Favourable outcomes of (177)Lu-octreotate peptide receptor chemoradionuclide therapy in patients with FDG-avid neuroendocrine tumours.

PURPOSE: Increased glycolytic activity on FDG PET/CT defines a subgroup of patients with metastatic gastroenteropancreatic neuroendocrine tumour (NET) with a poor prognosis. A limited range of systemic treatment options exist for more aggressive NET. The role of peptide receptor chemoradionuclide therapy (PRCRT) in such patients is, however, unclear. This retrospective study assessed the outcomes of patients with FDG-avid NET treated with PRCRT. METHODS: Clinical, biochemical and imaging response was assessed after completion of induction treatment of PRCRT with 5-fluorouracil in 52 patients selected for treatment on the basis of somatostatin-receptor imaging without spatially discordant FDG-avid disease. Of the cohort, 67% had received prior chemotherapy. Overall survival (OS) and progression-free survival (PFS) were also analysed. RESULTS: PRCRT was well tolerated with negligible grade 3/4 toxicities. After a median follow-up period of 36 months, the median OS was not achieved with a median PFS of 48 months. At 3 months after completion of PRCRT 2% of patients showed a complete anatomical response, 28% a partial response, 68% stable disease, and only 2% progression. On FDG PET/CT, 27% achieved a complete metabolic response during the follow-up period. A biochemical response (>25% fall in chromogranin-A levels) was seen in 45%. CONCLUSION: PRCRT is an effective treatment in patients with FDG-avid NET, even in patients who have failed conventional therapies. Given apparently higher response rates than with alternative therapeutic options and low toxicity, further research is needed to establish whether PRCRT should be used as a first-line treatment modality in this patient population.

Role of N-13 ammonia PET/CT in diagnosing pancreatic necrosis in patients with acute pancreatitis as compared to contrast enhanced CT--results of a pilot study.

BACKGROUND: Contrast enhanced computerized tomography (CECT) is used to determine severity of acute pancreatitis based upon the presence and extent of necrosis. However limitations do exist precluding its applicability in renal failure. Positron emission tomography (PET) imaging for cardiac perfusion shows good uptake of N-13 ammonia ((13)NH3) metabolites in pancreas owing to high perfusion. AIM: To evaluate the role of (13)NH3 PET/CT in acute pancreatitis and compare it with CECT in diagnosing and quantifying pancreatic necrosis. MATERIAL AND METHODS: Patients presenting within 1 week of acute pancreatitis were studied. Static PET images were acquired after intravenous injection of 370-740 MBq of (13)NH3. (13)NH3 PET/CT was followed by CECT in the absence of renal impairment. Maximum standard-uptake-value (SUVmax) of pancreas (P) and liver (L) were taken and their ratio (P/L) was estimated to determine perfusion. Areas within pancreas with no tracer uptake were considered necrotic. These patients were managed as per institutional protocol. Patients undergoing (13)NH3 PET/CT for coronary artery disease were used as controls. RESULTS: 29 patients (72% males) were studied of whom 6 had elevated serum creatinine. (13)NH3 PET/CT was done in all patients along with 9 controls while CECT was carried out after PET/CT in 23 patients. Median levels of SUVmax (P/L) in the controls, uninvolved pancreas and necrotic areas were 1.0 (0.86-1.03), 0.66 (0.50-0.92) and 0.12 (0.07-0.21) respectively (p < 0.001). Necrosis estimation was similar in 22/23 patients without renal failure while in one patient only (13)NH3 PET/CT picked up necrosis (<30%). 5/6 patients with renal failure had necrosis on (13)NH(3) PET/CT which was confirmed on surgery or subsequent CECT after improvement of renal failure. CONCLUSION: This pilot study is the first in literature to diagnose necrosis in patients with acute pancreatitis using (13)NH3 PET/CT. With minimal additional radiation burden, it is possible to estimate the absolute tissue perfusion as well. With no adverse renal side effects, this can be an alternative to CECT in patients with renal failure giving similar information. It has good agreement with CECT with a good interobserver acceptability.

Can 3'-deoxy-3'-(18)F-fluorothymidine or 2'-deoxy-2'-(18)F-fluoro-d-glucose PET/CT better assess response after 3-weeks treatment by epidermal growth factor receptor kinase inhibitor, in non-small lung cancer patients? Preliminary results.

The objectives of this study was to study the diagnostic efficacy of 3'-deoxy-3'-fluorine-18-fluorothymidine ((18)F-FLT) and of 2'-deoxy-2'-(18)F-fluoro-d-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) for response evaluation following three weeks treatment by epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in non small cell lung cancer (NSCLC) patients. Fifteen patients of advanced stage (IIIB-IV) NSCLC planned for oral 1st or 2nd/3rd line EGFR-TKI treatment were enrolled in the study. Baseline, prior to treatment, and follow-up after three weeks, (18)F-FLT and (18)F-FDG PET/CT imaging was performed in all patients. The standard uptake lean body mass (SULpeak) and total lesion glycolysis (TLG) values of the hottest lesions were calculated in all patients using semi-quantitative analysis. Statistical analysis on PET semi-quantitative data was used to evaluate the overall survival (OS) and progression free survival (PFS). The patients were either classified as responders or non-responders or at a steady state according to the PET response criteria in solid tumors (PERCIST). The receiver operating characteristic curve (ROC) analysis was done on the (18)F-FDG PET/CT clinical responders, to derive the cut-off values on the corresponding data sets between responders and non responders. Results showed that in responders (18)F-FDG SULpeak values better predicted OS and PFS values when compared to (18)F-FLT SULpeak values and also were a better predictor of OS as compared to the TLG values. In responders, the ROC analysis carried out on (18)F-FLT PET/CT imaging data in responders indicated a decrease of ≥22% in SULpeak and a decrease of ≥0.7 in absolute values. Three (3/15) patients developed resistance to EGFR-TKI treatment at 3 months of follow-up. In conclusion, in both responders and in non responders, patients with NSCLC treated for 3 weeks by EGFR-TKI, both OS and PFS were better predicted by (18)F -FDG SULpeak than by (18)F -FLT SULpeak. Although, the difference was only borderline, yet, (18)F -FDG SULpeak was a better predictor of OS compared to TLG values. However, to validate these findings, studies need to be carried in a larger number of patients.

Clinical Positron Emission Tomography/Computed Tomography: Quarter-Century Transformation of Prostate Cancer Molecular Imaging.

Although positron emission tomography/computed tomography (PET/CT) underwent rapid growth during the last quarter-century, becoming a new standard-of-care for imaging most cancer types, CT and bone scan remained the gold standard for patients with prostate cancer. This occurred as 2-fluorine-18-fluoro-2-deoxy-d-glucose was perceived to have a limited role owing to low sensitivity in many patients. A resurgence of interest occurred with the use of fluorine-18-sodium-fluoride PET/CT as a replacement for bone scintigraphy, and then choline, fluciclovine, and dihydrotestosterone (DHT) PET/CT as prostate "specific" radiotracers. The last decade, however, has seen a true revolution with the meteoric rise of prostate-specific membrane antigen PET/CT.

Role of neoadjuvant peptide receptor radionuclide therapy in unresectable and metastatic gastro-entero-pancreatic neuroendocrine neoplasms: A scoping review.

Peptide receptor radionuclide therapy (PRRT) is an established therapy for metastatic neuroendocrine neoplasms (NEN). The role of PRRT as a neoadjuvant treatment prior to surgery or other local therapies is uncertain. This scoping review aimed to define the landscape of evidence available detailing the utility of PRRT in the neo-adjuvant setting, including the clinical contexts, efficacy, and levels of evidence. A comprehensive literature search of PUBMED, SCOPUS, and EMBASE through to December 2022 was performed to identify reports of PRRT use as neoadjuvant therapy prior to local therapies. Observational studies and clinical trials were included. A total of 369 records were identified by the initial search, and 17 were included in the final analysis, comprising 179 patients treated with neoadjuvant PRRT. Publications included case reports, retrospective cohort series and a phase 2 trial. Definitions of unresectable disease were variable. Radioisotopes used included 177Lu (n = 142) and 90Y (n = 36), used separately (n = 178) or in combination (n = 1). A combination of PRRT with chemotherapy was also explored (n = 2). Toxicity data was reported in 11/17 studies. Survival analysis was reported in 3/17 studies. Surgical resection following PRRT was reported for both the primary tumor (n = 71) and metastases (n = 12). Resection rates could not be calculated as not all publications reported whether resection was completed. Published literature exploring the use of PRRT in the neoadjuvant setting is mostly limited to case reports and retrospective cohort studies. From these limited data there is reported to be a role of PRRT in neoadjuvant setting in the literature. However, the low quality of evidence precludes any definite conclusion on the grade of disease, site of primary, isotope used or use of concomitant chemotherapy that can benefit from this application. Further prospective studies will require collaboration between multiple centers to gain sufficient high-quality evidence.

Rapid blood clearance and lack of long-term renal toxicity of 177Lu-DOTATATE enables shortening of renoprotective amino acid infusion.

PURPOSE: The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion. METHODS: The whole-blood clearance of (177)Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion. RESULTS: LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline; 95 % CI -6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion. CONCLUSION: The greatest renal exposure to circulating radiopeptide occurs in the first 1 - 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation.

High FDG activity in focal fat necrosis: a pitfall in interpretation of posttreatment PET/CT in patients with non-Hodgkin lymphoma.

PURPOSE: PET/CT has a major role in lymphoma imaging, but glycolytic activity in inflammatory processes can reduce specificity. In this study we evaluated restaging PET/CT findings in patients with non-Hodgkin lymphoma (NHL) and fat necrosis. METHODS: We identified 16 patients from 8,819 restaging FDG PET/CT scans with suspicion of or biopsy-proven fat necrosis on PET/CT. RESULTS: All patients had NHL and demonstrated focal FDG-avid nodular change on CT with density higher than that of fat but lower than that of soft tissue. Histological confirmation was obtained in eight patients, with high GLUT-1 staining between necrotic tissue and organizing fat necrosis evident. Uptake resolved in four patients, and surveillance was continuing in four without relapse. CONCLUSION: Although rare, identification of fat necrosis in patients with a solitary FDG-avid nodule after therapy is important and may lead to the avoidance of unnecessary interventions or treatment. Specific features on CT aid identification, whilst follow-up imaging can be helpful as the metabolic abnormality regresses with time.

Correlation of current myocardial perfusion imaging and previous coronary angiography to avert the need for repeat intervention - A case report.

INTRODUCTION: Evaluation of chest pain in an individual with prior coronary artery bypass graft (CABG) procedures can be complex. Stress myocardial perfusion imaging (MPI) demonstrates reasonable sensitivity for detection of ischemia following bypass grafting [1] but often requires multi-modality imaging correlation for knowledge of graft anatomy. CASE AND OUTCOME: We describe the findings of a reversible perfusion defect on myocardial perfusion scintigraphy in a person post-CABG. This was interpreted in combination with findings of coronary angiography, thereby identifying ischemia in a native un-grafted vessel territory and influencing management strategy. DISCUSSION: Myocardial perfusion scintigraphy is a sensitive technique for evaluation of inducible ischemia. It provides information on the extent and severity of ischemia. Integrating the knowledge of changes on coronary angiography with MPI provides a comprehensive picture that can guide management decisions, as in our case. CONCLUSION: Correlation of structural and functional imaging findings may be extremely helpful for management of patients with myocardial ischemia post-CABG.

Safety of Lutetium-177 prostate-specific membrane antigen-617 (PSMA-617) radioligand therapy in the setting of severe renal impairment: a case report and literature review.

Reported here is a case of rapidly progressive metastatic castration-resistant prostate cancer treated with [177Lu]Lu-PSMA-617 in the setting of severe renal impairment and impending ureteric obstruction. PSMA is expressed on renal tubular cells, raising the possibility of radiation-induced nephrotoxicity, and this level of renal impairment would typically exclude the patient from [177Lu]Lu-PSMA-617 therapy. Multidisciplinary input, individualized dosimetry, and patient-specific dose reduction were used to ensure the cumulative dose to the kidneys remained within acceptable limits. He was initially planned for treatment with six cycles of [177Lu]Lu-PSMA-617. However, he had an excellent response to therapy following four cycles of treatment and the last two cycles were omitted. He has been followed for 1-year posttherapy without evidence of disease recurrence. No acute or chronic nephrotoxicity was observed. This case report highlights the utility of [177Lu]Lu-PSMA-617 therapy in severe renal impairment and provides evidence of relative safety in patients who would otherwise not be considered candidates for therapy.

This report presents a case of a man with aggressive metastatic prostate cancer who received [¹⁷⁷Lu]Lu-PSMA-617 therapy, despite having severely reduced kidney function and worsening ureter obstruction. This treatment could have potential side effects on kidney function, but the medical team used a personalized approach to reduce patient risk. The man was initially planned to have six cycles of therapy, but his excellent response to treatment after four cycles meant the last two cycles were not given. The man has been followed for 1 year after treatment and has not experienced any worsening kidney function. This case shows the safe and effective use of [¹⁷⁷Lu]Lu-PSMA-617 therapy in a patient with severely reduced kidney function who would not normally qualify for this treatment.

Comparison of nitrate augmented Tc-99m tetrofosmin gated SPECT imaging with FDG PET imaging for the assessment of myocardial viability in patients with severe left ventricular dysfunction.

BACKGROUND: Of various nuclear medicine techniques, F-18/flourodeoxyglucose (FDG) positron emission tomography (PET) is considered as the best modality for the assessment of viable myocardium (VM). In this study, we compared the diagnostic accuracy of nitrate augmented Tc-99m tetrofosmin gated G-single-photon emission computed tomography (SPECT) with FDG PET. METHODS: 54 consecutive cases of angiographically proven CAD with severe LV dysfunction were enrolled in the study. The patients underwent Tc-99m tetrofosmin G-SPECT and FDG PET as per the standard protocols and were compared. RESULTS: SPECT data analysis indicated functional abnormalities in 661/918 myocardial segments. F-18 FDG PET revealed VM in 496/661 segments. The diagnostic accuracy of baseline NAC, postnitrate NAC, baseline AC, and postnitrate AC Tc-99m tetrofosmin SPECT was 84%, 87%, 90%, and 94%, respectively. κ values for NAC baseline, NAC postnitrate, AC baseline, and AC postnitrate Tc-99m tetrofosmin G-SPECT were 0.65, 0.70, 0.77, and 0.85, respectively. Attenuation correction revealed viability additionally in 46 segments which were non-viable on NAC postnitrate study (P < .001). Nitrate augmentation showed viability additionally in 25 segments which were non-viable on AC baseline scan (P = .004). On patient-based analysis FDG PET changes the management only in 13% (7/54) of patients. CONCLUSIONS: Nitrate augmented AC Tc-99m tetrofosmin G-SPECT shows excellent (κ = .85) agreement with FDG PET. FDG PET changes management only in 13% of the patients. Tc-99m tetrofosmin G-SPECT being more widely available and cheaper imaging modality can be reliably used to detect VM where FDG PET is not available.

Ventricular ejection fraction in patients with dilated cardiomyopathy calculated by gated blood pool SPET processing software: correlation with multigated acquisition and first pass radionuclide ventriculography.

This study was performed to find out the left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) in patients with dilated cardiomyopathy (DCM) by using commercially available automated gated blood pool scintigraphy (GBPS) processing software and to correlate it with first pass radionuclide ventriculography (FPRNV) and planar multigated acquisition (MUGA). However, till date, no literature exists studying the application of GBPS and planar radionuclide ventriculography techniques in the setting of patients with DCM as a single cohort. Forty-one patients having DCM were prospectively included in the study. First pass RNV and MUGA were performed at rest after in-vivo labeling of red blood cells in all patients. Immediately after obtaining the planar views, GBPS was performed and LVEF and RVEF were calculated. Our results showed that the %LVEF values (mean±SD) calculated by MUGA, GBPS and echo cardiography were 31±11, 34±12 and 32±11, respectively. The % RVEF values (mean±SD) calculated by FPRNV and GBPS were 46±14 and 43±17, respectively. The LVEF values calculated by MUGA, GBPS and echcardiography showed very good correlation r=0.924 and r=0.844, respectively and for both P <0.0001. Bland-Altman plot showed overestimation for LVEF (and a tendency for overestimation of RVEF) values calculated by GBPS compared to MUGA. Values of RVEF calculated by GBPS and FPRNV also showed good correlation (r=0.88; P< 0.0001). In conclusion, the automated GBPS for LVEF and RVEF calculation using GBPS SPET can be routinely applied in DCM patients. Given the practical difficulties with FPRNV like good bolus administration, quantitative blood pool SPET (QBPS) can be used to calculate RVEF. Similarly MUGA and GBPS can be used to calculate LVEF.

A (99m)Tc-DTPA ventilation study in monitoring the effect of budesonide in asthmatic children.

This study was performed to identify the role of technetium-99m diethylene triamine penta-acetic acid ((99m)Tc DTPA) aerosol ventilation scintigraphy in the initial assessment and follow-up of children with bronchial asthma. In this prospective study conducted over a period of 2 years, 45 children (35M, 10F) aged 6-12 yrs (8.4 ± 2.2 years) with newly diagnosed moderate persistent bronchial asthma were included. Peak expiratory low (PEF) was measured and asthma symptom scores were calculated. Ventilation scintigraphy was performed after inhalation of (99m)Tc DTPA aerosol. The studies were repeated after 4 weeks of treatment with 400mcg budesonide daily. Pre and post treatment ventilation patterns were described, semiquantified and compared. Three patterns of ventilation were observed: a) homogenous (19/45), b) central airway deposition (21/45) and c) inhomogenous (5/45) with corresponding central: peripheral counts per pixel ratio of 1.265, 1.865 and 1.324 respectively. Ventilation pattern showed improvement (more counts in the periphery) in 22/45 children. Sixteen of 45 patients showed homogenous ventilation in both baseline and follow-up studies; abnormal central deposition was seen in both studies in 2/45. Five out of 45 children (3 with initial homogenous and 2 with initial inhomogenous patterns showed worsening on the follow-up scan after 4 weeks. In conclusion, semi-quantitave ventilation scintigraphy with (99m)Tc DTPA aerosol in asthmatic children repeated after 4 weeks treatment with budesonide showed better correlation with clinical symptom scores than PEF rates in monitoring response to treatment.

The role of (18)F-FDG PET/CT in initial staging of patients with locally advanced breast carcinoma with an emphasis on M staging.

Locally advanced breast cancer (LABC) is a distinct entity in breast carcinoma with high incidence of distant metastases (M). However, there is scarce data in the literature addressing the role of fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography ((18)F-FDG PET/CT) in LABC. This study was performed to assess the sensitivity of (18)F-FDG PET/CT in confirming known lymph nodal and M and in identifying new ones in LABC. We performed a retrospective analysis of data of 16 patients with LABC who underwent histopathology, for the diagnosis of LABC and clinical examination, chest X-rays, ultrasound of the abdomen and whole body bone scans. Findings for M obtained by all the above examinations were compared to the (18)F-FDG PET/CT findings that followed. Lymph nodal and distant metastases detected by all other examinations were detected by (18)F-FDG PET/CT in all patients, except subcentimetric metastases in 2 patients in the axilla that were detected in another examination later. Additionally, (18)F-FDG PET/CT identified unknown ipsilateral, supraclavicular, internal mammary metastases and upstaged disease in 3 patients and additional distant metastases were noted in 3/16 patients. In conclusion, our study suggests that more extra axillary lymph nodal and distant metastases can be identified by (18)F-FDG PET/CT as compared to a group of clinical, X-rays, ultrasound and bone scan examinations together.

(18)F-FDG PET/CT in bilateral primary adrenal T-cell lymphoma.

Primary adrenal lymphoma is extremely rare. We report a young patient who presented with non- specific symptoms of fever and abdominal pain. Conventional imaging modalities demonstrated bilateral bulky adrenal masses, and whole-body fluorine-18-fluorodesoxyglucose ((18)F-FDG) positron emission tomography/computed tomography showed intense (18)F-FDG-avid bilateral adrenal masses with no evidence of extra-adrenal spread. A pathological diagnosis of non-Hodgkin lymphoma of peripheral T-cell type was made. The present case indicates that primary adrenal lymphoma should be included in the differential diagnosis of bilateral adrenal masses.

Meningeal Relapse of Neuroblastoma-Utility of 68Ga-DOTATOC PET/CT for Detection.

ABSTRACT: In treatment of metastatic neuroblastoma, the central nervous system seems to act as a sanctuary leading to often unexpected relapse of disease. We present a case of neuroblastoma treated with chemotherapy and autologous stem cell transplantation only to relapse in central nervous system with meningeal metastases visualized on 68Ga-DOTATOC imaging.

Meckel's diverticulum in infants and children; technetium-99m pertechnetate scintigraphy and clinical findings.

Meckel's diverticulum (MD) is the most common congenital gastrointestinal anomaly. About 50% of diverticulae contain ectopic gastric mucosa. Gastric mucosal secretions can cause peptic ulceration resulting in pain, bleeding and perforation. Technetium-99m ((99m)Tc) pertechnetate scintigraphy is helpful in diagnosing ectopic gastric mucosa. We have conducted a retrospective analysis of scintigraphic data of 107 pediatric patients, 28 females and 79 males, their age ranging from 5 days to 11 years who referred to us for a query diagnosis of MD. Our results have shown that the most frequent presenting symptom was bleeding per rectum. Twenty-one cases of the 107 were positive for functioning gastric tissue indicating MD (19.62%). Maximum clustering of positive cases was at the age group of 1-2 years (11 cases i.e. 52.38%). The site of the ectopic activity was mainly at the umbilical quatrum in 11 cases (52.4%). Two patients were lost to follow-up and hence surgery could not be performed. The remaining 19 cases were subjected to surgical intervention and 16 were found to be positive for MD. The scintiscan was true positive in 84.2%. Our findings were in agreement with those of other authors. In conclusion, in pediatric patients (99m)Tc-pertechnetate scintigraphy is by 84.2% true positive for gastric mucosa, indicating MD.

Trails on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Leading to Diagnosis of Testicular Adrenal Rest Tumor.

Testicular adrenal rest tumors (TARTs) are secondary to hypertrophy of adrenal rest cells in the rete testis in settings of hypersecretion of androgens. We present a case of congenital adrenal hyperplasia with TART with clues to the diagnosis on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). To the best of our knowledge, this is the first reported case on the role of 18F-FDG PET/CT in TART.

Rare Involvement of Thyroid Cartilage and Thyroid Gland by Multiple Myeloma on 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Multiple myeloma commonly involves the skeleton. Extraosseous disease is sometimes noticed involving various organs. We present a very unusual site of myeloma involvement in the thyroid gland and thyroid cartilage.