Radiolabeled Liposomes for Nuclear Imaging Probes.

Quantitative nuclear imaging techniques are in high demand for various disease diagnostics and cancer theranostics. The non-invasive imaging modality requires radiotracing through the radioactive decay emission of the radionuclide. Current preclinical and clinical radiotracers, so-called nuclear imaging probes, are radioisotope-labeled small molecules. Liposomal radiotracers have been rapidly developing as novel nuclear imaging probes. The physicochemical properties and structural characteristics of liposomes have been elucidated to address their long circulation and stability as radiopharmaceuticals. Various radiolabeling methods for synthesizing radionuclides onto liposomes and synthesis strategies have been summarized to render them biocompatible and enable specific targeting. Through a variety of radionuclide labeling methods, radiolabeled liposomes for use as nuclear imaging probes can be obtained for in vivo biodistribution and specific targeting studies. The advantages of radiolabeled liposomes including their use as potential clinical nuclear imaging probes have been highlighted. This review is a comprehensive overview of all recently published liposomal SPECT and PET imaging probes.

Facing a disruptive threat: how can a nuclear medicine service be prepared for the coronavirus outbreak 2020?

PURPOSE: The aim of this short communication is to outline our experience in policies and processes of a nuclear medicine service during the COVID-19 outbreak in Singapore. METHODS: We describe the key considerations of policies and processes that have been implemented in our nuclear medicine service since the first case of COVID-19 was confirmed in Singapore General Hospital on 23 January 2020, up to the present time. RESULTS: Infection control, screening of patients and visitors, segregation of risk groups, segregation of staff and service continuity plans, communication and staff welfare, using electronic platforms for multi-disciplinary meetings and tele-reporting are discussed. CONCLUSION: Since our hospital received the first patient with COVID-19 in Singapore, our centre has managed 16 COVID-19 cases to date. There has not been any healthcare worker in our institution who has contracted COVID-19 through patient contact. We have highlighted for discussion some of the policies and processes to prepare a nuclear medicine service for the COVID-19 threat.

Subacute Thyroiditis-An Often Overlooked Sonographic Diagnosis: Report of 3 Cases.

The characteristic sonographic finding of subacute thyroiditis of a heterogeneous poorly defined hypoechoic area in the thyroid gland may mimic that of thyroid malignancy. This finding needs to be interpreted in the correct clinical context to avoid an unnecessary biopsy. We describe 3 patients who underwent thyroid biopsy on the basis of suspicious sonographic findings but who subsequently had a diagnosis of subacute thyroiditis.

SPECT/CT in musculoskeletal infections.

This article provides a brief overview of the current state of hybrid single-photon emission computed tomography/computer tomography (SPECT/CT) imaging in musculoskeletal infections. SPECT/CT imaging, compared with conventional planar study and SPECT alone, provides improved anatomic localization of infection and more accurate delineation of the extent of infection. This article emphasizes three clinical aspects where SPECT/CT is found to be most useful: differentiating between soft tissue and bone infections, assessing suspected infected sites with underlying structural bone alterations, and defining infective focus when complex anatomy is involved. The accurate assessment of site of infection is vital for selecting the most appropriate therapeutic strategy. Other advantages of SPECT/CT imaging such as reducing the inconvenience of combination planar studies, providing additional CT information, and increasing interobserver agreement are also discussed.

The Curious Case of the Missing Limb on FDG PET Imaging.

ABSTRACT: A 58-year-old woman with poorly controlled diabetes, peripheral vascular disease, and end-stage renal disease requiring hemodialysis was referred for 18 F-FDG PET/CT to evaluate for source of sepsis. She had history of prior left forefoot and right second toe amputation, as well as left lower-limb dry gangrene for which she declined surgical management. We present a case of a nonamputated lower limb demonstrating regions of absolute photopenia, consistent with dry gangrene.

Safety and Efficacy of 90Y Selective Internal Radiation Therapy Using Glass Microspheres in Hepatocellular Carcinoma: A Southeast Asian Single-Institution Initial Experience.

Our objective was to demonstrate primarily the safety and secondarily the efficacy of 90Y glass microspheres in selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC) in a local Southeast Asian hospital. Methods: Eleven consecutive patients with small, unresectable, nonmetastatic HCC and referred for locoregional therapy with SIRT with a curative intention were followed up for 6 mo after the procedure by way of interviews, blood tests, and anatomic scans. Results: Although 5 patients had deranged liver function tests after the procedure, in only 1 patient did this constitute a grade 1 toxicity (in alkaline phosphatase) by the Common Terminology Criteria for Adverse Events. Half the patients showed a reduction in serum α-fetoprotein measurements, and 6 of 11 patients demonstrated an objective response (complete or partial) on imaging. Conclusion: SIRT with 90Y glass microspheres is a safe and efficacious locoregional therapy for unresectable HCC. There are similar articles published in the West; however, the patient population there comprises far fewer Asians and the underlying cause for HCC is different from that in the Asian population. Despite these differences, SIRT is an equally effective and safe option for such patients.

"Seeing Is Believing": Additive Utility of 68Ga-PSMA-11 PET/CT in Prostate Cancer Diagnosis.

Widespread adoption of mpMRI has led to a decrease in the number of patients requiring prostate biopsies. 68Ga-PSMA-11 PET/CT has demonstrated added benefits in identifying csPCa. Integrating the use of these imaging techniques may hold promise for predicting the presence of csPCa without invasive biopsy. A retrospective analysis of 42 consecutive patients who underwent mpMRI, 68Ga-PSMA-11 PET/CT, prostatic biopsy, and radical prostatectomy (RP) was carried out. A lesion-based model (n = 122) using prostatectomy histopathology as reference standard was used to analyze the accuracy of 68Ga-PSMA-11 PET/CT, mpMRI alone, and both in combination to identify ISUP-grade group ≥ 2 lesions. 68Ga-PSMA-11 PET/CT demonstrated greater specificity and positive predictive value (PPV), with values of 73.3% (vs. 40.0%) and 90.1% (vs. 82.2%), while the mpMRI Prostate Imaging Reporting and Data System (PI-RADS) 4-5 had better sensitivity and negative predictive value (NPV): 90.2% (vs. 78.5%) and 57.1% (vs. 52.4%), respectively. When used in combination, the sensitivity, specificity, PPV, and NPV were 74.2%, 83.3%, 93.2%, and 51.0%, respectively. Subgroup analysis of PI-RADS 3, 4, and 5 lesions was carried out. For PI-RADS 3 lesions, 68Ga-PSMA-11 PET/CT demonstrated a NPV of 77.8%. For PI-RADS 4-5 lesions, 68Ga-PSMA-11 PET/CT achieved PPV values of 82.1% and 100%, respectively, with an NPV of 100% in PI-RADS 5 lesions. A combination of 68Ga-PSMA-11 PET/CT and mpMRI improved the radiological diagnosis of csPCa. This suggests that avoidance of prostate biopsy prior to RP may represent a valid option in a selected subgroup of high-risk patients with a high suspicion of csPCa on mpMRI and 68Ga-PSMA-11 PET/CT.

Semi-quantitative indices of 2-[18F]FDG PET/CT in assessing cardiovascular and non-cardiovascular manifestations of IgG4-related disease and treatment response.

BACKGROUND: IgG4-related disease (IgG4-RD) is a heterogeneous autoimmune disorder characterised by inflammatory lesions. Diagnostic imaging, such as 2-[18F]FDG PET/CT, is critical in evaluation of the disease, especially for potentially lethal cardiovascular manifestations. This retrospective study examines the usefulness of semi-quantitative parameters of 2-[18F]FDG PET/CT in monitoring IgG4-RD in patients with and without cardiovascular manifestations. METHODS: Patients diagnosed with IgG4-RD who underwent a 2-[18F]FDG PET/CT scan were identified and classified based on presence or absence of cardiovascular disease. Clinical and laboratory data were extracted and compared to three 2-[18F]FDG PET/CT semi-quantitative parameters: maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG). Tissue-to-background blood (TBR) values were also evaluated for cardiovascular manifestations. These data were also compared in patients before and after receiving immunosuppressive therapy. RESULTS: Forty-six patients identified were divided into an eight member subgroup of patients with cardiovascular manifestations, and a thirty-eight member subgroup of patients without. Patients with cardiovascular lesions were most frequently identified incidentally on imaging evaluation for other diseases (37.5%), with none presenting with chest pain or other cardiovascular symptoms. Ten patients with pre-treatment and post-treatment 2-[18F]FDG PET/CT scans demonstrated significant decreases in all semi-quantitative parameters, with no significant decrease in total IgG or ESR. The decrease in SUVmax, MTV, TLG following therapy was replicated in patients with and without cardiovascular manifestations. CONCLUSION: 2-[18F]FDG PET/CT is an important investigation to determine all sites of involvement in this multisystemic disease and to rule out life-threatening cardiovascular manifestations even in the absence of symptoms. Semi-quantitative parameters such as SUVmax, MTV, TLG, and TBR are useful in assessing treatment response in patients. There are no serological substitutes that can quantify the extent of disease involvement like 2-[18F]FDG PET/CT.

Outcomes and prognostic predictors of Lu-177 PSMA radioligand therapy in metastatic castration-resistant prostate cancer (Asian Population Study).

AIM: Lutetium-177 (Lu-177) prostate-specific membrane antigen radioligand therapy (PSMA-RLT) is a promising therapy for metastatic castration-resistant prostate cancer (mCRPC), but there is limited data of its efficacy and safety in Asian population. We aim to explore the clinical outcomes of Lu-177 PSMA-RLT in this population. METHODS: We evaluated 84 patients with progressive mCRPC receiving Lu-177 PSMA-RLT between 9 May 2018 and 21 February 2022. Lu-177-PSMA-I&T was administered at 6-8-week intervals. Primary end point was overall survival (OS), and secondary end points included prostate-specific antigen (PSA) progression-free survival (PFS), PSA response rate, clinical response, toxicity assessment, and prognostic indicators. RESULTS: The median OS and PSA PFS were 12.2 and 5.2 months, respectively. PSA decline of ≥50% was observed in 51.8% of patients. Patients achieving PSA response had longer median OS (15.0 vs. 9.5 months, p = .03) and PSA PFS (6.5 vs. 2.9 months, p < .001). Pain score improvement was seen in 19 out of 34 patients. A hematotoxicity of ≥grade 3 was observed in 13 out of 78 patients. Multivariable analyses showed that PSA velocity, alkaline phosphatase, hemoglobin (Hb), and the number of treatment cycles were independent prognostic indicators for OS. The retrospective design was the main limitation of the study. CONCLUSIONS: Our study demonstrated a similar safety and efficacy of Lu-177 PSMA-RLT in Asian mCRPC patients compared to the existing literature. A PSA decline ≥50% was associated with longer OS and PSA PFS. Several prognostic indicators for patient outcomes were also identified.

Safety and efficacy of peptide receptor radionuclide therapy in patients with advanced pheochromocytoma and paraganglioma: A single-institution experience and review of the literature.

INTRODUCTION: Despite advances in diagnosis and management, patients with advanced pheochromocytomas and paragangliomas (PPGL) face limited treatment options. This study aims to evaluate the safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced PPGL, based on a single-institution experience and provide a comprehensive review of the literature. METHODS: A retrospective analysis was conducted on patients with advanced pheochromocytoma and paraganglioma who received PRRT at a single institution from April 2012 to March 2022. Clinical characteristics, treatment response, adverse events, and survival outcomes were assessed. A systematic literature review was also performed. RESULTS: A total of 15 patients with advanced PPGL were included, the majority of whom had both metastatic and functional disease. Most patients received four infusions of 177Lu-DOTATATE (73%). The median therapeutic 177Lu-DOTATATE radioactivity for each infusion was 7.4 GBq. Only one patient was treated with one infusion of 90Y-DOTATATE (4.2 GBq) in addition to three infusions of Lu-177 DOTATATE. Overall, PRRT suggests a promising efficacy with disease control rate of 63.6% by RECIST v1.1. The median overall survival (OS) was not reached and the median progression free survival (PFS) was 25.9 months. In terms of safety, PRRT was well tolerated. Review of the literature revealed consistent findings, supporting the efficacy and safety of PRRT in PPGL. CONCLUSION: This study suggests that PRRT is a safe and effective therapeutic option for patients with PPGL. Our findings align with the existing literature, providing additional evidence to support the use of PRRT in this challenging patient population.

Optimization of Bayesian penalized likelihood reconstruction for 68 Ga-prostate-specific membrane antigen-11 PET/computed tomography.

OBJECTIVE: The objective of this study is to determine the optimal ß value for clinical use in digital 68 Ga-prostate-specific membrane antigen (PSMA-11) PET/computed tomography (CT) imaging. METHODS: 68 Ga PSMA PET/CT of 21 patients with prostate cancer were reconstructed using block-sequential regularized expectation maximization ( ß value of 400-1600) and ordered subsets expectation maximization. Nine independent blinded readers evaluated each reconstruction for overall image quality, noise level and lesion detectability. Maximum standardized uptake value (SUVmax) of the most intense lesion, liver SUVmean and liver SUV SD were recorded. Lesions were then subdivided according to uptake and size; the SUVmax of these lesions were analyzed. RESULTS: There is a statistically significant correlation between improvement in image quality and ß value, with the best being ß 1400. This trend was also seen in image noise ( P  < 0.001), with the least image noise reported with ß 1400. Lesion detectability was not significantly different between the different ß values ( P  =  0.6452). There was no statistically significant difference in SUVmax of the most intense lesion ( P  = 0.9966) and SUVmean of liver background between the different ß values ( P  = 0.9999); however, the SUV SD of the liver background showed a clear trend, with the lowest with ß 1400 ( P  = 0.0008). There was a decreasing trend observed in SUVmax when ß values increased from 800 to 1400 for all four subgroups, and this decrease was greatest in small and low uptake lesions. CONCLUSION: Bayesian penalized likelihood reconstruction algorithms improve image quality without affecting lesion detectability. A ß value of 1400 is optimal.

18F-FMISO PET-guided dose escalation with multifield optimization intensity-modulated proton therapy in nasopharyngeal carcinoma.

PURPOSE: The purpose of this study was to evaluate the radiotherapy planning feasibility of dose escalation with intensity-modulated proton therapy (IMPT) to hypoxic tumor regions identified on 18F-Fluoromisonidazole (FMISO) positron emission tomography and computed tomography (PET-CT) in NPC. MATERIALS AND METHODS: Nine patients with stages T3-4N0-3M0 NPC underwent 18F-FMISO PET-CT before and during week 3 of radiotherapy. The hypoxic volume (GTVhypo) is automatically generated by applying a subthresholding algorithm within the gross tumor volume (GTV) with a tumor to muscle standardized uptake value (SUV) ratio of 1.3 on the 18F-FMISO PET-CT scan. Two proton plans were generated for each patient, a standard plan to 70 Gy and dose escalation plan with upfront boost followed by standard 70GyE plan. The stereotactic boost was planned with single-field uniform dose optimization using two fields to deliver 10 GyE in two fractions to GTVhypo. The standard plan was generated with IMPT with robust optimization to deliver 70GyE, 60GyE in 33 fractions using simultaneous integrated boost technique. A plan sum was generated for assessment. RESULTS: Eight of nine patients showed tumor hypoxia on the baseline 18F-FMISO PET-CT scan. The mean hypoxic tumor volume was 3.9 cm3 (range .9-11.9cm3 ). The average SUVmax of the hypoxic volume was 2.2 (range 1.44-2.98). All the dose-volume parameters met the planning objectives for target coverage. Dose escalation was not feasible in three of eight patients as the D0.03cc of temporal lobe was greater than 75GyE. CONCLUSIONS: The utility of boost to the hypoxic volume before standard course of radiotherapy with IMPT is dosimetrically feasible in selected patients. Clinical trials are warranted to determine the clinical outcomes of this approach.

18F-FDG PET/CT Manifestations of IgG4-related Disease.

Immunoglobulin G4-related disease (IgG4-RD) was not recognised as a systemic condition until 2003, when extra pancreatic manifestations were identified in patients with autoimmune pancreatitis. Since then, IgG4-RD has been described to involve virtually every organ system. It is highly responsive to immunosuppressants but can have detrimental effects if left untreated. Early recognition of the disease is, therefore, critical. The diagnosis of IgG4-RD is frequently challenging owing to its non-specific clinical manifestations, indolent nature and broad differential diagnoses. Although histopathological examination remains the cornerstone of diagnosis, imaging plays an important role in establishing extent of disease and identifying areas suitable for biopsy. 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been demonstrated to be useful in assessing organ involvement, guiding biopsy and monitoring disease response. The 18F-FDG PET/CT scan is highly sensitive and able to evaluate multiorgan involvement in a single examination, a key advantage over conventional imaging modalities. A potential pitfall is its low specificity. As such, detailed knowledge of the imaging findings in IgG4-related disease is required to avoid misdiagnosis. This pictorial review aims to depict the diverse spectrum of imaging findings of IgG4-RD and the key imaging features to distinguish it from other important differential diagnoses.

Clinical outcomes of 177lutetium-prostate-specific membrane antigen therapy in advanced prostate cancer-a prospective pilot study in an Asian population.

OBJECTIVE: Metastatic castration-resistant prostate cancers are aggressive tumors with poor prognosis. Prostate-specific membrane antigen-targeted radionuclide therapy is a potential treatment for these patients. Here, we report our initial experience in Singapore. METHODS: Twenty men (median age 70) with progressive disease were prospectively recruited. Prostate-specific membrane antigen and fluorodeoxyglucose-PET/computed tomography were performed to confirm high prostate-specific membrane antigen-expression. Up to four cycles of lutetium-prostate-specific membrane antigen-I&T at 6-8 weekly intervals were administered. Patients were restaged 3 months following treatment. Primary endpoints were prostate-specific antigen decline ≥50% and treatment-related toxicity. Additional endpoints included radiological and clinical response as well as progression-free survival and overall survival from first cycle. RESULTS: Sixty-seven cycles were administered (median 4 cycles per patient, mean 6.5 GBq per cycle). Sixty five percent had ≥1 line of prior chemotherapy, 90% abiraterone, enzalutamide or both, and 30% radium-223 radionuclide therapy. All had bone metastases and 35% had visceral metastases. Prostate-specific antigen decline ≥50% was achieved in 50%. Grade 3-4 hematotoxicity was seen in up to 15%. Grade 3-4 non-hematotoxicity was not observed. Eleven patients had restaging scans 3 months post-treatment (5 = partial response, 6 = progressive disease). Fifty-seven percent (4/7) with bone pain had pain improvement. Median progression-free survival was 5.9 months and median overall survival 13.1 months. Patients with prostate-specific antigen decline ≥50% had longer progression-free survival and overall survival. CONCLUSION: Lutetium-prostate-specific membrane antigen-I&T therapy is effective with tolerable side effects in our local setting. Prostate-specific antigen decline ≥50% is associated with longer progression-free survival and overall survival.

Current Status and Growth of Nuclear Theranostics in Singapore.

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of 'personalised' medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore. We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy. We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.

Cardiac structural abnormalities associated with IgG4-related coronary periarteritis and inflammation revealed by multimodality imaging.

A man presented with shortness of breath, and a globular heart was seen on a chest radiograph. An echocardiogram showed masses at the atrioventricular grooves. Computed tomography (CT) coronary angiography and fluorine-18 ((18)F) fluorodeoxyglucose positron emission tomography (FDG-PET)/CT confirmed coronary aneurysms with hypermetabolic perivascular masses at the coronary arteries and right internal iliac artery. Histologic features were highly suspicious for IgG4-related disease (IgG4-RD). IgG4-RD is a recently recognized fibroinflammatory condition, and FDG-PET/CT can provide information about the disease pattern, which may suggest IgG4-RD, as well as the optimal biopsy site.

Promising role of [18F] fluorocholine PET/CT vs [18F] fluorodeoxyglucose PET/CT in primary brain tumors-early experience.

Primary brain tumors (PBT), in particular gliomas, are among the most difficult neoplasms to treat, necessitating good quality imaging to guide clinicians at many junctures. Current imaging modalities, including [18F] fluorodeoxyglucose (FDG) PET/CT, MRI and MR spectroscopy (MRS), have various limitations, particularly with regard to differentiating tumor from radiation induced necrosis (RIN) and from normal cerebral metabolic uptake. [18F] fluorocholine (FCH) is an analog of choline with potentially optimal imaging characteristics, as pharmacokinetic studies with FCH conducted in patients showed minimal FCH uptake by normal brain parenchyma, whereas high-grade tumors are known to have increased choline uptake. We present two cases of our early experience with FCH PET/CT for patients with PBT and discuss the potential use and comparative limitations of this imaging modality.

Pancreatic metastasis detected by F-18 FDG PET/CT in a patient with breast cancer.

Pancreatic involvement by metastasis from other primaries is rare and accounts for approximately 2% to 4% of pancreatic tumors. In this article, we describe FDG-avid pancreatic involvement in a patient with diagnosis of breast cancer. We conclude that FDG PET can be a convenient noninvasive method of early detection of recurrence and in monitoring metastatic disease during follow-up in such patients. A positive FDG PET warrants histopathologic correlation for appropriate treatment.

Colour Doppler ultrasonography replacing surgical exploration for acute scrotum: myth or reality?

BACKGROUND: Traditionally, every patient with an acute scrotum needed surgical exploration for definitive exclusion of testicular torsion. OBJECTIVE: In this study, we aimed to evaluate the improved accuracy in clinical diagnosis with colour Doppler Ultrasonography (US) added to normal clinical assessment. MATERIALS AND METHODS: We retrospectively reviewed 626 patients, who presented with acute scrotal pain between January 1998 and June 2004. Following history and physical examination, the patients either proceeded directly to surgery or underwent US examination. If clinical suspicion of testicular torsion persisted after US, the patients would still undergo scrotal exploration. RESULTS: Of the 294 patients who had routine scrotal exploration without preliminary US, only 23 (7.8%) were found to have testicular torsion. Amongst the 332 cases that had initial US, 9 (2.7%) patients revealed testicular torsion that was confirmed at subsequent surgery. The remaining 323 patients had initial negative US, but 29 were explored eventually on clinical indications. Of these, 4 (1.2% of 323) cases were diagnosed intra-operatively as testicular torsion. None of the remaining 294 patients who were managed conservatively proved to have testicular torsion after a minimum follow-up of 2 weeks. For testicular torsion, US yielded a sensitivity of 69.2% (95% confidence interval =38.9-89.5), specificity of 100% (95% CI=98.5-100), positive predictive value of 100% and negative predictive value of 97.5%. CONCLUSIONS: US has proven to decrease the number of emergency scrotal explorations, length of hospital stay and hence reduce the cost of management of acute scrotum.