECT). Thirty-four patients with subjective dizziness and 13 age- and sex-matched healthy controls were studied. Dizziness-related impairments were assessed using the Dizziness Handicap Inventory (DHI) and Short Physical Performance Battery (SPPB). Brain perfusion SPECT scan was acquired from all participants. The carotid intima-media thickness (CIMT) was also measured. Brain perfusion data were qualitatively interpreted in all cases. Voxel-wise analysis was also conducted in 11 patients compared to healthy controls. Thirty-four patients (mean age=53.8±13.4 years, m/f: 19/15) and 13 age- and sex-matched controls (mean age=51.5±13.1, m/f: 7/6) were included. The dizziness severity was mild in 58.8% (n=20), moderate in 26.5% (n=9), and severe in 14.7% (n=5). Qualitative interpretation of SPECT images showed normal scans in 4 (11.2%) patients and abnormal scans in 30 (88.2%) patients. Patients with dizziness showed a significantly decreased brain perfusion in the precuneus, cuneus, occipital lobe (superior and inferior parts), frontal lobe (inferior and middle parts), temporal lobe, parietal lobe (inferior and superior parts), cerebellum, insula, and putamen nucleus. Based on both qualitative SPECT interpretation and voxel-wise analysis, perfusion defect had a significant association with the total SPPB score and the scores of two sub-domains (p<0.05), but not with the DHI (p>0.05) score . The perfusion- and atherosclerosis-related impairments of gait and balance were largely independent of subjective dizziness and dizziness severity. Moreover, this study provided support for contribution of perfusion impairment to the disturbance of gait and balance in older populations along with other pathologic processes.

Ra-223 is a promising radionuclide for the treatment of skeletal metastases in castration-resistant prostate cancer patients. This study aims to estimate the lower limits for feasible Ra-223 single-photon emission computerized tomography (SPECT) imaging using a Monte Carlo simulation study . The SPECT images were produced on a homemade code: the Monte Carlo simulation of electrons and photons for SPECT (MCEP-SPECT). The National Electrical Manufacturers Association (NEMA) phantom with six hot spheres of diameters of 37, 28, 22, 17, 13, and 10 mm installed inside, was used. The background activity concentration was 0.6 kBq/mL, and the ratios of hot concentrations to the background (RHB) were 25, 20, 15, 10, and 5. When RHB was 15, the background concentrations of 1.5, 0.9, 0.3, and 0.15 kBq/mL were also tested. The energy window was 84 keV±10%. The number of projections was 60/360°, and the acquisition time was 60 s per projection. Two kinds of collimators: middle-energy general-purpose (MEGP) and high-energy general-purpose (HEGP), were examined. The SPECT images were evaluated based on two quantitative indexes: contrast-to-noise ratio (CNR) for detectability and contrast recovery coefficient (CRC) for quantitative accuracy . The CRC for the HEGP collimator was 35–40%, while the CRC for the MEGP collimator was 25–30%. The CNRs for the MEGP collimator were larger than those for the HEGP collimator. The CNRs of the hot spheres with diameters less than 22 mm were lower than 5.0 for both collimators, when RHB and the background concentration were 15 and 0.6 kBq/mL, respectively. Based on the obtained results, it was estimated that the lower limit of RHB for the detection of the hot sphere with a diameter of 37 mm would be approximately 20 if the background concentration is 0.05 kBq/mL. The MEGP collimator is superior in terms of detectability, while the HEGP collimator is superior in terms of quantitative accuracy. When the lesion size is small, the MEGP collimator may be favorable. Based on these results, the estimated lower limit of the activity concentration would be approximately 1 kBq/mL if the background concentration is 0.05 kBq/mL for a large lesion.

To assess respiratory-gated (RG) positron emission tomography (PET) acquisition for patients with liver metastases during delayed PET/computed tomography (CT) scanning with fluorine-18-fluorodeoxyglucose (18F-FDG).

Nineteen patients with liver metastases who had undergone early whole-body 18F-FDG PET/CT scans without the RG technique and delayed scans with the RG technique were retrospectively selected. The maximum standardized uptake value (SUVmax) of 41 liver lesions and the tumor-to-liver uptake ratios (TLRs) for these same lesions were compared among three data sets: early non-respiratory-gated (early non-RG) images, delayed non-respiratory-gated (delayed non-RG) images, and delayed respiratory-gated (delayed RG) images. In the delayed non-RG and delayed RG images, the improvements in the TLR, relative to the early non-RG images, were assessed according to lesion size.

For liver lesions, the SUVmax of early non-RG, delayed non-RG, and delayed RG images were 6.58±2.34, 7.69±3.08, and 9.47±3.73, respectively. There were significant differences among the three images (P<0.01). The TLR of the delayed RG images was significantly higher than those of the early non-RG and delayed non-RG images (P<0.01). In the delayed RG images, the difference in the TLR improvement for lesions ≤10 mm in size was 15% higher than that for lesions >10 mm in size; in the delayed non-RG images, the difference in the TLR improvement for the same lesion categories was 6%.

Delayed RG imaging improves the TLR, compared with early non-RG and delayed non-RG imaging, especially for small lesions. RG PET acquisition may be a promising protocol for assessing liver metastases on delayed PET/CT scans.

Computed tomography (CT) images are used for precise anatomical location of lesions and for accurate attenuation correction in single-photon emission computed tomography (SPECT) image reconstruction in SPECT/CT examination. The aim of this study was to verify the effects of varying CT collimation width and slice thickness on CT images and on CT attenuation corrected SPECT images. We acquired SPECT/CT images of a micro-coin phantom and the National Electrical Manufacturers Association body phantom filled with 99mTc-pertechnetate while varying the abovementioned CT parameters. The full width at half maximum of the slice sensitivity profile, the standard deviation of CT image background noise, and the radiation dose from CT scans were evaluated. Subsequently, the percentage contrast, background variability, and absolute recovery coefficient of the SPECT image were measured. Furthermore, we retrospectively reviewed the clinical bone SPECT images of 23 patients, and statistical testing of differences was performed. As the collimation width and reconstruction slice thickness of the CT image increased, z-axis resolution deteriorated, and background noise decreased. In addition, CT radiation dose decreased with increasing collimation width. Meanwhile, SPECT image quality and quantitative accuracy were unchanged with varying CT collimation width and slice thickness. There were no notable variations in clinical SPECT images and no statistically significant differences. When high-resolution CT slices on the z-axis are not required for clinical diagnosis, increasing collimation width or slice thickness can reduce the radiation dose and image noise with no influence on the quality of SPECT images.

Combined positron emission tomography/computed tomography (PET/CT) has gradually advanced with the introduction of newly developed techniques. However, the recent status of imaging techniques (e.g., scanning range, availability of correction methods, and decisions on performing delayed scan) in oncologic PET/CT with 18F-fluorodeoxyglucose (18F-FDG) in Japan is unclear. We conducted a nationwide cross-sectional survey to document 18F-FDG PET/CT protocols and clarify the recent status of imaging techniques for oncologic 18F-FDG PET/CT in Japan.

We conducted a web survey hosted by the Japanese Society of Radiological Technology between October and December 2017. The questionnaire included nine items on the demographics of the respondents, their scan protocols, and additional imaging to their routine protocols.

We received responses from 119 Japanese technologists who performed 18F-FDG PET/CT in practice. Almost all the respondents stated that the scanning range was from the top of the head to the pelvis or mid-thigh region. Newly developed techniques were used by fewer than half of the respondents. Most respondents performed additional imaging in consultation with physicians, such as delayed imaging (83%) or an extended scanning range for early imaging (55%).

Our survey helps in clarifying the recent state of oncologic 18F-FDG PET/CT imaging techniques in Japan. Given that 18F-FDG PET/CT practices most frequently performed additional imaging along with their routine scan protocol, the practice constitutes the most varied examination performed in Japanese nuclear medicine.

Brain metabolic imaging using 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) with contemporaneous low-dose CT may be used to assess neurodegenerative diseases. In contrast to oncology whole-body FDG PET, qualitative assessment alone in brain FDG PET is subjective and vulnerable to visual interference due to high physiologic background activity. Therefore, mild changes in brain metabolism may be visually undetectable by qualitative interpretation alone, resulting in diagnostic inaccuracy. To overcome this, some institutions may employ an objective comparison to a normal reference database. To date, there is limited literature describing brain metabolic changes in rare genetic neurodegenerative diseases such as Niemann-Pick disease Type C, spinocerebellar ataxia and Huntington disease. In this case series, we illustrate the typical FDG PET findings in the cortex and deep grey matter for these rare diseases, utilising normal database comparison including three dimensional Stereotactic Surface Projection (3D-SSP) mapping. These comparisons can generate 3D-SSP maps where metabolic changes may be expressed in standard deviations from normal (z-score) and visually depicted in a scale of colours to improve diagnostic accuracy.

A 65-year-old man presented with intermittent abdominal pain for three months. Abdominal ultrasonography revealed a mass in the body of the pancreas. Moreover, abdominal contrast-enhancing computed tomography revealed a homogenously enhancing mass in the body of the pancreas. Scan findings were in favor of the neuroendocrine tumor, and the serum chromogranin level was slightly raised (111.9 ng/ml, normal <98). He had no history of vomiting, jaundice, melena, hematemesis, constipation, diarrhea, weight gain, weight loss, loss of appetite, and fever. He also had no symptoms related to the excessive production of catecholamines, such as hypertension. The patient was referred for Ga-68 DOTANOC positron emission tomography-computed tomography (Ga-68 DOTANOC PET-CT) for further evaluation. The scan was done to rule out metastatic disease or other synchronous lesions to plan surgical excision. The Ga-68 DOTANOC PET-CT revealed a pancreatic lesion with no other abdominal lesions. We noted multiple tracer avid soft tissue lesions on both sides of the neck that were not diagnosed previously. This case report demonstrates a rare case with multiple paragangliomas diagnosed by the Ga-68 DOTANOC PET-CT. This finding could lead to changes in patient management.

The effectiveness of the sentinel lymph node mapping in patients with Urothelial carcinoma of the bladder is under investigation. Single photon emission computed tomography (SPECT/CT) and intraoperative sentinel node biopsy using gamma probe are performed to detect the exact location of the sentinel lymph node to be dissected during the surgery. In this case report, a 73-year old man with high grad urothelial carcinoma was referred to our nuclear medicine department for SPECT/CT, four hours after injection of the radiotracer through cystoscopy . SPECT/CT could not reveal any sentinel node; however, one sentinel lymph node was detected and harvested in the right external iliac region during surgery. SPECT/CT revealed unusual accumulation of tracer in large bowel which was due to sever adhesion of rectum and bladder, and inadvertent injection of the radiotracer into the rectal wall . During the sentinel lymph node procedure, the tracer should be injected with extreme caution and lymphoscintigraphy post injection may help detection of any injection failures.

Prostate cancer is considered to be the most common solid cancer affecting men worldwide and leading to a significant morbidity and mortality. Metastases are usually seen in bone or lymph nodes. For recurrent disease, PET imaging with 68GaPSMA-11 (also known as HBED-CC, Glu-urea-Lys(Ahx)-HBED-CC, and PSMAHBED-CC) is widely used. However, preparation of 68Ga-PSMA ligand requires the presence of radiochemistry facilities and can therefore not be utilized in centers lacking such facilities. Recently, copper labeled prostate-specific membrane antigen positron emission tomography (64Cu-PSMA PET/CT) demonstrated promising results in patients with recurrent disease and in the primary staging of selected patients with progressive local disease. In the present case, a rare manifestation site of a metastatic lesion in a patient with advanced prostate cancer is detected by 64Cu-PSMA PET/CT.

Although 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is an established method for the staging of malignancies, benign lesions (e.g, active inflammatory lesions) often show increased metabolic activity. Herpes zoster is the clinical manifestation of the activation and replication of dormant varicella-zoster virus (VZV) in individuals with decreased cell-mediated immunity. Although the diagnosis of herpes zoster is clinical, it is sometimes observed incidentally during imaging for another disease. We describe the case of a 67-year-old Japanese female patient diagnosed with cervical cancer in whom FDG-PET/CT revealed herpes zoster manifestations: hypermetabolic cutaneous lesions in the buttock and pelvic lymph node involvement. The resected lymph nodes showed no malignant lesions but revealed lymphoid follicle formation, probably related to viral infection. There has been no report comparing FDG-PET findings of lymph nodes with histologic findings; the present findings are compatible with a clinically VZV-induced inflammatory reaction in regional lymph nodes, which increased FDG accumulation. Active infection with VZV displays increased FDG uptake in regional lymph nodes and may lead to incorrect malignant disease management in oncology. Misdiagnoses can be avoided by a careful interpretation by experienced nuclear medicine physicians as well as proper clinical evaluation.

Epilepsy is a disorder of the brain, which is characterized by recurrent epileptic seizures. These patients are generally treated with antiepileptic drugs. However, more than 30% of the patients become medically intractable and undergo a series of investigations to define candidates for epilepsy surgery. Nuclear Medicine studies using Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) radiopharmaceuticals are among the investigations used for this purpose. Since available guidelines for the investigation of surgical candidates are not up-to-date, The Nuclear Medicine Society of Thailand, The Neurological Society of Thailand, The Royal College of Neurological Surgeons of Thailand, and The Thai Medical Physicist Society has collaborated to develop this Thai national guideline for Nuclear Medicine study in epilepsy. The guideline focuses on the use of brain perfusion SPECT and F-18 fluorodeoxyglucose PET (FDG-PET), the mainly used methods in day-to-day practice. This guideline aims for effective use of Nuclear Medicine investigations by referring physicians e.g. epileptologists and neurologists, radiologists, nuclear medicine physicians, medical physicists, nuclear medicine technologists and technicians.

Nuclear medicine history has its share of captivating personalities, controversial claims, and forgotten pioneers. Publications and documents that came out relatively recently, provide us with new perspectives on its history. Primary sourced material might contradict some of the long-held beliefs of the reader who only has a casual familiarity with the events, including basics such as who discovered radioactivity.Because of the nature of the specialty, the importance of the contributions of colleagues in related fields, like physics and chemistry, cannot be overstated. Many of the important discoveries were marked by serendipity, but the pioneers must be given credit for having the necessary insights to interpret the new phenomena correctly, sometimes turning perceived “failure” into novel scientific principles. In addition, most of our pioneers had to deal with inadequate facilities and funding, religious and racial discrimination, and even misogynism.The early history of nuclear medicine is presented in this article as a series of its most interesting anecdotes, from the early work on radioactivity, to the conception of the tracer principle, until the development of radioactive iodine therapy.

This quiz is part of a series which aims to aid nuclear physicians in interpreting the computed tomography (CT) component of the single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies. The current quiz includes normal and pathological axial CT images at the level of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV). The SMV is normally located to the right of the SMA and is of a larger caliber. Various pathologies such as malignancy, infection or vascular disease can alter the position and/or appearance of the SMA, SMV and the surrounding anatomical structures present at this level. Understanding how normal anatomy is altered by pathology at this level will facilitate improved interpretation of abdominal CT images.