Current Status of PSMA‑Targeted Radioligand Therapy in the Era of Radiopharmaceutical Therapy Acquiring Marketing Authorization / 대한핵의학회잡지

Prostate-specific membrane antigen (PSMA) is highly expressed in PCa, which gradually increases in high-grade tumors, metastatic tumors, and tumors nonresponsive to androgen deprivation therapy. PSMA has been a topic of interest during the past decade for both diagnostic and therapeutic targets. Radioligand therapy (RLT) utilizes the delivery of radioactive nuclides to tumors and tumor-associated targets, and it has shown better efficacy with minimal toxicity compared to other systemic cancer therapies. Nuclear medicine has faced a new turning point claiming theranosis as the core of academic identity, since new RLTs have been introduced to clinics through the official new drug development processes for approval from the Food and Drug Administration (FDA) or European Medical Agency. Recently, PSMA targeting RLT was approved by the US FDA in March 2022. This review introduces PSMA RLT focusing on ongoing clinical trials to enhance our understanding of nuclear medicine theranosis and strive for the development of new radiopharmaceuticals.

Prognostic influence of Korean public medical insurance system on breast cancer patients

PURPOSE: To investigate the prognostic influence of Korean public medical insurance system on breast cancer patients. METHODS: Data of 1,068 patients with primary invasive breast cancer were analyzed. Korean public medical insurance status was classified into 2 groups: National Health Insurance and Medical Aid. Kaplan-Meier estimator and Cox proportional hazards model were used for survival analysis. RESULTS: The Medical Aid group showed worse prognoses compared to the National Health Insurance group both in overall survival (P = 0.001) and recurrence-free survival (P = 0.006). The Medical Aid group showed higher proportion of patients with tumor size > 2 cm (P = 0.022), more advanced stage (P = 0.039), age > 50 years (P = 0.003), and low education level (P = 0.003). The Medical Aid group showed higher proportion of patients who received mastectomy (P < 0.001) and those who received no radiation therapy (P = 0.013). The Medical Aid group showed a higher rate of distant recurrence (P = 0.014) and worse prognosis for the triple negative subtype (P = 0.006). Medical insurance status was a significant independent prognostic factor in both univariate analysis and multivariate analysis. CONCLUSION: The Medical Aid group had worse prognosis compared to the National Health Insurance group. Medical insurance status was a strong independent prognostic factor in breast cancer. Unfavorable clinicopathologic features could explain the worse prognosis for the Medical Aid group. Careful consideration should be given to medical insurance status as one of important prognostic factors for breast cancer patients.

Findings of Single-Photon Emission Computed Tomography and Its Relation with Quantitative Coronary Angiography in Patients with Significant Stenosis of the Left Main Coronary Artery

OBJECTIVE: Unrecognized left main coronary artery disease (LMCD) is often fatal; however, accuracy of non-invasive tests for diagnosing LMCD is still unsatisfactory. This study was performed to elucidate single-photon emission computed tomography (SPECT) detection of LMCD using quantitative coronary angiography (QCA) data. MATERIALS AND METHODS: Fifty-five patients (39 men; mean age, 68.1 ± 10.9 years) diagnosed with significant left main (LM) stenosis (≥ 50%) by invasive coronary angiography (ICA) were retrospectively reviewed. All study patients underwent SPECT with pharmacologic stress within 30 days of ICA. All coronary lesions were quantified via QCA, and SPECT findings were compared with QCA results. RESULTS: Only four patients (7.3%) had isolated LMCD; all others had combined significant stenosis (≥ 70%) of one or more other epicardial coronary arteries. Patients with more severe coronary artery disease tended to have higher values for summed difference scores in a greater number of regions, but the specific pattern was not clearly defined. Summed stress score of SPECT did not differ according to LM stenosis severity. Only three patients (5.4%) had a typical LM pattern of reversible perfusion defect on SPECT. A significant negative linear correlation between stenosis severity and stress perfusion percent was found in the left anterior descending artery region (r = −0.455, p < 0.001) but not in the left circumflex artery. CONCLUSION: Single-photon emission computed tomography findings were heterogeneous, not specific and poorly correlated to QCA data in patients with significant LMCD. This may be due to highly prevalent significant stenosis of other epicardial coronary arteries.

Prostate-Specific Membrane Antigen PET Imaging in Prostate Cancer: Opportunities and Challenges

The aim of this systematic review was to describe the characteristics of prostate-specific membrane antigen (PSMA)-targeting PET and their clinical applications in prostate cancer patients. There have been major strides in the design, synthesis of PSMA-targeting PET tracers over the past several years. PSMA-targeting PET tracers can be categorized, according to positron emitters and targeting strategies for the PSMA. The majority of PSMA PET studies has been focused on patients with biochemical recurrence, but additional values of PSMA PET have also been investigated for use in primary staging, treatment planning, response evaluation, and PSMA radioligand therapy. PSMA PET is expected to bring improvements in the management of patients, but the impact of improved diagnosis by PSMA on overall survival remains unanswered. Many challenges still await PSMA PET to expedite the use in the clinical practice. At this early stage, prospective multicenter trials are needed to validate the effectiveness and usefulness of PSMA PET.

Influence of Androgen Deprivation Therapy on the Uptake of PSMA-Targeted Agents: Emerging Opportunities and Challenges / 대한핵의학회잡지

Prostate-specific membrane antigen (PSMA) is an attractive target for both diagnosis and therapy because of its high expression in the vast majority of prostate cancers. Development of small molecules for targeting PSMA is important for molecular imaging and radionuclide therapy of prostate cancer. Recent evidence implies that androgendeprivation therapy increase PSMA-ligand uptake in some cases. The reported upregulations in PSMA-ligand uptake after exposure to second-generation antiandrogens such as enzalutamide and abiraterone might disturb PSMA-targeted imaging for staging and response monitoring of patients undergoing treatment with antiandrogen-based drugs. On the other hand, second-generation antiandrogens are emerging as potential endoradio-/chemosensitizers. Therefore, the enhancement of the therapeutic efficiency of PSMA-targeted theranostic methods can be listed as a new capability of antiandrogens. In this manuscript, we will present what is currently known about the mechanism of increasing PSMA uptake following exposure to antiandrogens. In addition, we will discuss whether these above-mentioned antiandrogens could play the role of endoradio-/chemosensitizers in combination with the well-established PSMA-targeted methods for pre-targeting of prostate cancer.

Incidentally Detected Small Intestine Intussusception Caused by Primary Small Intestine Carcinoma on ¹⁸F-FDG PET/CT / 대한핵의학회잡지

Small intestine intussusception in adults is a rare condition mainly caused by primary or metastatic small intestine malignancy. Here, we present a 72-year-old male patient who was diagnosed with small intestine cancer that was presented as small intestine intussusception on hybrid 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). The patient was initially referred for an abnormality on a chest radiography and severe anemia. FDG PET/CT showed the lung lesion in the right upper lobe of lung as a high FDG uptake mass. Accidentally, FDG PET demonstrated another intense hypermetabolic intraluminal lesion in the small intestine accompanied with intussusception shown as a circumferential hypermetabolic wall. By pathologic examination, the patient was diagnosed as primary small intestine cancer with lung metastasis. This case highlights usefulness of hybrid FDG PET/CT to identify unexpected malignancy.

New Strategies for Combined Radioiodine Therapy in Refractory Thyroid Cancer / 대한갑상선학회지

The prognosis of differentiated thyroid cancer (DTC) is excellent, which is mainly due to the high therapeutic efficacy of radioactive iodine (RAI) therapy as well as indolent nature of thyroid cancer itself. Although most patients with DTC are well treated with RAI therapy, a certain number of patients have been suffered from refractoriness to RAI therapy. To overcome refractoriness, many alternative treatments have been investigated, and they could be classified based on the mechanisms of action; redifferentiation drug and molecular targeted drug. Not only redifferentiated drugs but also molecular targeted drugs could induce differentiation of thyroid cancer cells. Consequently, alternative treatments allowing tumor cells of RAI avidity followed by RAI therapy could utilize a synergistic effect of both therapies. Combined RAI therapy is expected to improve therapeutic effects and prognoses of RAI refractory thyroid cancers.

Clinical Outcome of Remnant Thyroid Ablation with Low Dose Radioiodine in Korean Patients with Low to Intermediate-risk Thyroid Cancer

Radioiodine activity required for remnant thyroid ablation is of great concern, to avoid unnecessary exposure to radiation and minimize adverse effects. We investigated clinical outcomes of remnant thyroid ablation with a low radioiodine activity in Korean patients with low to intermediate-risk thyroid cancer. For remnant thyroid ablation, 176 patients received radioiodine of 1.1 GBq, under a standard thyroid hormone withdrawal and a low iodine diet protocol. Serum levels of thyroid stimulating hormone stimulated thyroglobulin (off-Tg) and thyroglobulin-antibody (Tg-Ab), and a post-therapy whole body scan (RxWBS) were evaluated. Completion of remnant ablation was considered when there was no visible uptake on RxWBS and undetectable off-Tg (<1.0 ng/mL). Various factors including age, off-Tg, and histopathology were analyzed to predict ablation success rates. Of 176 patients, 68.8% (n = 121) who achieved successful remnant ablation were classified into Group A, and the remaining 55 were classified into Group B. Group A presented with significantly lower off-Tg at the first radioiodine administration (pre-ablative Tg) than those of Group B (1.2 +/- 2.3 ng/mL vs. 6.2 +/- 15.2 ng/mL, P = 0.027). Pre-ablative Tg was the only significant factor related with ablation success rates. Diagnostic performances of pre-ablative Tg < 10.0 ng/mL were sensitivity of 99.1%, specificity of 14.0%, positive predictive value of 71.1%, and negative predictive value of 87.5%, respectively. Single administration of low radioiodine activity could be sufficient for remnant thyroid ablation in patients with low to intermediate-risk thyroid cancer. Pre-ablative Tg with cutoff value of 10.0 ng/mL is a promising factor to predict successful remnant ablation.

Prediction of response by FDG PET early during concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

PURPOSE: To evaluate the predictive value of the early response of 18F-flurodeoxyglucose positron emission tomography (FDG PET) during concurrent chemoradiotherapy (CCRT) for locally advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: FDG PET was performed before and during CCRT for 13 NSCLC patients. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured and the changes were calculated. These early metabolic changes were compared with the standard tumor response by computed tomograms (CT) one month after CCRT. RESULTS: One month after the completion of CCRT, 9 patients had partial response (PR) of tumor and 4 patients had stable disease. The percent changes of SUVmax (%DeltaSUVmax) were larger in responder group than in non-responder group (55.7% +/- 15.6% vs. 23.1% +/- 19.0%, p = 0.01). The percent changes of SUVmean (%DeltaSUVmean) were also larger in responder group than in non-responder group (54.4% +/- 15.9% vs. 22.3% +/- 23.0%, p = 0.01). The percent changes of MTV (%DeltaMTV) or TLG (%DeltaTLG) had no correlation with the tumor response after treatment. All the 7 patients (100%) with %DeltaSUVmax > or = 50% had PR, but only 2 out of 6 patients (33%) with %DeltaSUVmax or = 50% had PR, but only 3 out of 7 patients (43%) with %DeltaSUVmean < 50% had PR after CCRT (p = 0.026). CONCLUSION: The degree of metabolic changes measured by PET-CT during CCRT was predictive for NSCLC tumor response after CCRT.

Pulmonary Artery Embolotherapy in a Patient with Type I Hepatopulmonary Syndrome after Liver Transplantation

Although liver transplantation (LT) is the only effective treatment option for hepatopulmonary syndrome (HPS), the post-LT morbidity and mortality have been high for patients with severe HPS. We performed post-LT embolotherapy in a 10-year-old boy who had severe type I HPS preoperatively, but he failed to recover early from his hypoxemic symptoms after an LT. Multiple embolizations were then successfully performed on the major branches that formed the abnormal vascular structures. After the embolotherapy, the patient had symptomatic improvement and he was discharged without complications.

Camurati-Engelmann's Disease on (99m)Tc-MDP Bone Scan / 핵의학분자영상

A 24 year-old female presented for a (99m)Tc-methylene diphosphonatae (MDP) whole body bone scan due to chronic pain in the bilateral lower extremities that has aggravated since 2002. She was diagnosed with Camurati-Engelmann disease (CED) based on the clinical and radiological findings in 2002, and she re-visited our institute to evaluate disease status at this time. CED is a rare autosomal dominant type of bone dysplasia characterized by progressive cortical thickening of long bones, and narrowing of medullary cavity, and thus presents with typical clinical symptoms and signs such as chronic pain in the extremities, muscle weakness, and waddling gait. On the (99m)Tc-MDP bone scan performed to evaluate disease status, intense increased uptake was seen in the skull, facial bones, bilateral scapulae, bilateral long bones, and bilateral pelvic bones, which clearly demonstrated the extent of CED involvement.

Diffuse Bone Marrow Uptake of 99mTc-MIBI in A Case of Intravascular Large B-cell Lymphoma / 핵의학분자영상

Intravascular large B-cell lymphoma (IVLBCL) is a subtype of diffuse large cell lymphoma, characterized by proliferation of lymphoid cells in the intravascular space of various organs without causing a mass effect. Although 18F-FDG PET is a powerful imaging tool in lymphoma, the usefulness of 18F-FDG PET in the assessment of IVLBCL is still controversial. 99mTc-MIBI, a tumor imaging radiopharmaceutical with a different mechanism from that of 18F-FDG, has been reported to be also effective in lymphoma. However, there is nearly no report on the efficacy of 99mTc-MIBI in the assessment of IVLBCL. We present one case of IVLBCL that showed 99mTc-MIBI accumulation in the involved bone marrow as an incidental finding, which was discrepant from that of 18F-FDG PET.

Evaluation of Multiple System Atrophy and Early Parkinson's Disease Using (123)I-FP-CIT SPECT / 핵의학분자영상

PURPOSE: We investigated quantification of dopaminergic transporter (DAT) and serotonergic transporter (SERT) on (123)I-FP-CIT SPECT for differentiating between multiple systemic atrophy (MSA) and idiopathic Parkinson's disease (IPD). MATERIALS AND METHODS: N-fluoropropyl-2beta-carbomethoxy-3beta-4-[(123)I]-iodophenylnortropane SPECT ((123)I-FP-CIT SPECT) was performed in 8 patients with MSA (mean age: 64.0+/-4.5yrs, m:f=6:2), 13 with early IPD (mean age: 65.5+/-5.3yrs, m:f=9:4), and 12 healthy controls (mean age: 63.3+/-5.7yrs, m:f=8:4). Standard regions of interests (ROIs) of striatum to evaluate DAT, and hypothalamus and midbrain for SERT were drawn on standard template images and applied to each image taken 4 hours after radiotracer injection. Striatal specific binding for DAT and hypothalamic and midbrain specific binding for SERT were calculated using region/reference ratio based on the transient equilibrium method. Group differences were tested using ANOVA with the postHoc analysis. RESULTS: DAT in the whole striatum and striatal subregions were significantly decreased in both patient groups with MSA and early IPD, compared with healthy control (p<0.05 in all). In early IPD, a significant increase in the uptake ratio in anterior and posterior putamen and a trend of increase in caudate to putamen ratio was observed. In MSA, the decrease of DAT was accompanied with no difference in the striatal uptake pattern compared with healthy controls. Regarding the brain regions where (123)I-FP-CIT binding was predominant by SERT, MSA patients showed a decrease in the binding of (123)I-FP-CIT in the pons compared with controls as well as early IPD patients (MSA: 0.22+/-0.1 healthy controls: 0.33+/-0.19, IPD: 0.29+/-0.19), however, it did not reach the statistical significance. CONCLUSION: In this study, the differential patterns in the reduction of DAT in the striatum and the reduction of pontine (123)I- FP-CIT binding predominant by SERT could be observed in MSA patients on (123)I- FP-CIT SPECT. We suggest that the quantification of SERT as well as DAT using (123)I- FP-CIT SPECT is helpful to differentiate parkinsonian disorders in early stage.

Defect of 18F-FDG Uptake Observed in Infarcted Myocardium Showing Reverse Redistribution on Rest / 24-Hour Delayed 201Tl Myocardial SPECT after Acute Myocardial Infarction / 핵의학분자영상

Reverse redistribution is frequently observed after revascularization in acute myocardial infarction, and usually regarded as a predictor of viable myocardium on stress/rest and 2- to 4-hour redistribution 201Tl SPECT. However, there is not enough report of reverse redistribution in case of 24-hour delayed SPECT, which is commonly used for viability assessment. In this report, a case of reverse redistribution on rest and 24-hour delayed 201Tl SPECT is reported with use of automatic segmental quantitative analysis. The myocardium of reverse redistribution was dysfunctional on gated SPECT, and diagnosed as non-viable on 18F-FDG PET.

Evaluation of Usefulness of Radio-iodine SPECT/CT in Differentiated Thyroid Cancer / 핵의학분자영상

PURPOSE: Localizing and differentiating a metastatic lesion of differentiated thyroid cancer (DTC) by using radio?iodine whole body scan could be difficult because a whole body scan (WBS) lacks anatomic information. This study was performed to evaluate the usefulness of radio-iodine SPECT/CT for differentiating equivocal lesions. MATERIALS AND METHODS: Among 253 patients with DTC who had undergone radio-iodine scan between February and July 2006, 26 patients were enrolled (M:F = 8:18, Age 50.7 +/- 12.5 years) in this study. The patients had abnormal uptakes in the WBSs that necessitated precise anatomical localization for differentiating between a metastatic lesion and a false-positive lesion. SPECT/CT was performed for the region with abnormal uptake in the WBS. WBS and SPECT/CT were evaluated visually. Metastases were diagnosed based on the results of the radio-iodine scan along with the results of other radiological examinations and serological tests. RESULTS: Based on the WBS images, 13 were suspected with cervical lymph node (LN) metastases in 16 patients with abnormal neck uptake, and in the 11 patients with abnormal extra-cervical uptakes, extra-cervical metastases were doubtful in all. After SPECT/CT was performed, the diagnostic results were altered for 16 patients (62%). SPECT/CT revealed that only 5 patients had cervical LN metastases, while 3 patients had extra-cervical (mediastinal) LN metastases. Overall, there was a 58% (15/26) change in diagnoses and plans for treatment due to SPECT/CT. Among 8 patients suspected with metastases on SPECT/CT, 6 patients underwent another radio-iodine therapy. In 96% (24/25) of the patients, the results of SPECT/CT corresponded with those of further radiological examinations and with other clinical information. CONCLUSION: Radio-iodine SPECT/CT images permitted the differentiation of abnormal radio-iodine uptake and improved anatomical interpretation in DTC.