Introduction: Thyroid cancer is the main endocrine neoplasia worldwide, for which ¹³¹I therapy is the cornerstone treatment. One of the main problems of follow up in patients with this type of cancer, is the need for thyroglobulin stimulation, not to mention the poor availability of ¹²³I or ¹²⁴I, to perform studies with a higher degree of sensitivity. Prostatic Specific Membrane Antigen (PSMA) PET/CT has demonstrated to be quite useful in a diversified number of neoplasms, on behalf of its capacity of evaluating the extent of type II carboxypeptidase expression in vascular endothelium. The end point of this article is to assess whether this novel image method possesses applicability in thyroid neoplasms follow up, for diagnostic and potentially therapeutic purposes.Methods: We retrospectively evaluated well differentiated metastatic thyroid cancer patients, who underwent a post therapeutic ¹³¹I dose whole body scan (WBS) and complementary SPECT/CT, as well as ⁶⁸Ga-PSMA–11 PET/CT.Results: Ten patients with differentiated thyroid cancer were included, of whom 80% were women and 20% men, mean age was 58 years old (± 11.6). Sixty-four metastatic lesions were analyzed, 67.19% had papillary histology and 32.81% were follicular type, the most affected site of metastases was bone in 57.81%, followed by lung 17.19%, lymph nodes 7.81%, postoperative thyroid bed 4.69%, brain 4.69% and others 7.81%. ⁶⁸Ga PSMA-11 PET/CT detected 64/64 lesions, all of them also identified by computed tomography (CT), whereas ¹³¹I SPECT/CT detected 55/64 lesions. Discrepant lesions were localized in lung 44.4%, brain 22.2%, postoperative thyroid bed 11.1%, lymph nodes 11.1% and bone 11.1%. The degree of correspondence among observers was outstanding for both radiotracers, but close upon perfect for PSMA-11 (κ = 0.98; 95% CI, 0.80 – 0.91), as opposed to ¹³¹ I (κ = 0.86; 95% CI, 0.71 – 0.76).Conclusions: ⁶⁸Ga-PSMA PET/CT showed an utterly superior capability for metastatic lesion detection when compared to ¹³¹I SPECT/CT. These findings suggest that PSMA PET/CT could possibly and precociously identify radioiodine refractoriness. PSMA uptake values not only expedite diagnosis, but also award it the ability to be used for therapeutic intents.

Neuroendocrine differentiation of prostate cancer (NEDPC) includes de novo presentation and secondary to epigenetic changes, referred as therapy-induced neuroendocrine prostate cancer (t-NEPC). Molecular imaging with prostate-specific membrane antigen (PSMA) and somatostatin analogues positron emission tomography (PET/CT) in NEDPC have not been validated. ¹⁸F-FDG (fluorodeoxyglucose) PET/CT has numerous limitations in prostate cancer (PCa) and the utility in NEDPC has only been reported in a few series of cases. The objective of this study is to compare the lesions detection rate of the three radiotracers in metastatic t-NEPC patients. (1) Material and Methods: Retrospective evaluation of patients with prostate adenocarcinoma treated with androgen deprivation therapy, chemotherapy, a novel androgen receptor pathway inhibitor or a combination of them and a second tumour biopsy confirming t-NEPC was made. All patients underwent ¹⁸F PSMA-1007, ¹⁸F AlF-NOTA-Octreotide, and ¹⁸F-FDG PET/CT. Evaluation of positive lesions was determined and SUVmax of each radiotracer was estimated and correlated with computer tomography (CT) findings. (2) Results: A total of eight patients were included. The mean time from diagnosis of prostate adenocarcinoma to t-NEPC was 28.2 months, with a mean serum specific prostate antigen (PSA) of 16.6 ng/dl at the time of NEPC diagnosis. All patients were treated with antiandrogen therapy and 87.5% with chemotherapy. A total of 273 lesions were identified by CT from which 182 were detected by ¹⁸F-FDG PET/CT, 174 lesions by ¹⁸F PSMA-1007, and 59 by ¹⁸F AlF-NOTA-Octreotide. An interpatient analysis of the lesions was performed and dual tracer ¹⁸F-FDG PET/CT and ¹⁸F PSMA-1007 PET/CT detected a total of 270/273 lesions (98.9%). (3) Conclusions: NEDPC patients demonstrated wide inter and intrapatient molecular imaging heterogeneity within the three radiotracers. ¹⁸F-FDG detected most lesions in t-NEPC among all radiotracers, especially in visceral sites; ¹⁸F PSMA-1007 detected more bone lesions. ¹⁸F AlF-NOTA-Octreotide showed no significant utility.

Prostate cancer is a leading cause of cancer death in men worldwide. Imaging plays a key role in disease detection and initial staging. Emerging data has shown the superiority of PSMA imaging with PET/CT over conventional imaging for primary diagnoses. Single photon emission computed tomography is more available worldwide, and the imaging agent is low in cost. The aim of this study is to compare the diagnostic accuracy of ^99mTc-EDDA/HYNIC-iPSMA SPECT/CT to ¹⁸F-PSMA-1007 PET/CT in the primary diagnosis of prostate cancer and the impact on clinical staging. Methods: In this prospective controlled study, 18 patients with histologically confirmed prostate cancer with unfavorable intermediate-, high-, and very high-risk characteristics were recruited to undergo ¹⁸F-PSMA-PET/CT and ^99mTc-iPSMA SPECT/CT. The median age of the patients was 71 years old, and the median PSA level was 23.3 ng/mL. Lesions were divided into the prostate, seminal vesicles, lymph nodes, bone, and visceral metastases. Volumetric analysis was also performed between the two imaging modalities and correlated with PSA levels. Results: A total of 257 lesions were detected on ¹⁸F-PSMA-PET/CT: prostate (n = 18), seminal vesicles (n = 12), locoregional lymph nodes (n = 62), non-locoregional (n = 67), bone (n = 90), and visceral (n = 8). Of these, ^99mTc-iPSMA-SPECT/CT detected 229 lesions, while both reviewers detected 100% of the lesions in the prostate (18/18), seminal vesicles (12/12), and visceral (8/8); LN LR (56/62; 90%), NLR (57/67; 85%), and bone (78/90; 86%). There were no statistically significant differences between volumetric parameters (t = −0.02122; p = 0.491596). Conclusions: ^99mTc-iPSMA SPECT/CT is useful in the primary diagnosis of prostate cancer. Despite it showing a slightly lower lesion detection rate compared to ¹⁸F-PSMA PET/CT, it exhibited no impact on clinical staging and, consequently, the initial treatment intention.

Background/Objectives: Prostate cancer (PC) represents the second most diagnosed form of cancer in men on a global scale. Despite the theranostic efficacy of prostate-specific membrane antigen (PSMA) radioligands, there is a spectrum of PC disease in which PSMA expression is low or absent. The gastrin-releasing peptide receptor (GRPR), also known as the bombesin type 2 receptor, has been identified as a target in both the early and advanced stages of PC. The objective of this study was to prepare and preclinically evaluate [^99mTc]Tc-iPSMA-Bombesin ([^99mTc]Tc-iPSMA-BN), estimate dosimetry in healthy subjects, and assess the diagnostic efficacy of the radiotracer in patients with metastatic PC, with the hypothesis of non-inferiority to one of the gold standards, [¹⁸F]-PSMA-1007. Moreover, the potential of [^99mTc]Tc-iPSMA-BN as a theranostic pair with [¹⁷⁷Lu]Lu-iPSMA-BN was investigated. Methods: [^99mTc]Tc-iPSMA-BN was prepared under GMP conditions with radiochemical purities > 95%, showing specific recognition by PSMA and GRP receptors in prostate cancer cells and mice bearing PC tumors. Six healthy volunteers were enrolled, and [^99mTc]Tc-iPSMA-BN SPECT/CT imaging (740 MBq) was performed to estimate the dosimetry. The pilot clinical study included seven mCRPC and four mCSPC patients with prior androgen deprivation therapy. All patients had a recent [¹⁸F]-PSMA-PET/CT scan and were enrolled in this prospective study on their own signed behalf. Volumetric lesion target-to-background ratios (TBRs) were obtained from PET/CT and SPECT/CT images. Results: [^99mTc]Tc-iPSMA-BN effective radiation dose was 1.94 ± 0.39 mSv/740 MBq. A total of 178 lesions were detected via CT, 162 via [¹⁸F]-PSMA-1007 PET, and 155 via [^99mTc]Tc-iPSMA-BN SPECT. Three patients with mCRPC had higher TBR values on SPECT than on PET. [^99mTc]Tc-iPSMA-BN appears to have better lesion detection in patients with aggressive histologic transformation. Two-way ANOVA analysis revealed a significant difference in TBR values between patients with mCRPC and mCSPC (p < 0.05) but no difference between [¹⁸F]-PSMA-1007 and [^99mTc]Tc-iPSMA-BN (p > 0.05). In one patient, [¹⁷⁷Lu]Lu-iPSMA-BN showed a high correlation with [^99mTc]Tc-iPSMA-BN for lesions that concentrated radioactivity. Conclusions: [^99mTc]Tc-iPSMA-BN SPECT/CT is a promising alternative not only for diagnostic purposes but also for broadening the spectrum of PC patients who may benefit from radionuclide theranostics. The results justify the development of a clinical trial involving a significant number of patients with PC.

Recently, we reported a new fibroblast activation protein (FAP) inhibitor radiopharmaceutical based on the ^99mTc-((R)-1-((6-hydrazinylnicotinoyl)-D-alanyl) pyrrolidin-2-yl) boronic acid (^99mTc-HYNIC-D-Alanine-BoroPro)(^99mTc-HYNIC-iFAP) structure for tumor microenvironment SPECT imaging. This research aimed to synthesize ⁶⁸Ga-[2,2′,2″,2‴-(2-(4-(2-(5-(((S)-1-((S)-2-boronopyrrolidin-1-yl)-1-oxopropan-2-yl)carbamoyl)pyridin-2-yl)hydrazine-1-carbothioamido)benzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid] (⁶⁸Ga-DOTA-D-Alanine-BoroPro)(⁶⁸Ga-iFAP) as a novel radiotracer for PET imaging and evaluate its usefulness for FAP expression in malignant and non-malignant tissues. The coupling of p-SCN-benzene DOTA with HYNIC-iFAP was used for the chemical synthesis and further labeling with ⁶⁸Ga. Radiochemical purity was verified by radio-HPLC. The specificity of ⁶⁸Ga-iFAP was evaluated in HCT116 cells, in which FAP expression was verified by immunofluorescence and Western blot. Biodistribution and biokinetic studies were performed in murine models. ⁶⁸Ga-iFAP uptake at the myocardial level was assessed in mice with induced infarction. First-in-human images of ⁶⁸Ga-iFAP in healthy subjects and patients with myocardial infarction, glioblastoma, prostate cancer, and breast cancer were also obtained. DOTA-D-Alanine BoroPro was prepared with a chemical purity of 98% and was characterized by UPLC mass spectroscopy, FT-IR, and UV-vis. The ⁶⁸Ga-iFAP was obtained with a radiochemical purity of >95%. In vitro and in vivo studies demonstrated ⁶⁸Ga-iFAP-specific recognition for FAP, rapid renal elimination, and adequate visualization of the glioblastoma, breast tumor, prostate cancer, and myocardial infarction sites. The results of this research justify further dosimetry and clinical trials to establish the specificity and sensitivity of ⁶⁸Ga-iFAP PET for FAP expression imaging.

IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory condition that can mimic malignancy due to its tumorous lesions. Marginal zone lymphoma (MZL), a low-grade B cell lymphoma, may occasionally arise in the context of chronic immune stimulation. The synchronous occurrence of IgG4-RD and MZL is rare and diagnostically challenging. We report the case of a 39-year-old male with right hemiplegia and aphasia, initially suspected to have a meningioma based on magnetic resonance imaging (MRI) findings. Histopathology following surgical resection revealed features consistent with IgG4-RD. Subsequently, [¹⁸F]-FDG PET/CT ([¹⁸F]-fluorodeoxyglucose positron emission tomography/computed tomography) demonstrated a metabolically inactive extra-axial supratentorial lesion, as well as a hypermetabolic triangular consolidation in the left lower lung lobe. Lung biopsy confirmed bronchus-associated lymphoid tissue MZL. Immunohistochemistry supported the dual diagnosis. Complementary 99mTc-iFAP SPECT/CT (single photon emission computed tomography/CT) demonstrated focal uptake in the central nervous system lesion but not in the pulmonary lesion. Multimodal image fusion with brain MRI facilitated precise anatomical and functional correlation. The coexistence of IgG4-RD and MZL raises important considerations regarding shared immunopathogenic mechanisms. Dual molecular imaging with FDG and FAPI (fibroblast activating protein inhibitor)-based radiotracers proved essential in discriminating between inflammatory and neoplastic components of disease, enabling accurate diagnosis and guiding appropriate management. This case highlights the value of [¹⁸F]-FDG PET/CT and 99mTc-iFAP SPECT/CT in the evaluation of complex systemic diseases. fibroblast activation protein–targeted imaging may play a key role in the diagnostic workup of IgG4-RD and in distinguishing it from coexisting lymphoproliferative disorders. Article published online: 31 July 2025 © 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India