Asia Oceania Journal of Nuclear Medicine & Biology
Volume:11 Issue: 2, Summer and Autumn 2023

The aim of this study was to assess the prognostic value of pretreatment Positron emission tomography / computed tomography using 18F-fluorodeoxyglucose (FDG-PET/CT) in cervical cancer according to two major histologic types.

Eighty-three squamous cell carcinoma (SCC) patients and 35 adenocarcinoma (AC) patients who underwent pretreatment FDG-PET/CT were retrospectively analyzed. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were calculated. Kaplan-Meier analyses were used to compare correlations between each PET parameter and overall survival (OS). The prognostic values of imaging and clinical parameters were assessed using uni- and multivariable Cox proportional hazard models.

SUVmax, SUVmean, and TLG were significantly higher in SCC than in AC (p<0.01 each). No significant difference in MTV was seen between the two groups (p=0.10). As for Kaplan-Meier analyses, in SCC, patients with SUVmax, SUVmean, MTV, and TLG exceeding cutoff values tended to show worse OS than patients with lower values (p=0.07, p=0.27, p<0.01, and p=0.01, respectively, for OS). On the other hand, in AC, patients with MTV and TLG exceeding cutoff values showed significantly worse PFS and OS (p<0.01 each for OS), while SUVmax and SUVmean were unrelated to OS (p=0.91 and p=0.83, respectively for OS). As for multivariable analyses, in SCC, TLG was identified as an independent prognostic factor for OS (p=0.01). In AC, MTV was identified as an independent prognostic factor for OS (p=0.02).

Our preliminary data suggest that FDG-PET/CT would be useful for predicting prognosis in cervical cancer, although the clinical significance of quantitative values may differ according to histopathological type.

Advanced Hodgkin Lymphoma has a higher probability of relapse and recurrence. Classical clinicopathological parameters including the International Prognostic Score (IPS) have not been reliable in predicting prognosis or tailoring treatment.  Since FDG PET/CT is the standard of care in staging Hodgkin Lymphoma, this study attempted to evaluate the clinical utility of baseline metabolic tumor parameters in a cohort of advanced Hodgkin lymphoma (stage III and IV).

Histology-proven advanced Hodgkin Patients presenting to our institute between 2012-2016 and treated with chemo-radiotherapy (ABVD / AEVD) were followed up till 2019. Quantitative PET/CT and clinicopathological parameters were used to estimate the Event Free Survival (EFS) in 100 patients. Kaplan-Meier method with log-rank test was used to compare the survival times of prognostic factors.

At a median follow-up of 48.83 months (IQR:33.31-63.05 months), the five-year-EFS was 81%. Of the 100 patients, 16 had relapsed (16%) and none died at the last follow-up. On Univariate analysis, among non-PET parameters bulky disease (P=0.03) and B-symptoms (P=0.04) were significant while among PET/CT parameters SUVmax (p=0.001), SUVmean (P=0.002), WBMTV2.5 (P<0.001), WBMTV41% (P<0.001), WBTLG2.5 (P<0.001) and WBTLG41% (P <0.001) predicted poorer EFS.  5-year EFS for patients with low WBMTV2.5 [<1038.3 cm3] was 89% and 35% for patients with high WBMTV2.5 [≥1038.3 cm3] (p <0.001). In a multivariate model, only WBMTV2.5 (P=0.03) independently predicted poorer EFS.

PET-based metabolic parameter (WBMTV2.5) was able to prognosticate and complement the classical clinical prognostic factors in advanced Hodgkin Lymphoma. This parameter could have a surrogate value for prognosticating advanced Hodgkin lymphoma. Better prognostication at baseline translates to tailored or risk-modified treatment and hence higher survival.

The prevalence of coronary artery disease (CAD) is high in patients with epilepsy using antiepileptic drugs (AED). Epilepsy, AED, or the type and duration of AED use , may contribute to higher CAD risk.In this study, myocardial perfusion imaging (MPI) was compared between patients using carbamazepine and valproate.

Out of 73 patients receiving carbamazepine or valproate monotherapy for more than 2 years, visited at a tertiary referral clinic, 32 patients participated in a 2-day stress and rest phases MPI. For each phase, 15-25 mCi 99mTc-MIBI was injected, at peak exercise or by pharmacologic stimulation for the stress phase. SPECT with cardiac gating was done by a dual-head gamma camera and processed and quantified. Scans with at least one definite reversible hypo-perfusion segment were considered abnormal.

Seventeen patients received carbamazepine monotherapy and 15 valproates. Age and duration of AED use were similar between the groups. Two scans were abnormal (6.3%) both in valproate group (13.3%). Duration of AED use was higher in patients with abnormal scans. In patients receiving monotherapy >2 years, the frequency of abnormal MPI was similar between groups (P-value=0.12).  In patients receiving monotherapy > 5 years, prevalence of abnormal MPI was higher in the valproate group (28.6% vs. 0.0%; P-value=0.042). Considering valproate subgroup, ischemic patients had higher duration of AED use, comparing with the normal patients (17.0±4.2 vs. 6.4±4.8, P-value=0.014).

MPIs were abnormal in patients receiving valproate after 5 years compared to patients receiving carbamazepine. Long-term valproate use may increase the risk of CAD.

We evaluated the impact of the COVID-19 pandemic on the number of referrals for SPECT myocardial perfusion imaging (SPECT-MPI) as well as changes in the clinical and imaging characteristics.

We respectively reviewed 1042 SPECT-MPI cases performed in a 4-month period during the COVID-19 pandemic (PAN; n=423) and compared their findings with those acquired in the same months before the pandemic (PRE; n=619).

The number of stress SPECT-MPI studies performed during the PAN period significantly dropped compared to the number of studies carried out in the PRE period (p = 0.014). In the PRE period, the rates of patients presenting with non-anginal, atypical and typical chest pain were 31%, 25% and 19%, respectively. The figures significantly changed in the PAN period to 19%, 42%, and 11%, respectively (all p-values <0.001). Regarding the pretest probability of coronary artery disease (CAD), a significant decrease and increase were noticed in patients with high and intermediate pretest probability, respectively (PRE: 18% and 55%, PAN: 6% and 65%, p <0.001 and 0.008, respectively). Neither the rates of myocardial ischemia nor infarction differed significantly in the PRE vs. PAN study periods.

The number of referrals dropped significantly in the PAN era. While the proportion of patients with intermediate risk for CAD being referred for SPECT-MPI increased, those with high pretest probability were less frequently referred. Image parameters were mostly comparable between the study groups in the PRE and PAN periods.

Due to the suitable physical characteristics of 89Zr as a PET radionuclide and affinity of Trastuzumab monoclonal antibody against HER2, [89Zr]Zr-Trastuzumab was prepared and went through preclinical evaluations for ultimate human applications.

89Zr was produced by using 89Y(p,n)89Zr reaction at a 30 MeV cyclotron (radionuclide purity>99.9%, specific activity of 17 GBq/µg). p-SCN-Bn-Deferoxamine (DFO); was conjugated to trastuzumab, followed by labeling with 89Zr in oxalate form at optimized condition. Cell binding, internalization and, radioimmuno-activity assays were studied using HER2+ BT474 and HER2- CHO cell lines. Finally, the biodistribution of the radioimmunoconjugate was assessed in normal and HER2+ BT474 tumor-bearing mice using tissue counting and imaging at different intervals after injection. Also, a woman with HER2-positive metastatic breast cancer under treatment with Herceptin underwent both [89Zr]Zr-Trastuzumab and, [18F]FDG PET/CTs.

89Zr was produced with high radionuclidic and radiochemical purities (>99%) and [89Zr]Zr-DFO-Trastuzumab was prepared with radiochemical purity of >98% and specific activity of 9.85 GBq/µmol. The radioimmunoconjugate was stable both in PBS buffer and in human serum for at least 48 h. The radioimmunoactivity assay demonstrated about 70% of [89Zr]Zr-DFO-Trastuzumab is bound to the BT474 cells at the number of 250×106 cells. Cell binding studies showed that about 28% of radioimmunoconjugate is attached to BT474 cells after 90 min. Internalization studies showed that 50% of [89Zr]Zr-Trastuzumab is internalized to BT474 cells only in 6 h. The biodistribution study of the labeled compound in normal mice demonstrated the same pattern of the monoclonal antibodies which is entirely different from the biodistribution of free 89Zr. Biodistribution and imaging studies in tumor-bearing mice showed the significant uptake values of [89Zr]Zr-Trastuzumab in tumor sites. [89Zr]Zr-Trastuzumab PET/CT revealed metastatic lesions documented previously with [18F]FDG PET/CT scan in a woman with breast cancer who was under treatment with Herceptin. Although the [18F]FDG PET/CT scan had better quality images, the valuable and unique advantage of [89Zr]Zr-Trastuzumab PET/CT is delineating HER2+ metastasis, which is essential in diagnosis and HER2-based treatments.

The prepared [89Zr]Zr-Trastuzumab has a high potential radio-pharmaceutical for immune-PET imaging of the patients with HER2+ tumors.

This study aimed to create a deep learning (DL)-based denoising model using a residual neural network (Res-Net) trained to reduce noise in ring-type dedicated breast positron emission tomography (dbPET) images acquired in about half the emission time, and to evaluate the feasibility and the effectiveness of the model in terms of its noise reduction performance and preservation of quantitative values compared to conventional post-image filtering techniques.

Low-count (LC) and full-count (FC) PET images with acquisition durations of 3 and 7 minutes, respectively, were reconstructed. A Res-Net was trained to create a noise reduction model using fifteen patients’ data. The inputs to the network were LC images and its outputs were denoised PET (LC + DL) images, which should resemble FC images. To evaluate the LC + DL images, Gaussian and non-local mean (NLM) filters were applied to the LC images (LC + Gaussian and LC + NLM, respectively). To create reference images, a Gaussian filter was applied to the FC images (FC + Gaussian). The usefulness of our denoising model was objectively and visually evaluated using test data set of thirteen patients. The coefficient of variation (CV) of background fibroglandular tissue or fat tissue were measured to evaluate the performance of the noise reduction. The SUVmax and SUVpeak of lesions were also measured. The agreement of the SUV measurements was evaluated by Bland–Altman plots.

The CV of background fibroglandular tissue in the LC + DL images was significantly lower (9.10 2.76) than the CVs in the LC (13.60  3.66) and LC + Gaussian images (11.51  3.56). No significant difference was observed in both SUVmax and SUVpeak of lesions between LC + DL and reference images. For the visual assessment, the smoothness rating for the LC + DL images was significantly better than that for the other images except for the reference images.

Our model reduced the noise in dbPET images acquired in about half the emission time while preserving quantitative values of lesions. This study demonstrates that machine learning is feasible and potentially performs better than conventional post-image filtering in dbPET denoising.

The traditional practice of empiric radioiodine (I-131) prescription is scientifically obsolete and inappropriate for inoperable metastatic differentiated thyroid cancer. However, theranostically guided prescription is still years away for many institutions. A personalized predictive method of radioiodine prescription that bridges the gap between empiric and theranostic methods is presented. It is an adaptation of the “maximum tolerated activity” method, where serial blood sampling is replaced by population kinetics carefully chosen by the user. It aims to maximize crossfire benefits within safety constraints to overcome tumour absorbed dose heterogeneity for a safe and effective first radioiodine fraction i.e., the First Strike.

The EANM method of blood dosimetry was incorporated with population kinetics, marrow and lung safety constraints, body habitus and clinical assessment of metastatic extent. Population data of whole body and blood kinetics in patients with and without metastases, prepared by recombinant human thyroid stimulating hormone or thyroid hormone withdrawal, and the maximum safe marrow dose rate were deduced from published data. For diffuse lung metastases, the lung safety limit was linearly scaled by height and separated into lung and remainder-of-body components.

The slowest whole body Time Integrated Activity Coefficient (TIAC) amongst patients with any metastases was 33.5±17.0 h and the highest percentage of whole body TIAC attributed to blood was 16.6±7.9%, prepared by thyroid hormone withdrawal. A variety of other average radioiodine kinetics is tabulated. Maximum safe marrow dose rate was deduced to be 0.265 Gy/h per fraction, where blood TIAC is normalised to administered activity. An easy-to-use calculator was developed which only requires height, weight and gender to populate recommendations for personalized First Strike prescription. The user decides by clinical gestalt whether the prescription is to be constrained by marrow or lung, then selects an activity depending on how extensive the metastases are likely to be. A Standard Female with oligometastasis and good urine output without diffuse lung metastasis is expected to safely tolerate 8.03 GBq of radioiodine as the First Strike.

This predictive method will help institutions rationalise the First Strike prescription based on radiobiologically sound principles, personalised to individual circumstances.

[68Ga] Ga-labeled C-X-C motif receptor4 as a novel radio-ligand using PET/CT has been investigated for tracing various kinds of solid and hematopoietic malignancies in recent years. High-grade Glioma (WHO classification 2016 grade III and IV) shows elevated levels of CXCR4 ligand expression in the affected tumoral cells. Healthy and non-affected organ cells express low-level CXCR4 ligands density. We performed [68Ga] Ga-Pentixafor (Pars-Cixafor™) PET/CT in a patient with high-grade Glioma (anaplastic oligodendroglioma WHO grade III) with no other documented medical condition and history. In addition to the Pentixafor-avid tumor remnant in the PET/CT images, we observed mild symmetrical bilateral uptake in the fibro glandular tissue of the breasts and moderate CXCR4(Pentixafor) avidity in both adrenal glands without any discernable pathology and abnormal density changes in the CT component of the study. Attention should be paid to the interpreting [68Ga] Ga-Pentixafor PET/CT examination and its normal uptakes and variants.

Hodgkin Lymphoma (HL) is a malignancy involving lymph nodes and lymphatic system. [18F]F-FDG PET/CT (FDG-PET) imaging is routinely used for staging, to assess early chemotherapy response (interim FDG-PET), at the end of treatment (EoT FDG-PET) and for the identification of disease recurrence.We present a case of a 39-year-old man treated for HL. FDG-PET scans performed after first line therapy (both Interim PET and at the end of therapy) demonstrated a persistent and significant mediastinal FDG uptake. The patient was treated with a second line therapy but the FDG-PET uptake did not change. After board discussion a new surgical, thoracoscopy-guided biopsy was performed. Histopathology demonstrated a dense fibrous tissue with occasional chronic inflammatory infiltrates.Persistent FDG-PET positivity may suggest refractory or relapsed disease. However, occasionally, non-malignant conditions are responsible for a persistent FDG uptake, not related to primary disease. An accurate evaluation of clinical history and previous imaging exams is mandatory for clinicians and others experts to avoid misinterpretations of FDG-PET results. Nevertheless, in some cases, only a more invasive procedure, such as a biopsy, may finally lead to a definitive diagnosis.

18F-fluorodeoxyglucose Positron emission tomography (18F-FDG PET/CT ) is now being used as a single modality for metastatic workup and response evaluation in breast cancer. An increase in metabolic activity indicates disease progression; however, metabolic flare should be kept in mind. Metabolic flare is a well-documented phenomenon reported in metastatic breast and prostate cancer. Despite a favorable response to therapy, there is a paradoxical increase in radiopharmaceutical uptake. The flare phenomenon with various chemotherapeutic and hormonal agents is well acknowledged in bone scintigraphy. However, very few cases have been documented on PET/CT. Increased uptake may be noted after treatment is instituted. The increased osteoblastic activity is associated with the healing response of bone tumors. We report a case of treated breast cancer. She presented with metastatic recurrence after four years of initial management. The patient was started on paclitaxel chemotherapy. Serial 18F- FDG PET/CT demonstrated metabolic flare and complete metabolic response.

Adrenocortical carcinoma (ACC) is a rare type of cancer that is associated with a high rate of recurrence and poor prognosis. The main diagnostic approaches to adrenocortical cancer include CT scan, MRI and the promising role of 18F-FDG PET/CT. The main therapeutic approaches include radical surgery of local disease and recurrences, as well as adjuvant mitotane therapy.The evaluation of adrenocortical carcinoma (ACC) could be difficult by using 18F-FDG PET/CT in view of the significant association between the 18F-FDG uptake and ACC. At the same time, not all adrenal glands with 18F-FDG uptake are considered to be malignant, so awareness of these various findings is substantial for ACC management, especially with limited data regarding the role of 18F-FDG PET/CT in ACC post-operative settings.This report discusses the case of a 47-year-old man with a history of left adrenocortical carcinoma who underwent adrenalectomy and received adjuvant mitotane therapy. 9 months after the surgery, a follow-up 18F-FDG PET/CT scan showed that the 18F-FDG uptake was prominent in the right adrenal gland without corresponding abnormal CT scan findings.

Graves’ disease (GD) is the commonest cause of hyperthyroidism, accounted for 70-80% in iodine sufficient countries and up to 50% in iodine deficient countries. Combination of genetic predisposition and environmental factors influences the development of GD. Graves’ orbitopathy (GO) represents the most common extra-thyroidal manifestation of GD with substantial impact on morbidity and quality of life. Expression of thyroid stimulating hormone receptor (TSHR) mRNA and protein in orbital tissues infiltrated by the activated lymphocytes produced by thyroid cells (Thyroid Receptor Antibody) results in the secretion of inflammatory cytokines that leads to the development of histological and clinical characteristics of GO. A subdivision of TRAb, thyroid stimulating antibody (TSAb), was found to have a close relationship with the activity and severity of GO, and suggested to be considered as a direct parameter of GO. Here, we present a 75-year-old female with a history of GD that has successfully been treated with radioiodine treatment, who developed GO 13 months after therapy while being hypothyroid with high TRAb level. The patient was given a second dose of radioiodine ablation to maintain GO with successful result.