Feasibility and therapeutic potential of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma.

INTRODUCTION: The unique expression pattern of fibroblast activation protein (FAP) in stromal and tumor cells, particularly in sarcomas, and its absence in normal tissues, have positioned it as a promising theragnostic approach for the detection and treatment of various cancer types. The objective of this prospective study is to assess the feasibility, safety, biodistribution, and therapeutic efficacy of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma. PATIENTS AND METHODS: Eight patients with advanced metastatic sarcoma, who were unresectable or had experienced disease recurrence following conventional treatments, underwent PTRT (peptide-targeted radionuclide therapy) using [177Lu]Lu-FAPI-2286. Prior to the treatment, confirmation of tumor uptake was obtained through [68Ga]Ga-FAPI-2286 PET/CT. RESULTS: After four cycles of PTRT with [177Lu]Lu-FAPI-2286 (6660-7400 MBq), with a 6-8-week interval between each cycle, no grade 3 or 4 side effects were observed in the patients, and the treatment was well tolerated by all participants. The results demonstrated a 52.37% reduction in the average volume of the primary tumor, accompanied by a significant decrease in SUVmax and TBR of the metastatic lesions (29.67% and 43.66% respectively), especially in cases of lung metastasis. Furthermore, besides the improvement in physical capacity, there was a noticeable reduction in pain, an increase in overall survival, and enhanced satisfaction with the treatment reported by the patients. CONCLUSION: [177Lu]Lu-FAPI-2286 PTRT, utilized for diverse cancer types, exhibited favorable tolerability in sarcoma patients, with minimal side effects, long-lasting retention of the radiopeptide within the tumor, and promising therapeutic effects. Preliminary findings of this prospective study need to be confirmed through further clinical trials.

[68Ga]Ga-FAP-2286, a novel promising theragnostic approach for PET/CT imaging in patients with various type of metastatic cancers.

BACKGROUND: Fibroblast activation protein (FAP) has emerged as a promising target for diagnosis and therapeutic intervention due to high expression and accumulation in the stromal compartments of a variety of malignant tumors. FAP-2286 utilizes cyclic peptides with FAP-binding characteristics to enhance the retention of the imaging agent within tumors, in contrast to the small-molecule FAP inhibitors (FAPI) like FAPI-04/46. The aim of this study was to quantify the tumor uptake of [68Ga] Gallium-FAP-2286 within primary solid tumors, adjacent excised tissues, and metastatic lesions. METHODS: In this prospective study, 21 patients (average age 51.9) with various diagnoses of remaining and metastatic cancers participated. Among them, six had metastatic sarcoma, and 14 had adenocarcinoma, including eight breast, two rectum, two lung, two pancreas, and one thyroid cases. The patients underwent a [68Ga]Ga-FAP-2286 PET/CT scan. An hour post-administration of [68Ga]Ga-FAP-2286, a visual assessment of whole body scans and semi-quantification of the PET/CT results were carried out. The standardized uptake values (SUV)max of [68Ga]Ga-FAP-2286 in tumor lesions and the tumor-to-background ratio (TBR) were then calculated. RESULTS: The vital signs of the patients, such as heart rate, blood pressure, and temperature, were observed before, during, and after the diagnostic procedure during the 4-h follow-up. All individuals underwent the [68Ga]Ga-FAP-2286 PET/CT scans without any signs of drug-associated pharmacological effects. The PET/CT scans displayed substantial absorption of [68Ga]Ga-FAP-2286 in tumor lesions in all patients (100% (21/21)). Irrespective of the tumors' origins (epithelial or mesothelium) and whether they exhibited local recurrence, distant recurrence, or metastatic lesions, the PET/CT scans revealed the uptake of [68Ga]Ga-FAP-2286 in these lesions. CONCLUSION: Overall, these data suggest that [68Ga]Ga-FAP-2286 is a promising FAP derivative for efficient metastatic cancer diagnosis and being considered as a potential compound for therapeutic application in patients with advanced metastatic cancers.

Effect of proton pump inhibitors and H2 antagonists on gastric wall uptake in myocardial perfusion scan with 99mTc-sestamibi.

BACKGROUND: Proton pump inhibitors (PPIs) have been speculated to cause gastric wall uptake (GWU) in MPI scans. However, the uptake mechanism and prevention methods are less studied. In this prospective trial we aimed to evaluate the impact of gastroprotective medications on GWU and its solutions. METHODS: 351 consecutive patients, scheduled for 2-day rest/stress 99mTc-MIBI scan, were distributed into 5 groups. 3-7 days following the baseline rest scan, the stress scan was acquired after intervention in the trial group, consisting of patients with history of PPI intake, randomly assigned to 3 subgroups: discontinuing PPIs(A), replacement with H2 blockers (B), and continuing PPIs (C). Patients receiving H2 blockers, continued it as before (D) and the remaining patients were the control group (E). GWU was graded compared to the myocardial uptake. RESULTS: In the rest phase, all groups had significantly higher GWU compared to the control group. In the stress phase, group A had less GWU than group B (P-value < 0.05) and both of them had significantly less GWU compared to group C (P-value < 0.001). There was no significant difference between PPI discontinuation periods of 3-5 days versus 5-7 days. There was a significant association between duration of oral PPI intake, but not IV PPIs, and GWU. GWU was significantly lower with oral compared to IV PPI administration. CONCLUSION: PPIs significantly increase GWU and discontinuing them for at least 3-5 days significantly reduces GWU. H2 antagonists are a good alternative in patients who cannot tolerate dyspepsia symptoms.

First Experience of Radionuclide Therapy With 177Lu-FAPI-2286 in a Patient With Metastatic Mediastinal Sarcoma.

ABSTRACT: Fibroblast activation protein (FAP) is a new promising molecular target for theragnostic approach. FAP inhibitors (FAPIs) labeled with 177Lu could be potentially a therapeutic radiopharmaceutical. Here, we presented the experience of 4 cycles of 177Lu-FAPI in a 67-year-old man with an unresectable mediastinal sarcoma.

Metachronous Brain Tumor in 177Lu-PSMA Scan in a Patient with Metastatic Castration Resistant Prostate Cancer Mimicking Disease Progression.

A 66-year old man known case of metastatic castration resistant prostate cancer underwent successful 6 cycles treatment with 177Lu- prostate-specific membrane antigen. On the last post therapy whole body scan a new lesion in the skull was noted, suspected for disease progression. One week later, the patient complained from weakness of left upper extremity and brain magnetic resonance imaging revealed a brain tumor, confirmed as glioblastoma pathologically.

Utility of 99mTc-Sestamibi Heart/Liver Uptake Ratio in Screening Nonalcoholic Fatty Liver Disease During Myocardial Perfusion Imaging.

Purpose: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic hepatic disease worldwide, with functional impairment of the mitochondria occurring from early stages. Technetium-99m methoxy-isobutyl-isonitrile (99mTc-MIBI) is a lipophilic agent trapped in the mitochondria. This study aims to evaluate the utility of 99mTc-MIBI heart/liver uptake ratio in screening for NAFLD during myocardial perfusion imaging (MPI). Methods: Seventy eligible patients underwent a 2-d rest/stress 99mTc-MIBI scan with a 2-min planar image acquired in rest phase, at 30, 60, and 120 min postradiotracer administration. Heart/liver uptake ratio was calculated by placing identical regions of interest on the heart and liver dome. All patients underwent liver ultrasound and were allocated into groups A, having NAFLD; and B, healthy individuals without NAFLD. Results: Mean count per pixel heart/liver ratios gradually increased over time in either group; nonetheless the values were significantly higher in group A, regardless of acquisition timing; with the p-value equal to 0.007, 0.014, and 0.010 at 30, 60, and 120 min, respectively. Conclusion: Determining 99mTc-MIBI heart/liver uptake ratio during rest phase in patients undergoing MPI may be a useful, noninvasive screening method for NAFLD; with no additional cost, radiation burden, or adverse effects in these patients. Trial registration number: IR.SBMU.MSP.REC.1398.308.

Radioiodine-Avid Paravertebral Bronchogenic Cyst Mimicking Neurofibroma: A Diagnostic Pitfall.

ABSTRACT: The whole-body postablation scan of a 38-year-old man, with history of papillary thyroid cancer, revealed a focus of intense 131I accumulation about the lower thoracic vertebrae. SPECT/CT revealing a soft tissue lesion adjacent the T9 to T10 vertebrae, which was reported as neurofibroma on the subsequently performed MRI. However, the lesion was confirmed as a bronchogenic cyst on biopsy. Respecting that unlike neurofibroma, immunohistochemistry studies have confirmed Na-I symporter expression in bronchogenic epithelium; our case highlights that, although rare, paravertebral bronchogenic cysts should be considered in differential diagnosis of radioiodine-avid paravertebral lesions.

Comparison of Accuracy in Calculation of Absorbed Dose to the Kidneys Following Radioligand Therapy with 177Lu-DKFZ-PSMA-617 by Two Different Background Correction Methods.

Background: To improve the accuracy of activity image quality, scatter correction is a critical method. The aim of this study is to compare the accuracy in calculation of absorbed dose to patients following radioligand therapy (RLT) with 177Lu-DKFZ-PSMA-617 by two different methods of background correction in the conjugate view method. Materials and Methods: This study involved 10 patients. The individualized patient dosimetry calculations were based on whole-body planar scintigraphy images acquired in 10 patients with a mean age of 71.4 ± 6.07 years (range 63-85 years) at approximately 0-2 h, 4-6 h, 18-24 h, and 36-48 h after administration of the mean 6253 ± 826.4 MBq (range 5500-7400 MBq) of 177Lu-DKFZ-PSMA-617. Organ activities were calculated using the conjugate view method by Buijs and conventional background correction. Eventually, the absorbed dose of radiation was calculated using Medical Internal Radiation Dose formalism. Results: The dose per unit of injected activity (mGy/MBq) ± standard deviation for kidney using Buijs and conventional methods was 1.05 ± 0.11 and 0.63 ± 0.14, respectively. Conclusion: The Buijs background correction method was more accurate than the conventional method.

Radiation Dose to Medical Staff from Administering 177Lu-PSMA-DKFZ-617 Therapy.

The number of radioligand therapy applications for metastatic castration-resistant prostate cancer has been continuously rising in most nuclear medicine departments in Iran, but to our knowledge, no one has studied the dose to staff who perform treatment procedures. The current study aimed to determine the external radiation dose received by staff who, using or not using a lead shield, treat patients with 177Lu-prostate-specific membrane antigen therapy. Methods: This study used a personal thermoluminescent digital survey meter to measure dose rates to staff at various distances from patients and determined the average time spent by staff at these distances. The deep-dose equivalent to staff was obtained. Results: The measured deep-dose equivalent to staff per patient was within the range of 1.8-5.2 mSv using a 2-mm lead shield and 3.3-8.1 mSv not using the shield. The shield markedly reduced the external dose to staff. Conclusion: The skill and accuracy of staff, and the speed with which they act, can directly affect their received dose.

Parathyroid Carcinoma With Marked Uptake of 99mTcO4.

ABSTRACT: A 51-year-old man with a palpable neck mass and elevated parathyroid hormone was referred to our department for parathyroid scintigraphy. After injection of 740 MBq 99mTc-MIBI, a dual-phase scan was obtained, which revealed a persistent and intense focal hyperactivity in the left side of the neck (compatible with the neck mass). Thyroid scan with 99mTcO4- also showed increased uptake of the mass, similar to a hot thyroid nodule. After surgery, parathyroid carcinoma was confirmed pathologically. This case demonstrates a rare presentation of parathyroid carcinoma as a hot nodule in thyroid scan, which has been attributed to hypervascularity of the lesion.

Patient-Specific Dosimetry in Radioligand Therapy (RLT) for Metastatic Prostate Cancer Using 177Lu-DKFZ-PSMA-617.

PURPOSE: 177Lu-DKFZ-PSMA-617 is a promising treatment for patients with metastatic prostate cancer. Specific dosimetry for each patient is an important factor in planning the patient's treatment process. This study aimed to perform an image-based absorbed dose calculation for the treatment of metastatic prostate cancer with 177Lu-DKFZ-PSMA-617. METHODS: The individualized patient dosimetry calculations were based on whole-body planar scintigraphy images acquired in 10 patients with a mean age of 71.4 ± 6.07 years (range 63-85 years) at approximately 0-2 h, 4-6 h, 18-24 h, and 36-48 h after administration of the mean 6253 ± 826.4 MBq (range 5500-7400 MBq) of 177Lu-DKFZ-PSMA-617. Time-activity curves were generated for various organs. For count conversion to activities, calibration factors were calculated. Finally, the absorbed dose for an individual cycle was calculated using IDIAC-DOSE 2.1 software. RESULTS: On average, the calculated absorbed dose for the kidneys and salivary glands were 0.46 ± 0.09 mGy/MBq and 0.62 ± 0.07 mGy/MBq, respectively. CONCLUSIONS: Based on the results, the177Lu-PSMA-617 therapy is a safe method for the treatment of castration-resistant prostate cancer patients. Large inter-individual variations in organ dose were found, demonstrating the need for patient-specific dosimetry and treatment planning.

Radioligand Therapy With 177Lu-Prostate-Specific Membrane Antigen in a Patient With Non-Prostate-Specific Antigen-Secreting Metastatic Prostate Cancer.

Progression of prostate cancer and prostate-specific antigen (PSA) elevation are closely associated. In fewer than 1% of all cases, disease progression may occur despite low or undetectable PSA levels. In these conditions, androgen deprivation therapy is relatively ineffective, and the prostate cancer progresses very quickly. We present a 65-year-old man with non-PSA-secreting prostate cancer and widespread metastases with rather fair response to Lu-prostate-specific membrane antigen radioligand therapy.

Obscured Meckel's Diverticulum by the Urinary Bladder: The Value of Lateral View and Post Void Images.

We describe a case of a 5-year-old boy with a history of intermittent melena underwent TcO4 scintigraphy. On dynamic images, no abnormal activity was noted. After voiding and also in the lateral view, the focus of activity was noted in the superior and anterior aspect of the urinary bladder, compatible with a Meckel's diverticulum, which was confirmed pathologically as well.

Excellent Response to Lower Dose of 177Lu-PSMA-617 in a Metastatic Castration-Resistant Prostate Cancer Patient With a Transplanted Kidney.

A 68-year-old man with metastatic castration-resistant prostate cancer and widespread bone metastases as well as a history of kidney transplant, underwent 5 cycles of Lu-prostate-specific membrane antigen 617 therapies in our department. Being more cautious of the radiation burden imposed on the transplanted kidney, a lower average dose of 4 GBq per cycle was administered (instead of the more routine 6.0-7.4 GBq per cycle). However, excellent response was noted and serum creatinine level of 0.8 mg/dL remained stable.

177Lu-PSMA and 177Lu-DOTATATE Therapy in a Patient With Metastatic Castration-Resistant Prostate Cancer and Neuroendocrine Differentiation.

We presented a promising result of radionuclide therapy using Lu-PSMA and Lu-DOTATATE in a patient with prostatic adenocarcinoma and neuroendocrine differentiation. Functional imaging of somatostatin receptors in patients with metastatic castration-resistant prostate cancer may pave the way toward implementation of novel radionuclide targets for the treatment of this aggressive subtype of prostate cancer.

Efficacy and safety of 177Lutetium-prostate-specific membrane antigen therapy in metastatic castration-resistant prostate cancer patients: First experience in West Asia - A prospective study.

Prostate-specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed on the surface of prostate cancer (PC) cells, making it an excellent radiotracer for both therapeutic and diagnostic purposes. In this prospective study, we investigated the efficacy and toxicity of 177Lutetium (Lu)-PSMA in metastatic castration-resistant PC (mCRPC) patients for the establishment and approval of this therapy in Iran. Fourteen mCRPC patients (mean age 70.57 ± 7.3 years) were treated with a single dose of 177Lu-PSMA. Complete blood count, liver function tests (aspartate aminotransferase and alanine aminotransferase), alkaline phosphatase levels, renal function tests (urea and creatinine), and prostate-specific antigen (PSA) levels were obtained for the patients at baseline and every 2 weeks. A majority of the patients (11 patients, 64.2%) experienced a decline in their PSA levels; in 5 (45.4%) of these patients, the PSA levels declined > 50%.The severity of pain decreased in 8 (57.1%) patients, and performance status was improved in 5 (45.4%) patients. The treatment was well tolerated, and no severe hematological or nonhematological side effects were observed. Our findings show that 177Lu-PSMA had a high efficacy and a low toxicity in an Iranian population and is a promising treatment option for PC patients.

Prostate-Specific Membrane Antigen in Low-Grade Fibromatosis.

We report a case of fibromatosis demonstrating prostate-specific membrane antigen (PSMA)-positive scan. A 76-year-old man was under assessment because of rising prostate-specific antigen level. Bone scan showed abnormal soft tissue uptake of Tc-MDP adjacent to the right scapula, compatible with a mass in MRI, thereafter. Because of the unavailability of Ga-PSMA scan in our department and also high cost in other centers, the patient underwent Lu-PSMA for more assessment, which revealed PSMA-avid mass. Pathologic examination confirmed the diagnosis of low-grade fibromatosis. This report demonstrates another false-positive result of PSMA scan and highlights the importance of pathologic examination.

Detection of Superior Vena Cava Obstruction on Dynamic 99mTc-DTPA Renal Transplant Scintigraphy.

We present an asymptomatic patient with a history of prolonged hemodialysis through a right internal jugular vein catheter who was diagnosed with superior vena cava (SVC) obstruction on 99mTechnetium-diethylenetriaminepentaacetic acid renal transplant scintigraphy. During the angiographic phase, an unusual vascular filling pattern was detected on the anterior view of the abdomen. Angioscintigraphic imaging of the chest wall was suggestive of SVC obstruction. The SVC obstruction in our patient was related to the long-term use of an indwelling catheter in the central venous system, which is a well-known complication of such a procedure. There is also evidence of a hypercoagulable state in dialyzed uremic cases; therefore, our patient may have been more susceptible to an SVC thrombosis. Acquired compensatory dilatation of the azygos vein is rather a rare finding. To the best of our knowledge, this is the first report describing an asymptomatic patient with SVC obstruction who was diagnosed by renal scintigraphy.

Extradural ganglioneuroma with T1-T2 involvement mimicking spondylodiscitis: a case report and a review of the literature.

Ganglioneuroma (GN) is a rare benign neural tumor, usually derived from the ganglia of the sympathetic system. This report describes a 36-year-old man who presented with back pain and local tenderness that closely mimicked the clinical and ima-ging findings of spondylodiskitis. However, histologic examination made the diagnosis of GN. To our knowledge, this is the first report presenting the pattern of a GN as a differential diagnosis of spondylodiskitis.