Safety and Efficacy of 177Lu-DOTATATE in Children and Young Adult Population: A Single-Center Experience.

PURPOSE: This single-center retrospective study explores the safety and efficacy of 177Lu-DOTATATE in children and young adult population with metastatic/inoperable neuroendocrine tumors (NETs). PATIENTS AND METHODS: This study is a retrospective analysis of all children and young adult patients (≤29 years) with advanced inoperable/metastatic epithelial or nonepithelial NETs who were administered a median of 4 cycles of 177Lu-DOTATATE therapy and low-dose oral capecitabine as a radiosensitizer every 8-12 weeks, except 2 patients who received CAPTEM chemotherapy. The radiological response was assessed using RECIST 1.1 on interim and end-of-treatment 68Ga-DOTANOC PET/CT. The primary endpoint was objective response rate, whereas disease control rate, toxicity profile, progression-free survival, and overall survival were secondary endpoints. RESULTS: Nineteen biopsy-proven NET patients (median age, 22 ± 10 years) with 8 of them adolescents (10-18 years) and the remaining young adults (19-29 years) were included. Fourteen patients had gastroenteropancreatic neuroendocrine tumor (pancreas being most common primary site), whereas the rest had non-gastroenteropancreatic neuroendocrine tumor. A total of 65 cycles of 177Lu-DOTATATE (range, 1-6 cycles) were administered with a median cumulative activity of 600 mCi (range, 100-1000 mCi). The objective response rate and disease control rate were 41% and 94%, respectively. Grade 1 and 2 adverse events were observed in 14 (74%) and 5 (26%) of 19 patients, respectively. In a total of 8 events (42%), 4 events each of disease progression and death occurred during a median follow-up of 80.1 months with an estimated 5-year progression-free survival and overall survival of 54% (95% confidence interval, 30-78) and 63% (95% confidence interval, 39-87), respectively. CONCLUSIONS: 177Lu-DOTATATE appears safe and effective in children and young adults with metastatic/inoperable NETs. Large prospective trials are required to validate these results.

Prostate-Specific Membrane Antigen-Avid Neurofibroma Mimicking Cutaneous Metastasis in Metastatic Castration-Resistant Prostate Cancer on 18 F-PSMA-1007 PET/CT.

ABSTRACT: The occurrence of cutaneous metastases in prostate cancer is exceedingly rare. Many benign lesions and nonprostatic cancers can express the prostate-specific membrane antigen (PSMA). They can potentially mimic metastasis of prostate cancer and lead to misinterpretation of PSMA PET/CT findings. Additionally, it has significant management and prognostic implications. We present a rare case of an 88-year-old man with metastatic castration-resistant prostate cancer who showed a PSMA-expressing subcutaneous nodule in the scalp on 18 F-PSMA-1007 PET/CT, raising the suspicion of cutaneous metastasis. However, its biopsy revealed a neurofibroma, altering the disease prognosis and management.

Annotating the Role of 18F-FDG PET/CT in Fibromatoses: A Benign Masquerader of Malignancies-Is It Really an Advantageous Tool?

Fibromatoses are a heterogeneous group of benign proliferating fibroblasts and myofibroblasts which have a high predilection for recurrence and local invasion, especially deep fibromatoses or desmoid fibromatosis. 18F-FDG PET/CT, the workhorse of oncological imaging in nuclear medicine, can be employed to figure out the nature and aggressiveness of the lesions and various sites of involvement and to monitor treatment response to systemic therapies like tyrosine kinase inhibitors in case of deep or desmoid fibromatoses which is shown in the current research work.

Incidentally Detected Gallbladder Carcinoma: Can F-18 FDG PET/CT Aid in Staging and Prognostication?

Purpose: Incidental gallbladder carcinoma (IGBC) is diagnosed in post-cholecystectomy specimens for benign indications, where the role of 2-fluro-2-deoxyglucose positron emission tomography/computed tomography(FDG-PET/CT) is not clearly defined. The present study aimed to assess the benefits of staging and prognosticating with FDG-PET/CT in IGBC. Materials and Methods: A retrospective observational study from a tertiary-care center from January 2010 to July 2020 was performed. The demographic, clinical, histopathological, and treatment-related histories were collected. FDG-PET/CT-image findings were compared with survival outcomes through telephonic follow-up. The chi-square test was used for comparing frequencies. The univariate and multivariate survival estimates were analyzed using the Kaplan-Meier analysis and the Cox-proportional hazard model, respectively. Log-rank test was used to compare the Kaplan-Meier curves. Results: The study included 280 postcholecystectomy participants (mean age: 52 ± 11 years; women: 227) of whom 52.1% had open surgery(146/280). Residual disease in the gallbladder fossa (54.8% vs. 36.6%, p = 0.002) and liver infiltration (32.9% vs. 22.4%, p = 0.05) were seen more frequently in open surgery compared to laparoscopic surgery, while anterior abdominal wall deposits were more common in laparoscopy(35.1% vs. 24%,p = 0.041). FDG-PET/CT changed the management in 10% (n = 28) of patients compared to contrast-enhanced CT. The median survival was 14 months (95%CI-10.3-17.7). A higher stage of the disease on the FDG-PET/CT (loco-regional disease-HR 4.86, p = 0.006; metastatic disease-HR 7.53, p < 0.001) and the presence of liver infiltration (HR-1.92, p = 0.003) were independent predictors of poor survival outcomes. Conclusion: FDG-PET/CT detects residual and metastatic disease in patients with IGBC, enabling the institution of appropriate management and acting as a tool for prognostication of survival.

FDG PET/CT in the Diagnosis and After Sunitinib Follow-up of Synchronous Base of Tongue and Thyroid Metastases From Renal Cell Carcinoma.

ABSTRACT: Renal cell carcinoma (RCC) is a leading cause of mortality among genitourinary malignancies with limited therapeutic options. The hematogenous route, lymphatic spread, and direct invasion have been documented in RCC. Usually, metastases are regional lymph nodes, lungs, bone, liver, adrenal glands, contralateral kidney, and brain. Metastases to the rare sites such as skin, breast, head and neck were documented in the literature. In the present case, we describe the synchronous metastases to the base of the tongue and thyroid gland in RCC and the response to sunitinib therapy on 18F-FDG PET/CT.

177 Lu-DOTATATE Salvage Therapy in Rapidly Progressing Neuroendocrine Tumor With Poor Performance Status.

ABSTRACT: Peptide receptor radionuclide therapy (PRRT) has shown to be effective and safe in metastatic gastroenteropancreatic and nongastroenteropancreatic neuroendocrine tumors. However, the selection criteria for PRRT are restricted to patients with good performance status (Eastern Cooperative Oncology Group score ≤2 or Karnofsky performance score ≥60). This denies many patients with adequate somatostatin receptor expression and biochemical profiles from the beneficial effects of PRRT on the quality of life, daily function, and overall survival. The 2 cases highlight the favorable response of PRRT in patients with metastatic neuroendocrine tumor having a very poor performance status initially.

68 Ga-FAPI PET/CT in an Interesting Case of Metastatic Pulmonary Meningioma.

ABSTRACT: Meningiomas are one of the major primary CNS tumors. Most meningiomas are benign, but rarely, these metastasize to distant organs, the lungs being the commonest site of metastasis. 18 F-FDG PET/CT has been used to evaluate metastatic pulmonary meningioma. However, 68 Ga-FAPI PET/CT has not yet been evaluated. The present case highlights the 68 Ga-FAPI uptake in metastatic pulmonary meningioma in a postoperated case of left tentorial meningioma presenting with lung masses. Image-guided biopsy from the lung mass was consistent with metastatic meningioma.

Unusual Sites of Visceral Spread in Prostate Cancer: A Prostate-Specific Membrane Antigen-Based Theranostic Imaging Series.

ABSTRACT: Prostate cancer commonly metastasizes to lymphatic and skeletal systems with lesser frequency to visceral organs; however, uncommon visceral sites have also been found and reported as case reports. We present a series of uncommon metastatic visceral spread in prostate cancer on prostate-specific membrane antigen-based diagnostic and posttherapeutic imaging modalities.

Convoluted Neural Network for Detection of Clinically Significant Prostate Cancer on 68 Ga PSMA PET/CT Delayed Imaging by Analyzing Radiomic Features.

Purpose: To assess the utility of convoluted neural network (CNN) in differentiating clinically significant and insignificant prostate cancer in patients with 68 Ga PSMA PET/CT-targeted prostate biopsy-proven prostate cancer. Methods: In this retrospective study, 142 patients with clinical suspicion of prostate cancer were evaluated who underwent 68 Ga-PSMA PET/CT imaging followed by 68 Ga-PSMA PET/CT-targeted prostate biopsy from the PSMA-avid prostate lesion. Twenty patients with no PSMA-avid lesions were excluded. Local Image Features Extraction (LifeX) software was used to extract radiomic features (RF) from delayed 68 Ga-PSMA PET/CT images of 122 patients. LifeX failed to extract radiomic features in 24 patients, and the remaining 98 were evaluated. RFs were fed to an in-built CNN of the software for computation and results were achieved. Patients with Gleason Score ≥ 7 on histopathology were labeled clinically significant prostate cancer (csPCa). The diagnostic values of radiomic features were evaluated. Results: The csPCa was revealed in 69/98 (70.4%) patients, and insignificant PCa was noticed in 29/98 (29.6%) patients. The software extracted 124 RF from the delayed 68 Ga-PSMA PET/CT images. The accuracy of the CNN was 80.7% to differentiate clinically significant and clinically insignificant prostate cancer, with an error percentage (E %) of 19.3%. The sensitivity, specificity, positive predictive, and negative predictive values were 90.3%, 57.7%, 83.6%, and 71.4%, respectively, to detect csPCa. Conclusion: CNN is a feasible pre-biopsy screening tool for identifying clinically significant prostate cancer and can be used as an adjunct in the initial diagnosis and early treatment planning. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-023-00832-3.

18 F-FDG PET/CT in Lupus Enteritis Presenting With Fever and Abdominal Pain.

ABSTRACT: Systemic lupus erythematosus is a systemic autoimmune disease associated with various manifestations. Here, we report a compelling case of a 42-year-old woman who presented with lupus enteritis as a sole manifestation of systemic lupus erythematosus and underwent 18 F-FDG PET/CT. The resected bowel segment revealed vasculitis, and subsequent workup revealed positive antinuclear and anti-double-stranded antibody levels, confirming lupus enteritis, thus highlighting the diagnostic role of 18 F-FDG PET/CT in reaching the final diagnosis.

Potential application of 68Ga-FAPI PET/CT for diagnosing cardiac sarcoidosis.

Detecting cardiac sarcoidosis; a potentially life-threatening condition is challenging and requires a multimodality imaging approach using echocardiography, PET/CT and CMR. Although 18F-FDG is the recommended PET tracer for evaluating cardiac sarcoidosis, it is limited by physiological cardiac FDG uptake and requires stringent patient preparation/ dietary modifications before imaging. We hereby present a case of cardiac sarcoidosis demonstrating myocardial FAPI uptake on cardiac PET, highlighting the potential role of 68Ga-FAPI PET in the evaluation of cardiac sarcoidosis.

177 Lu-Microspheres Selective Intra-arterial Radionuclide Therapy : A Facile and Biocompatible Permanent Micro-Seed Implants for Unresectable Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is an aggressive malignancy with a poor prognosis. Surgical resection is limited. Selective intra-arterial radionuclide therapy (SIRT) emerged as a potential cure for intermediate HCC with portal vein thrombosis. We report a pilot study of a 48-year-old man with recurrent HCC who underwent 177 Lu-microsphere SIRT (2.2 GBq) in segment III. Posttherapy SPECT/CT images (24 hours to 3 months) demonstrated excellent localization and prolonged retention within the tumor. Pre- and 3-month post-SIRT CECT showed a notable decrease in arterial enhancement and tumor size. Time-activity curve of the standard and the lesion demonstrated similar decay pattern indicating that 177 Lu-microspheres act as permanent implant.

Unraveling Interaction of Rhenium-188 Microspheres with Primary Hepatic Cancer Cell: A Breakthrough Study.

Introduction: Hepatocellular carcinoma is a prevalent contributor to global mortality rates. The main palliative treatments are trans-arterial chemoembolization and selective intra-arterial radionuclide therapy. Methods: A novel freeze-dried nonradioactive microsphere kit formulation has been developed, and the behavior and therapeutic potential of 188Re microspheres have been assessed. The microspheres were labeled with fluorescein isothiocyanate (FITC) and 188ReO4-. The uptake of FITC microspheres by HepG2 cells was examined at various time intervals. The impact of 188Re microspheres on cell viability and the mode of cell death were investigated with HepG2 cells using MTT and Annexin FITC-V/propidium iodide (PI) apoptosis assay. Results: The labeling efficiency of microspheres was more than 99% with FITC and 188ReO4-. The maximum uptake of FITC microspheres by HepG2 cells was achieved at 6 h. The exposure to 188Re microspheres has shown a decrease in cellular viability from 77.81% ± 0.015% to 42.03% ± 0.148% at 192 h of incubation (∼11 half-lives). The cellular uptake of 188Re microspheres was 0.255-0.901 MBq. These values were concordant with Annexin FITC-V/PI apoptosis assay. At 192 h, 53.28% ± 0.01% of cells entered the apoptotic phase after treatment with 188Re microspheres, and only 39.34% ± 0.02% of cells remained viable. However, in the cells treated with 188ReO4- alone, 74.86% ± 0.005% of cells were viable, and only 24.75% ± 0.577% of cells were in the early apoptotic phase at 192 h. Conclusion: The data revealed that 188Re microspheres treatment led to significant growth inhibition in HepG2 cells compared with 188ReO4-.

Tubarial salivary glands on PSMA ligands based PET imaging and post 177Lu PSMA therapy scan: reiterating its importance.

68Ga-PSMA PET/CT has been routinely utilized in patients with intermediate to high-risk category prostate carcinoma for staging, biochemical recurrence and before planning the PSMA radioligand therapy (RLT). 177Lu-PSMA RLT has also been approved by FDA as a novel treatment modality in metastatic carcinoma prostate patients who have failed to other lines of treatment. The non-target organs like salivary and lacrimal glands have shown to have high physiological PSMA uptake on PSMA PET/CT. Recently, strong uptake of PSMA ligand has also been noted in the dorsal wall of the nasopharynx in the region of torus tubarius on PSMA PET/CT, which has led to the identification of new pair of salivary gland structures called "tubarial salivary glands". The clinical significance of these distinct anatomical structures lies in the fact these structures might be involved in a variety of immune related, inflammatory disorders, malignancies and could be a probable organ at risk during radiotherapy in case of head and neck malignancies, causing adverse effects to the patient.

68Ga-DOTA.SA.FAPi as a Versatile Diagnostic Probe for Various Epithelial Malignancies: A Head-to-Head Comparison with 18F-FDG.

RATIONALE AND OBJECTIVES: Fibroblast Activation Protein (FAP) expressing cancer-associated fibroblasts has been a major breakthrough causing a paradigm shift in targeted theranostics focusing on the tumor microenvironment. In this study, a squaric acid derivative DOTA.SA.FAPi (SA.FAPi) has been evaluated as a potential diagnostic probe in diverse epithelial cancers and compared to the standard-of-care 18F-FDG. METHODS: 25 patients enrolled in this prospective study underwent 18F-FDG and 68Ga-SA.FAPi PET scans on two different days. For biodistribution, standardized uptake values (SUV) were computed by delineating region-of-interest on various body organs. For comparative analysis in disease identification, lesion tracer uptake was quantified using SUVs corrected for lean body mass (SUL), SUVmax, tumor-to-background ratio (TBR) with liver and blood pool as the reference, total lesion glycolysis (TLG for 18F-FDG) and total lesion FAP expression (TLF for 68Ga-SA.FAPi). RESULTS: 25 patients (mean age: 58 ± 8 years) with four types of cancers including hepatocellular carcinoma (HCC, 56% of cohort), gall bladder carcinoma (GB Ca, 12%), adrenocortical carcinoma (ACC, 16%), and breast carcinoma (breast Ca, 16%) were prospectively evaluated. Physiological tracer uptake of 68Ga-SA.FAPi was noted in the salivary glands, thyroid, liver, pancreas, muscles and kidneys with variable uptake in the lacrimal glands, extra-ocular muscles, oral mucosa and uterus. Lesion-based comparative analysis between both the radiotracers demonstrated complete concordant findings in detection of all primary lesions and distant metastases in liver, bones, adrenals and peritoneum whereas discordant findings were noted in lung nodules (20%) and lymph nodes (13%). In overall analysis, 68Ga-SA.FAPi exhibited significantly higher SUVmax (10.3 vs 8.8, p-0.019), SULpeak (6.8 vs 4.9, p-0.000) and SULavg (5.4 vs 4.1, p-0.019) in comparison to 18F-FDG whereas TBR was comparable for both the tracers [TBRLiver: median 1.9 (IQR: 2.6-1.4) vs 1.8 (2.6-1.1), p-0.275; TBRBloodpool: 2.1 (3.7-1.4) vs 2.0 (2.7-1.4), p-0.207]. In subcategorical analysis, 68Ga-SA.FAPi demonstrated higher SUVmax, SULpeak and SULavg values for primary disease (SUVmax: 14.8 (18.7-9.7) vs (12.9-6.6), p-0.087; SULpeak: 8.2 (11.2-6.8) vs 6.3 (8.5-4.4), p-0.037; SULavg: 6.9 ± 2.5 vs 5.1 ± 2.2, p-0.023] and distant metastases (8.8 vs 7.2, p-0.038); 6.3 (8.8-4.4) vs 3.6 (4.4-2.0), p-0.000; 5.4 vs 3.5, p-0.000] whereas comparable values were noted for both the tracers in nodal metastases [9 (13.5-4.1) vs 8 (12.7-4.7), p-0.726; 4.5 (6.2-1.8) vs 4.3 (5.7-2.2), p-0.727; 4.1 ± 2.3 vs 3.7 ± 1.8, p-0.129]. In primary disease, highest 68Ga-SA.FAPi avidity was noted in ACC followed by GB Ca and HCC. In distant metastases, gall bladder, lung and skeletal lesions demonstrated higher 68Ga-SA.FAPi avidity. Moreover, 68Ga-SA.FAPi identified five additional lung lesions which were missed by 18F-FDG in one case of ACC. CONCLUSION: 68Ga-SA.FAPi emerged as an effective, versatile diagnostic probe for imaging various epithelial malignancies similar to 18F-FDG.

Unusual Perineal Metastasis in a Case of Prostate Cancer on 68 Ga-PSMA-11 PET/CT.

ABSTRACT: Prostate cancer is the fifth leading cause of death in the male population worldwide. 68 Ga-PSMA PET/CT has proved to be an excellent modality with greater accuracy for nodal and bone/visceral metastases staging than bone scintigraphy and CT scan, with high sensitivity and specificity. Common sites of metastasis include bone (84%), lymph nodes (10.6%), liver (10.2%), lung, and pleura (9.1%); however, metastasis to the skin is quite rare (≤0.36%). The present case demonstrates PSMA-avid perineal metastasis in a patient of prostate cancer postchemoradiotherapy on 68 Ga-PSMA PET/CT scan.

68 Ga-PSMA-11 Uptake in a Large Fibroadenoma in a Male Axillary Accessory Breast.

ABSTRACT: Prostate-specific membrane antigen PET imaging has revolutionized the role of prostate cancer diagnosis and management, with very high sensitivity and specificity. To prevent misdiagnosis and for accurate therapy planning, prostate-specific membrane antigen (PSMA) uptake in nonprostatic diseases needs to be recognized correctly. Besides the physiological PSMA expression, 68 Ga-PSMA-11 uptake has been mentioned in multiple oncological and nononcological lesions. The present case report exhibits 68 Ga-PSMA-11 uptake in fibroadenoma in a male accessory breast in the right axillary region.

Potential role of 68Ga-PSMA PET/CT in metastatic renal cell cancer: A prospective study.

PURPOSE: Prostate-specific membrane antigen (PSMA), in addition to its utility in prostate cancer, is also an angiogenic imaging marker for hypervascular tumors like renal cell carcinoma (RCC). Our study aims to assess the potential role of 68Ga-PSMA-11 positron emission tomography (PET)/CT in metastatic RCC and compare it with contrast-enhanced computed tomography (CECT). METHODS: Biopsy-proven RCC patients with known or suspected distant metastases who underwent 68Ga-PSMA-11 PET/CT for staging/restaging were prospectively recruited. Those patients who had undergone 18F-FDG PET/CT within six weeks of 68Ga-PSMA PET/CT were also included retrospectively for comparative analysis. A patient-based and lesion-based analysis was done to compare the lesion detection rates of CECT, 68Ga-PSMA-11 PET and 18F-FDG PET. PET-based quantitative parameters were also compared between both the PET modalities. Impact of baseline parameters on survival was assessed using Cox regression analysis. A p-value of < 0.05 was considered significant. RESULTS: Thirty-seven patients with median age 60 years ± 13 years (range = 26-76 years) were included in the study. Twenty-seven patients had clear cell (cc) RCC, six had papillary RCC (pRCC), and one each had an eosinophilic variant of ccRCC, collecting duct RCC, translocation RCC and poorly differentiated RCC. 68Ga-PSMA-11 PET performed better in detecting marrow and equivocal bone lesions and worse in detecting liver lesions compared to CECT. 68Ga-PSMA-11 PET-based angiogenic tumor burden estimation using Total Lesion-PSMA (TL-PSMA) and PSMA-Total volume (PSMA-TV) had a prognostic impact on the survival of patients. 68Ga-PSMA-11 PET also detected more lesions and showed significantly higher SUVmax than 18F-FDG PET. CONCLUSION: 68Ga-PSMA-11 PET/CT performs better than CECT and 18F-FDG PET/CT in metastatic evaluation and has prognostic value in the management of clear cell RCC.

Estimation of absorbed dose to salivary glands in mCRPC patients undergoing 177 Lu- PSMA-617 radioligand therapy using quantitative SPECT-CT at single time point: a single-center feasibility study.

OBJECTIVE: 177 Lu-PSMA-617-radioligand therapy (RLT) has shown promising therapeutic role in patients with metastatic castration-resistant prostate cancer. However, off-target action in salivary glands often presents with xerostomia. Personalized dosimetry can help in optimizing the treatment, however, has so far been tedious due to multiple time-point imaging. In this prospective study, we intended to estimate the absorbed dose delivered to the salivary glands in patients undergoing 177 Lu-PSMA-617-RLT using quantitative SPECT/CT at a single time point. METHODS: Patients undergoing 177 Lu-PSMA-617 RLT were included in this prospective study. Post-therapy whole-body images and regional quantitative single time-point SPECT/CT were acquired at 24 h with high-energy collimator. The data was processed and analyzed using Q.Metrix software. A scaling factor, that is, the time-integrated activity conversion factor was applied for the image acquired at 24 h. Absorbed doses were computed using MIRD scheme and OLINDA software. RESULTS: A total of 21 patients (mean age: 66 ±â€…9 years) were included. The value of mean absorbed dose for the parotid glands was 1.90 ±â€…1.31Gy (range: 0.26-6.23) and that for the submandibular glands was 1.37 ±â€…0.94Gy (range: 0.16-3.65). The mean absorbed doses per administered activity for the parotid and submandibular glands were 0.26 ±â€…0.18 Gy/GBq and 0.19 ±â€…0.12 Gy/GBq, respectively. The absorbed doses were estimated for one cycle of therapy and were well within acceptable limits. None of the patients experienced dryness of mouth. CONCLUSION: Single time-point dosimetry with quantitative SPECT/CT is feasible and can be standardized to estimate the absorbed dose to salivary glands instead of multiple time-point acquisitions.

Sunitinib in Tandem With 177 Lu-DOTATATE Therapy in Advanced Pancreatic Neuroendocrine Tumor : A New Treatment Approach.

ABSTRACT: Various systemic treatment options are available for advanced pancreatic neuroendocrine tumors (NETs); however, individual treatment may be suboptimally effective. Sunitinib inhibits multiple kinases and signaling pathways with delay in tumor growth, whereas peptide radioreceptor therapy (PRRT) delivers targeted radiation to the tumors in pancreatic NETs. There is a dearth of literature on the combined or tandem use of these systemic treatment modalities. We present a case of 40-year-old man with advanced pancreatic NET where PRRT or sunitinib as monotherapy had a suboptimal treatment response, but the use of sunitinib in tandem with 177 Lu-PRRT reinforced the response to the treatment.