Revision of the Histopathological Examination Following 68Ga-DOTA-FAPI-04 PET/CT of a Breast Tumor Diagnosed as Invasive Ductal Carcinomatosis.

Neuroendocrine tumors (NETs) of the breast represent 1% of breast carcinomas. Histopathological misinterpretation of breast NET is common. We present the case of a female patient who had a breast mass diagnosed as invasive ductal carcinoma initially by histopathological examination. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) revealed 2 ametabolic hypodense liver lesions. Subsequently, the patient underwent fibroblast activation protein inhibitor (FAPI)-PET/CT, which did not reveal any FAP expression in the liver lesions, but increased FAP expression was observed in the soft tissue mass of the mesenteric root. Consequently, the pathology of the biopsy taken from the nodule in the right breast was revised, and a diagnosis of grade 2 NET was established. The benefit of FAPI-PET/CT on NETs has been previously investigated. Further prospective studies are required to establish the role of FAPI-PET/CT in NET management.

Adrenal tumors in patients with neuroendocrine neoplasms.

PURPOSE: To study the prevalence of primary adrenal tumors and adrenal metastases in patients with neuroendocrine neoplasms (NENs) and describe these in detail. NENs can be further divided into neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC). METHODS: A review of medical files was conducted for all patients who underwent a 68Gallium-DOTATOC-PET/CT during 2010-2023 or adrenalectomy during 1999-2023 at the Karolinska University Hospital. RESULTS: In total, 68Gallium-DOTATOC-PET/CT was performed on 1750 individuals with NEN, among whom 12 (0.69%) had adrenal tumors. Of these, 9 (0.51%) were NEN metastases. Out of 1072 adrenalectomies, 4 (0.37%) showed evidence of NEN metastases. Thus, 16 patients with NEN exhibited adrenal tumors. The adrenal tumors were found on average 5 years after the NEN diagnosis and 19% of the adrenal tumors with simultaneous NEN were benign. Few had all adrenal hormones measured. None had an adrenal insufficiency nor an adrenal biopsy. Another synchronous metastasis was found in 69% at the time of the adrenal tumor discovery. During the median 2-year follow-up, 38% of the subjects had deceased (with the exclusion of individuals presenting supposedly benign adrenal tumors 31%) all due to tumor complications. A comparison between individuals identified through 68Gallium-DOTATOC-PET/CT and those who underwent adrenalectomy revealed a higher prevalence of NETs in the former group and NECs in the latter group. CONCLUSION: Adrenal primary tumors and adrenal metastases are infrequent occurrences in patients with NEN. Most cases involved the presence of NEN metastasis upon the initial discovery of adrenal tumors. The overall prognosis was found to be favorable.

A comparison study of 68gallium-prostate-specific membrane antigen positron emission tomography-computed tomography and multiparametric magnetic resonance imaging for locoregional staging of prostate cancer.

Purpose: Prostate cancer (PCa) is the most common malignancy in men aged 50 years and older and the second cause of cancer death among men. Accurate staging of PCa preoperatively is of high importance for treatment decisions and patient management. Conventional imaging modalities (ultrasound, computed tomography [CT], and magnetic resonance imaging) are inaccurate for the staging of PCa. Newer modality multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scan show promising results for the staging of PCa. Only fewer studies are available for comparison of these modalities with histopathology as reference. The objective of our study is to evaluate the diagnostic accuracy of independent 68gallium PSMA (68Ga-PSMA) PET-CT compared with mpMRI for preoperative staging of PCa, using histopathology as the reference standard. Materials and methods: From August 2021 to December 2022, 30 patients of biopsy-proven PCa were prospectively enrolled as per eligibility criteria. Preoperatively, 68Ga-PSMA PET scan and mpMRI were done in all the patients. Extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node metastasis (LNM) were investigated separately. Subsequently, the patients underwent robotic-assisted radical prostatectomy with bilateral pelvic lymph node dissection. Results: mpMRI prostate was more sensitive (66.66%) but less specific than PSMA PET-CT (55.55%) for ECE. mpMRI and PSMA PET-CT both had similar sensitivity (83.3%) and specificity (87.5%) for SVI. PSMA PET-CT was more sensitive (85.71%) and specific (95.6%) than mpMRI prostate (62.5% and 91.30%, respectively) for LNM. Conclusion: PSMA PET-CT is more specific for the detection of ECE and more sensitive and specific for the detection of LNM than mpMRI, and similar for the detection of SVI. mpMRI provides only local staging, while PSMA PET-CT provides information about local, regional, and distal staging. Overall, PSMA PET-CT is superior to mpMRI for locoregional staging of PCa.

Hypertensive Crisis in a Patient With a Functioning Mesenteric Paraganglioma: Dramatic Response to Octreotide Treatment.

Background/Objective: To report a dramatic and immediate clinical and biochemical response during treatment with octreotide in a patient with a functioning mesenteric paraganglioma (PGL). Case Report: A 44-year-old woman was admitted with a severe hypertensive crisis and a blood pressure reaching 260/150 mm Hg. She was 2 months postpartum and had been previously diagnosed with pre-eclampsia. Secondary hypertension was suspected. This was confirmed by finding a 6 × 5-cm2 retroperitoneal mass located using 68-Gallium DOTA-octreotate positron emission tomography/computed tomography and a grossly elevated plasma catecholamine level of 93 000 pmol/L (normal reference range: 650-2433 pmol/L). Treatment was immediately started with high doses of long- and short-acting octreotide. After 6 weeks and before surgery, the patient was normotensive, with a blood pressure of 120/70 mm Hg and a norepinephrine level of 6000 pmol/L. The tumor resection was uneventful, and histology confirmed the diagnosis. Following the surgery, the patient remained normotensive without any medications. Discussion: PGLs and pheochromocytomas are neuroendocrine tumors, and most have receptors for octreotide. This case and another patient previously reported responded dramatically to treatment with a high dose of octreotide. Earlier reports of patients failing to respond are likely to have been the result of using a smaller octreotide dose. Conclusion: We conclude that high doses of short- and long-acting octreotide are valuable in severely hypertensive patients. Our experience suggests that octreotide is of value in other patients with PGLs and pheochromocytomas. The response is rapid, sustained, effective, and with minimal reported side effects. To the best of our knowledge, this is the first report of a hypertensive crisis in a functional mesenteric PGL.

Diagnostic Impact of Dual-Time PET/CT with 68Gallium-PSMA in Prostate Cancer and 68Gallium-DOTATOC in Neuroendocrine Tumors.

BACKGROUND: The timing of imaging for 68gallium (68Ga)-PSMA and 68Ga-DOTATOC are stated to be around 60 min post-injection (p.i.). In some lesions, late imaging (3-4 h p.i.) showed advantages. The aim of our evaluation was to demonstrate the relevance of an "early" late acquisition. METHODS: We retrospectively evaluated 112 patients who underwent 68Ga-DOTATOC-PET/CT and 82 patients who underwent 68Ga-PSMA-PET/CT. The first scan was acquired 60 min (±15 min) after application. In cases of diagnostic ambiguity, a second scan was performed 30-60 min later. Pathological lesions were analyzed. RESULTS: Almost half of all 68Ga-DOTATOC cases and about one-third of all 68Ga-PSMA examinations showed a change in findings due to the second acquisition. In total, 45.5% of neuroendocrine tumor (NET) patients and 66.7% of prostate cancer (PCa) patients showed relevant TNM classification changes. For 68Ga-PSMA, there were significant increases in sensitivity and specificity from 81.8% to 95.7% and from 66.7% to 100%, respectively. Statistically significant improvements in sensitivity (from 53.3% to 93.3%) and specificity (from 54.6% to 86.4%) were demonstrated for NET patients. CONCLUSION: Early second images can improve diagnostics with 68Ga-DOTATOC and 68Ga-PSMA PET/CT.

Semi-automated segmentation methods of SSTR PET for dosimetry prediction in refractory meningioma patients treated by SSTR-targeted peptide receptor radionuclide therapy.

OBJECTIVES: Tumor dosimetry with somatostatin receptor-targeted peptide receptor radionuclide therapy (SSTR-targeted PRRT) by 177Lu-DOTATATE may contribute to improved treatment monitoring of refractory meningioma. Accurate dosimetry requires reliable and reproducible pretherapeutic PET tumor segmentation which is not currently available. This study aims to propose semi-automated segmentation methods to determine metabolic tumor volume with pretherapeutic 68Ga-DOTATOC PET and evaluate SUVmean-derived values as predictive factors for tumor-absorbed dose. METHODS: Thirty-nine meningioma lesions from twenty patients were analyzed. The ground truth PET and SPECT volumes (VolGT-PET and VolGT-SPECT) were computed from manual segmentations by five experienced nuclear physicians. SUV-related indexes were extracted from VolGT-PET and the semi-automated PET volumes providing the best Dice index with VolGT-PET (Volopt) across several methods: SUV absolute-value (2.3)-threshold, adaptative methods (Jentzen, Otsu, Contrast-based method), advanced gradient-based technique, and multiple relative thresholds (% of tumor SUVmax, hypophysis SUVmean, and meninges SUVpeak) with optimal threshold optimized. Tumor-absorbed doses were obtained from the VolGT-SPECT, corrected for partial volume effect, performed on a 360° whole-body CZT-camera at 24, 96, and 168 h after administration of 177Lu-DOTATATE. RESULTS: Volopt was obtained from 1.7-fold meninges SUVpeak (Dice index 0.85 ± 0.07). SUVmean and total lesion uptake (SUVmeanxlesion volume) showed better correlations with tumor-absorbed doses than SUVmax when determined with the VolGT (respective Pearson correlation coefficients of 0.78, 0.67, and 0.56) or Volopt (0.64, 0.66, and 0.56). CONCLUSION: Accurate definition of pretherapeutic PET volumes is justified since SUVmean-derived values provide the best tumor-absorbed dose predictions in refractory meningioma patients treated by 177Lu-DOTATATE. This study provides a semi-automated segmentation method of pretherapeutic 68Ga-DOTATOC PET volumes to achieve good reproducibility between physicians. CLINICAL RELEVANCE STATEMENT: SUVmean-derived values from pretherapeutic 68Ga-DOTATOC PET are predictive of tumor-absorbed doses in refractory meningiomas treated by 177Lu-DOTATATE, justifying to accurately define pretherapeutic PET volumes. This study provides a semi-automated segmentation of 68Ga-DOTATOC PET images easily applicable in routine. KEY POINTS: • SUVmean-derived values from pretherapeutic 68Ga-DOTATOC PET images provide the best predictive factors of tumor-absorbed doses related to 177Lu-DOTATATE PRRT in refractory meningioma. • A 1.7-fold meninges SUVpeak segmentation method used to determine metabolic tumor volume on pretherapeutic 68Ga-DOTATOC PET images of refractory meningioma treated by 177Lu-DOTATATE is as efficient as the currently routine manual segmentation method and limits inter- and intra-observer variabilities. • This semi-automated method for segmentation of refractory meningioma is easily applicable to routine practice and transferrable across PET centers.

Diagnostic work-up and advancement in the diagnosis of gastroenteropancreatic neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms ranging from well-differentiated, slowly growing tumors to poorly differentiated carcinomas. These tumors are generally characterized by indolent course and quite often absence of specific symptoms, thus eluding diagnosis until at an advanced stage. This underscores the importance of establishing a prompt and accurate diagnosis. The gold-standard remains histopathology. This should contain neuroendocrine-specific markers, such as chromogranin A; and also, an estimate of the proliferation by Ki-67 (or MIB-1), which is pivotal for treatment selection and prognostication. Initial work-up involves assessment of serum Chromogranin A and in selected patients gut peptide hormones. More recently, the measurement of multiple NEN-related transcripts, or the detection of circulating tumor cells enhanced our current diagnostic armamentarium and appears to supersede historical serum markers, such as Chromogranin A. Standard imaging procedures include cross-sectional imaging, either computed tomography or magnetic resonance, and are combined with somatostatin receptor scintigraphy. In particular, the advent of 111In-DTPA-octreotide and more recently PET/CT and 68Ga-DOTA-Octreotate scans revolutionized the diagnostic landscape of NENs. Likewise, FDG PET represents an invaluable asset in the management of high-grade neuroendocrine carcinomas. Lastly, endoscopy, either conventional, or more advanced modalities such as endoscopic ultrasound, capsule endoscopy and enteroscopy, are essential for the diagnosis and staging of gastroenteropancreatic neuroendocrine neoplasms and are routinely integrated in clinical practice. The complexity and variability of NENs necessitate the deep understanding of the current diagnostic strategies, which in turn assists in offering optimal patient-tailored treatment. The current review article presents the diagnostic work-up of GEP-NENs and all the recent advances in the field.

Report of a Novel Molecular Profile in Malignant Insulinoma.

Pancreatic neuroendocrine tumors, or pNETs, represent a rare and clinically heterogenous subset of pancreatic neoplasms. One such pNET, the insulinoma, is found to be malignant in just 4% of all insulinomas. Due to the exceedingly uncommon occurrence of these tumors, there is controversy regarding the optimal evidence-based management for these patients. We therefore report on a 70-year-old male patient admitted with 3 months of episodic confusion with concurrent hypoglycemia. The patient was found to have inappropriately elevated endogenous insulin levels during these episodes, and somatostatin-receptor subtype 2 selective imaging revealed a pancreatic mass metastatic to local lymph nodes, spleen, and the liver. Fine needle aspiration of pancreatic and liver lesions confirmed the diagnosis of a low grade pancreatic neuroendocrine tumor. Molecular analysis of tumor tissue revealed a novel mutational profile consistent with pNET. The patient was initiated on octreotide therapy. However, treatment with octreotide alone demonstrated limited efficacy in controlling the patient's symptoms, prompting consideration of other therapies.

68Ga radiolabeled chitosan/curcumin/biotin nanocomposite as a drug carrier and early-stage cancer detection.

Nano chitosan was extracted from shrimp wastes. Biotin, as a tumor-targeting agent, and curcumin, as potential carriers of 68Ga, were immobilized on the nano chitosan, and a novel bio-nanocomposite was designed. It was characterized by FT-IR, SEM, TEM, XRD, TGA, and elemental analysis. It seems that the chitosan has a fibril shape with an average size of 70 nm, and the biotin and curcumin are evenly distributed as obtained SEM images. While, the size of Chit/Cur@Biot bio-nanocomposite was between 10 and 20 nm according to the TEM images. Cell cytotoxicity assay, cellular uptake, and fluorescence spectroscopy on A549 lung cancer cells were performed to show the potential applications of this bio-nanocomposite. The obtained results were demonstrated that Chit/Cur and Chit/Cur@Biot bio-nanocomposite exhibit antitumor activity, while, the Chit/Cur@Biot bio-nanocomposite is more effective than Chit/Cur against cancer cell lines at high concentrations. The results of fluoresce microscopy show that fluoresce of Chit/Cur@Biot was much stronger than Chit/Cur in the A549 cell lines. Moreover, the cellular uptake of Chit/Cur@Biot was enhanced when compared with the control group. The potentials of this bio-nanocomposite as anticancer and cancer-detecting agent in nuclear medicine were confirmed.

Unravelling the role of macrophages in cardiovascular inflammation through imaging: a state-of-the-art review.

Cardiovascular disease remains the leading cause of death and disability for patients across the world. Our understanding of atherosclerosis as a primary cholesterol issue has diversified, with a significant dysregulated inflammatory component that largely remains untreated and continues to drive persistent cardiovascular risk. Macrophages are central to atherosclerotic inflammation, and they exist along a functional spectrum between pro-inflammatory and anti-inflammatory extremes. Recent clinical trials have demonstrated a reduction in major cardiovascular events with some, but not all, anti-inflammatory therapies. The recent addition of colchicine to societal guidelines for the prevention of recurrent cardiovascular events in high-risk patients with chronic coronary syndromes highlights the real-world utility of this class of therapies. A highly targeted approach to modification of interleukin-1-dependent pathways shows promise with several novel agents in development, although excessive immunosuppression and resulting serious infection have proven a barrier to implementation into clinical practice. Current risk stratification tools to identify high-risk patients for secondary prevention are either inadequately robust or prohibitively expensive and invasive. A non-invasive and relatively inexpensive method to identify patients who will benefit most from novel anti-inflammatory therapies is required, a role likely to be fulfilled by functional imaging methods. This review article outlines our current understanding of the inflammatory biology of atherosclerosis, upcoming therapies and recent landmark clinical trials, imaging modalities (both invasive and non-invasive) and the current landscape surrounding functional imaging including through targeted nuclear and nanobody tracer development and their application.

[68Ga]/[90Y]FAPI-46: Automated production and analytical validation of a theranostic pair.

INTRODUCTION: With respect to the broad application of FAPI-46 in therapy and diagnostics, there is a need for an efficient as well as convenient way for routine production and quality control of the theranostic pair [90Y]Y/[68Ga]Ga-FAPI-46, since no monograph is currently available for radiolabelled FAPI derivatives. The aim of the current work is to create a GMP compliant theranostic set up for the production and quality control of the diagnostic [68Ga]Ga-FAPI-46 as well as the therapeutic drug [90 Y]Y-FAPI-46, which can be the basis for future monographic standards. METHODS: Sterile [90Y]yttrium chloride solution and a pharmaceutical grade 68Ge/68Ga generator were applied for the labelling of FAPI-46 using the cassette based synthesis module Trasis EASYONE. All chemicals were GMP-grade and excipients were with marketing authorisation. The quality control included test procedures according to Ph. Eur. RESULTS: Fully automated synthesis of the theranostic pair [90Y]Y/[68Ga]Ga-FAPI-46 was achieved on the Trasis EasyOne synthesizer with a radiochemical yield of 88 ± 7% and 56 ± 5% with a radiochemical purity of >99%. Stability experiments showed a durability for [68Ga]Ga-FAPI-46 within 4 h and for [90Y]Y-FAPI-46 within 24 h. All obtained specifications and validations were compliant with the European Pharmacopoeia and regulatory guidelines. Both products were successfully applied in cancer patients. CONCLUSION: In the present work, efficient and robust procedures for the automated production and quality control of the theranostic pair [68Ga]/[90Y]FAPI 46 were developed and validated using the same synthetic platform. The described methods were evaluated in accordance with existing guidelines and toxicological limits, which can be a valuable basis for future monographic standards.

Role of Ga-68 DOTANOC Positron Emission Tomography/ Computed Tomography Scan in Clinical Management of Patients with Neuroendocrine Tumors and its Correlation with Conventional Imaging- Experience in a Tertiary Care Center in India.

Purpose of Study: Aim of the study was to evaluate the role of 68Gallium-DOTANOC positron emission tomography/computed tomography (68Ga-DOTANOC PET/CT), a pan somatostatin receptor (SSTR) analog in the clinical management of patients with neuroendocrine tumors (NETs) and its correlation with conventional imaging. Materials and Methods: We retrospectively evaluated 69 patients of known/suspected NETs who underwent 68Ga-DOTANOC PET/CT scan for tumor localization (n = 15), stage modification (primary staging, n = 26 and restaging, n = 25) and therapy monitoring (n = 3). We also compared PET scan with conventional imaging as reference standard and evaluated the impact of PET/CT in the clinical management of patients. Results: The concordant findings on 68Ga-DOTANOC PET/CT and conventional imaging seen in 33 and discordant in 36 patients. Among discordant group, disease was upstaged in 32 patients; down staged in 3 patients; no stage change in one patient. PET/CT localized primary tumor in 4 patients. Among patients with raised tumor markers (39/69), PET was positive in 29 and negative in 10 patients. Patients were followed for mean duration of 27 months to assess management. We found strong agreement between positive PET and raised tumor markers (Kappa value = 0.8). Sensitivity and specificity of PET/CT for primary tumor localization, stage modification, and therapy monitoring was >90% (P < 0.05). Conclusions: Study shows that DOTANOC, a broad spectrum SSTRs binding peptide labeled with Ga-68 in PET/CT scan is an excellent modality in the management of NETs patients.

How accurate is 68Gallium-prostate specific membrane antigen positron emission tomography / computed tomography (68Ga-PSMA PET/CT) on primary lymph node staging before radical prostatectomy in intermediate and high risk prostate cancer? A study of patient- and lymph node- based analyses.

BACKGROUND AND AIM: Gallium-68 (68Ga)-Prostate Membrane Specific Antigen Positron Emission Tomography/Computed Tomography (68Ga-PSMA PET/CT) is an emerging diagnostic modality which is gaining importance in individualized prostate cancer (PCa) management era. This study aimed to investigate the diagnostic accuracy of 68Ga-PSMA PET/CT on primary LN staging before radical prostatectomy (RP) in intermediate and high risk PCa. MATERIALS AND METHODS: The retrospectively documented 49 patients with intermediate and high risk non-metastatic PCa who had 68Ga-PSMA PET/CT before RP were enrolled into this study. The histopathology of dissected LNs was used as reference standard to evaluate the accuracy of 68Ga-PSMA PET/CT on primary LN staging, both in per-patient (n = 49) and in per-node (n = 454) analyses. The diagnostic accuracy was investigated using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and by area under the curve (AUC) provided using receiver operating curve (ROC) analysis. RESULTS: Median age was 64 (48-79) years and, median and mean PSA values were 10 (1.31-138) ng/ml and 16.2 (±19.8) ng/ml, respectively. 22 (44.9%) and 27 (55.1%) of patients had intermediate and high risk PCa, respectively. A total of 5 (10.2%) patients had histopathologically proven LN metastasis and 3 (60%) of them was detected in 68Ga-PSMA PET/CT. In per patient analysis, the sensitivity, specifity, PPV and NPV of 68Ga-PSMA PET/CT on primary LN staging were 0.60, 0.96, 0.60 and 0.96, respectively. Among overall 454 LNs, 16 (3.5 %) of them were reported as metastatic in histopathology and, 13 (2.9%) of these metastatic LNs were detected in 68Ga-PSMA PET/CT. In per-node analysis, the sensitivity, specificity, PPV and NPV of 68Ga-PSMA PET/CT on primary LN staging were 0.82, 0.99, 0.87 and 0.99, respectively. The ROC analyses found AUCs for primary LN staging as 0.777 (95%CI:0.508-1.0) in per patient analysis and, as 0.904 (95%CI:0.790 - 1.0) in per node analysis, respectively. CONCLUSION: The use of 68Ga-PSMA PET/CT has promising diagnostic accuracy on primary LN staging before RP in intermediate and high risk PCa. However, the efforts should be taken to increase sensitivity of 68Ga-PSMA PET/CT in individualized treatment era.

Tumor-Induced Osteomalacia Localized and Excised After Pregnancy.

OBJECTIVE: Tumor-induced osteomalacia (TIO) is a rare osteomalacia characterized by paraneoplastic secretion of fibroblast growth factor 23. Concomitant occurrence of TIO during pregnancy is rarer still. Our objective was to report a young patient with debilitating fractures diagnosed with TIO who became pregnant and subsequently had her tumor localized by gallium-68 (Ga-68) DOTATATE positron emission tomography/magnetic resonance imaging (PET/MRI). CASE REPORT: A 28 year-old woman with a 2-year history of stress fractures was found to have the following: (1) alkaline phosphatase level, 220 (reference range, 30-95) U/L; (2) phosphorus level, 2.1 (2.5-5.0) mg/dL; (3) 1,25-dihydroxyvitamin D3 level, <8 (18-72) pg/mL; (4) 24-hour urine phosphorus level, 0.5 (0.3-1.3) g; and (5) fibroblast growth factor 23 levels, 1241 (reference range, <180) RU/mL. The patient became pregnant, and at term, a cesarean delivery was performed. Ga-68 DOTATATE PET/MRI showed a 9-mm intracortical mass in the right fibular head and right femoral and bilateral calcaneal stress fractures. The fibular lesion was resected; pathology showed a 1.5-cm lesion with positive fibroblast growth factor receptor 1 staining. DISCUSSION: This patient with TIO had an uneventful pregnancy and delivery. TIO is typically caused by benign mesenchymal tumors. Ga-68 DOTATATE PET/computed tomography has been used for localizing tumors causing TIO, yet MRI has superior contrast resolution over computed tomography. Therefore, it is not surprising that Ga-68 PET/MRI successfully localized this patient's tumor to the intracortical space of the fibular head and distinguished it from insufficiency fractures. CONCLUSION: To our knowledge, this is the first report of phosphate treatment in a pregnant patient with TIO and the first report of a tumor-inducing TIO being localized by Ga-68 DOTATATE PET/MRI.

68-gallium Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography Detects Rare Testicular Metastasis from Prostate Cancer.

Testicular metastases from solid tumors is a rare entity. We describe one such case where a patient on treatment for prostate cancer presented with a right scrotal swelling. For restaging, whole-body 68-gallium prostate-specific membrane antigen positron emission tomography/computed tomography (PET/CT) was performed. Fused PET/CT images demonstrated intense uptake in the testicular lesion. Unique anatomic and functional information provided by hybrid PET/CT helped in reliably establishing the testicular mass as the site of metastases from prostate cancer, which had a major impact on patient management.

Metastatic Medullary Thyroid Cancer: The Role of 68Gallium-DOTA-Somatostatin Analogue PET/CT and Peptide Receptor Radionuclide Therapy.

CONTEXT: Metastatic medullary thyroid cancer (MTC) is a rare malignancy with minimal treatment options. Many, but not all, MTCs express somatostatin receptors. OBJECTIVE: Our aim was to explore the role of 68Ga-DOTA-somatostatin analogue (SSA) positron emission tomography (PET)/computed tomography (CT) in patients with metastatic MTC and to determine their eligibility for peptide receptor radionuclide therapy (PRRT). METHODS: We retrospectively identified patients with metastatic MTC who had 68Ga-DOTA-SSA PET/CT at 5 centers. We collected characteristics on contrast-enhanced CT, 68Ga-DOTA-SSA and 18F-FDG PET/CT. The efficacy of PRRT was explored in a subgroup of patients. Kaplan-Meier analysis was used to estimate time to treatment failure (TTF) and overall survival (OS). RESULTS: Seventy-one patients were included (10 local recurrence, 61 distant disease). Of the patients with distant disease, 16 (26%) had ≥50% of disease sites with tracer avidity greater than background liver, including 10 (10/61, 16%) with >90%. In 19 patients with contemporaneous contrast-enhanced CT, no disease regions were independently identified on 68Ga-DOTA-SSA PET/CT. Thirty-five patients had an 18F-FDG PET/CT, with 18F-FDG positive/68Ga-DOTA-SSA negative metastases identified in 15 (43%). Twenty-one patients had PRRT with a median TTF of 14 months (95% CI 8-25) and a median OS of 63 months (95% CI 21-not reached). Of the entire cohort, the median OS was 323 months (95% CI 152-not reached). Predictors of poorer OS included a short calcitonin doubling-time (≤24 months), strong 18F-FDG avidity, and age ≥60 years. CONCLUSIONS: The prevalence of high tumor avidity on 68Ga-DOTA-SSA PET/CT is low in the setting of metastatic MTC; nevertheless, PRRT may still be a viable treatment option in select patients.

The Impact of 68Gallium DOTA PET/CT in Managing Patients With Sporadic and Familial Pancreatic Neuroendocrine Tumours.

Objective: Pancreatic neuroendocrine tumours (panNETs) arise sporadically or as part of a genetic predisposition syndrome. CT/MRI, endoscopic ultrasonography and functional imaging using Octreoscan localise and stage disease. This study aimed to evaluate the complementary role of 68Gallium (68Ga)-DOTA PET/CT in managing patients with panNETs. Design: A retrospective study conducted across three tertiary UK NET referral centres. Methods: Demographic, clinical, biochemical, cross-sectional and functional imaging data were collected from patients who had undergone a 68Ga-DOTA PET/CT scan for a suspected panNET. Results: We collected data for 183 patients (97 male): median (SD) age 63 (14.9) years, 89.1 vs. 9.3% (n=163 vs. 17) alive vs. dead (3 data missing), 141 sporadic vs. 42 familial (MEN1, n=36; 85.7%) panNETs. Non-functional vs. functional tumours comprised 73.2 vs. 21.3% (n=134 vs. 39) (10 missing). Histological confirmation was available in 89% of individuals (n=163) but tumour grading (Ki67 classiifcation) was technically possible only in a smaller cohort (n=143): grade 1, 50.3% (n=72); grade 2, 46.2% (n=66) and grade 3, 3.5% (n=5) (40 histopathological classification either not technically feasible or biopsy not perfomed). 60.1% (n=110) were localised, 14.2% (n=26) locally advanced and 23.5% (n=43) metastatic (4 missing). 224 68Ga-DOTA PET/CT scans were performed in total for: diagnosis/staging 40% (n=88), post-operative assessment/clinical surveillance 53% (n=117) and consideration of peptide receptor radionuclide therapy (PRRT) 8% (n=17) (2 missing). PET/CT results confirmed other imaging findings (53%), identified new disease sites (28.5%) and excluded suspected disease (5%). Overall, 68Ga-DOTA PET/CT imaging findings provided additional information in 119 (54%) patients and influenced management in 85 (39%) cases. Conclusion: 68Ga-DOTA PET/CT imaging more accurately stages and guides treatment in patients with sporadic/familial panNETs with newly diagnosed/recurrent disease.

Development and characterization of two novel 68 Ga-labelled neuropeptide Y short analogues with potential application in breast cancer imaging.

In vivo receptor targeting with radiolabelled peptide-based probes is an attractive approach for the development of novel radiotracers for molecular imaging. This work presents the development and characterization of two novel neuropeptide Y analogues labelled with a positron emitter 68 Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatized with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). In both cases, a single product with radiochemical purity higher than 95% was obtained. The two complexes were hydrophilic, showed remarkable in vitro stability, good cellular uptake, binding affinity in the nanomolar range and high cellular internalization rate. Biodistribution studies revealed low blood uptake and elimination through the urinary tract. The addition of an acetyl group in the spacer increased the lipophilicity of C2 and modified the reactivity of the ε-amino group of the lysine which resulted in lower protein binding and lower percentage of injected dose in bladder and urine. The tumour versus muscle ratio was (3.8 ± 0.4) for 68 Ga-L1 and (4.7 ± 0.4) for 68 Ga-L2. These results encourage performing further studies in order to complete the evaluation of both tracers as potential radiopharmaceutical for breast cancer imaging.

False-Positive Gallium-68 DOTATATE PET/CT in Vertebral Hemangioma.

A healthy 52-year-old man started to have few minutes spells of palpitation, tachycardia, hot flashes, and chest tightness. He had a lab work-up for carcinoid, including 5-hydroxyindoleacetic acid (5-HIAA), which was negative. Months later, his symptoms became worse which warranted further investigation to exclude carcinoid disease. Gallium-68 DOTATATE positron emission tomography combined with computed tomography (PET/CT) scanning was performed to assess the patient for carcinoid tumor. It showed foci of radiotracer avidity in the thoracic and lumber spine. Magnetic resonance imaging (MRI) for the vertebral lesions showed atypical hemangioma. Subsequently, follow-up serum chromogranin A testing was negative.