Search Results (67)

Background/Objectives: The gastrin-releasing peptide receptor (GRPR) shows high-density expression in prostate cancer (PCa), especially in the early stages of the disease. The introduction of a safe radiotracer for assessing GRPR-expression in PCa may serve as an alternative or complementary tracer to PSMA-directed probes for patients with insufficient PSMA expression. In the present study, the tolerability and safety, biodistribution, and dosimetry of the new GRPR-targeting radiopeptide [^99mTc]Tc-DB8 were investigated for the first time in male PCa patients. A mass escalation study was performed, aiming to improve tumor-to-background contrast and, thereby, to enhance diagnostic accuracy. Methods: Sixteen male patients were enrolled in a single-center diagnostic open-label exploratory Phase I clinical trial. Patients were administered a single intravenous injection of 40, 80, or 120 µg of [^99mTc]Tc-DB8 peptide (n = 5–6) and underwent whole-body planar imaging (anterior and posterior) 2, 4, 6, and 24 h post-injection (pi) and SPECT-CT acquisition 2, 4, and 6 h pi. Results: Administration of [^99mTc]Tc-DB8 was well tolerated at all tested peptide masses. The effective dose did not differ significantly between the injected peptide mass and was 0.005 ± 0.003 mSv/MBq. High activity uptake was observed in the pancreas and kidneys, which 3-fold decreased with an increasing injected peptide mass from 40 to 120 µg. The activity uptake in primary tumors did not differ significantly between cohorts injected with different peptide masses [SUV_max 1.65–9.96]. The tumor-to-muscle ratios increased with time and were the highest for the cohort injected with 120 µg of peptide, 7.2 ± 3.1 (4.64-11-25) at 4 h pi. Conclusions: Single intravenous administration of [^99mTc]Tc-DB8, for visualization of GRPR expression in PCa using SPECT imaging was well tolerated in a peptide mass range of 40–120 µg. An injected peptide mass of 80–120 µg/patient and SPECT acquisition 2–4 h pi were found to be optimal for further clinical studies due to the significantly lower activity accumulation in the pancreas and kidneys. Full article

Drug–radiopharmaceutical interactions can significantly alter radiotracer biodistribution, complicating diagnostic accuracy. This case report describes a 64-year-old male who underwent a Technetium-99m-methoxyisobutyl isonitrile (^99mTc-MIBI) parathyroid scan for suspected primary hyperparathyroidism. Initially, the patient was asked to discontinue his medications for his chronic illnesses for 24 h prior to the scan. However, the images revealed significantly reduced counts/tracer uptake in the thyroid, parathyroid and cardiac tissues in both the early and delayed phases. After a detailed review of his medication profile, it was postulated that there were potential interactions involving multiple P-glycoprotein (P-gp) substrates with specific emphasis on amlodipine, atorvastatin and telmisartan. The patient was advised to discontinue all medications for 72 h prior to the date of a repeat scan which was scheduled for two weeks after his initial scan. The repeat scan successfully detected a small focus of marked tracer retention in the left inferior parathyroid bed, suggestive of a small parathyroid adenoma. Post-surgery, the focus identified on the scan was removed and histologically confirmed to be a parathyroid adenoma. This is the first report of its kind among nuclear medicine patients in Jamaica. It highlights the importance of reviewing medication history prior to nuclear imaging, particularly when using radiotracers affected by P-gp mechanisms. This is crucial for mitigating against false-negative results, thus ensuring accurate diagnosis and appropriate clinical management. Full article

Background/Objectives: In a previous study, we observed significantly prolonged hepatic and pulmonary first-pass transit times (TTs) for ^99mTc-pertechnetate absorbed through the colorectal mucosa during per-rectal portal scintigraphy (PRPS). This decrease in radiotracer flow velocity was not seen when ^99mTc-pertechnetate was administered into the spleen during trans-splenic portal scintigraphy or injected intravenously in radionuclide angiocardiography. We hypothesized that ^99mTc-pertechnetate, an artificial compound, is recognized during colorectal absorption as a potentially hazardous chemical (PHC), with its hepatic and pulmonary slowdown aiding elimination. A similar sudden decrease in portal flow occurs during early metastasis of colorectal cancer (CRC), as shown by a pathological rise in the hepatic perfusion index. We aimed to study the hepatic and pulmonary vasoactive responses triggered by PHCs after they pass through the gut mucosa and evaluate the potential activation of this mechanism in early CRC metastasis. Methods: We measured transit times to determine whether hepatic and pulmonary vasoconstriction occur in response to radiotracers administered at different sites. We performed PRPS with in vivo ^99mTc-labelled RBC to evaluate the liver transit time (LTT) and right heart to liver circulation time (RHLT). Liver angioscintigraphy (LAS) was used to assess RHLT following the intravenous injection of ^99mTc-pertechnetate and ^99mTc-HDP (hydroxyethylene-diphosphate). Lower rectum transmucosal dynamic scintigraphy (LR-TMDS) was conducted to measure RHLT of ^99mTc-pertechnetate delivered into the lower rectum submucosa. LAS was performed to assess LTT for ^99mTc-HDP intravenously injected and delivered to the gut mucosa via arterial flow. Results: In healthy volunteers, PRPS showed notably increased LTT, ranging from 23.5 to 25.5 s, and RHLT (between 39.5 and 42.5 s) for in vivo ^99mTc-labelled RBC. Significantly lower RHLT values ranging from 9 to 13.5 were observed for ^99mTc-pertechnetate and ^99mTc-HDP administered intravenously during LAS, as well as for ^99mTc-pertechnetate at LR–TMDS (between 12 and 15 s). The LTT assessed at LAS for ^99mTc-HDP ranged from 22 to 27 s. Conclusions: An intense vasoconstriction occurs in the liver and lungs in response to substances recognized by the body as PHCs when they pass through the gut mucosa, aiding their elimination. Full article

Urologic oncological surgery increasingly makes use of robotic systems to realize precise and minimally invasive resections, convent to shorter hospital stays and faster recovery times. The dexterity gains enabled through procedures such as robot-assisted (RA) prostatectomy have helped realize significant advancements in recent years. Complementing these effects via the used of hybrid tracers that illuminate surgical targets, i.e., cancerous tissue, has helped advance the surgical decision making via enhanced visualization. A well-known example is Indocyanine green (ICG)-Technetium-99m (^99mTc)-nanocolloid, a hybrid extension of the radiopharmaceutical ^99mTc-nanocolloid. These hybrid tracers provide a direct link between preoperative imaging roadmaps and intraoperative target identification, and improve efficiency, accuracy, and confidence of the urologist in procedures such as sentinel lymph node biopsy (SLNB). Receptor-targeted hybrid tracer analogues, for e.g., prostate specific membrane antigen (PSMA), are also being explored as an extension of the ongoing efforts that use radiotracers such as ^99mTc-PSMA-I&S. Together, these efforts jointly pave the way for novel techniques in intraoperative lesion localization in other urological malignancies. This narrative review discusses the potential use of hybrid tracers in robotic oncological urology, including different imaging techniques and their applications for tumor localization for prostate, bladder, and kidney cancer. Full article

Shedding light on Hidradenitis Suppurativa activity: a pilot study to evaluate the potential of [^99mTc]Tc-anti-TNF-alpha scintigraphy. Background/Objectives: Hidradenitis suppurativa (HS), also known as acne inversa and Verneuil’s disease, is a chronic and non-contagious auto-inflammatory disease of pilo-sebaceous units that can lead to severe complications and sequelae. The actual prevalence of HS is unknown due to diagnostic delay and/or misdiagnosis, but it is estimated to affect 0.00033–4.1% of the general population worldwide. Only severe cases are referred for imaging assessment, and the final diagnosis is mostly established on a clinical basis. Here, we present a pilot study aiming to evaluate clinically active inflammatory disease in patients with HS using [^99mTc]Tc-anti-TNF-alpha scintigraphy. Methods: Four patients (2 male, 2 female) had their HS clinical features measured through the HS-PGA and Hurley Score and compared to [^99mTc]Tc-anti-TNF-alpha scintigraphy findings. Results: Scintigraphy with [^99mTc]Tc-anti-TNF-alpha showed abnormal uptake in clinically active lesions of HS and also detected some clinically unknown potential active lesions, later confirmed by clinical reassessment after the imaging. Conclusions: Our results suggest that scintigraphy with [^99mTc]Tc-anti-TNF-alpha may be able to detect increased radiotracer uptake in most clinically identified active lesions in this pilot cohort. While promising, due to the inherent limitations of this pilot study, more studies need to be carried out to arrive at a definitive diagnostic assessment of active inflammatory disease using this method. Full article

Background/Objectives: The extensive use of computed tomography (CT) has led to a significant increase in the detection of small and non-palpable pulmonary nodules, necessitating the use of invasive methods for definitive diagnosis. Video-assisted thoracoscopic surgery (VATS) has become the preferred procedure for nodule resections; however, intraoperative localization remains challenging, especially for deep or subsolid lesions. This study explores whether SPECT/CT improves the technical and clinical outcomes of radio-guided occult lesion localization (ROLL) before uniportal video-assisted thoracoscopic surgery (u-VATS). Methods: This is a retrospective study involving consecutive patients referred for the resection of pulmonary nodules who underwent CT-guided ROLL followed by u-VATS between September 2017 and December 2024. From January 2023, SPECT/CT was systematically added after planar imaging. The cohort was divided into a planar group and a planar + SPECT/CT group. The inclusion criteria involved nodules sized ≤ 2 cm, with ground glass or solid characteristics, located at a depth of <6 cm from the pleural surface. ^99mTc-MAA injected activity, timing, the classification of planar and SPECT/CT image findings (focal uptake, multisite with focal uptake, multisite without focal uptake), spillage, and post-procedure complications were evaluated. Statistical analysis was performed, with continuous data expressed as the median and categorical data as the number. Comparisons were made using chi-square tests for categorical variables and the Mann–Whitney U test for procedural duration. Cohen’s kappa coefficient was calculated to assess agreement between imaging modalities. Results: In total, 125 patients were selected for CT-guided radiotracer injection followed by uniportal-VATS. The planar group and planar + SPECT/CT group comprised 60 and 65 patients, respectively. Focal uptake was detected in 68 (54%), multisite with focal uptake in 46 (36.8%), and multisite without focal uptake in 11 patients (8.8%). In comparative analyses between planar and SPECT/CT imaging in 65 patients, 91% exhibited focal uptake, revealing significant differences in classification for 40% of the patients. SPECT/CT corrected the classification of 23 patients initially categorized as multisite with focal uptake to focal uptake, improving localization accuracy. The mean procedure duration was 39 min with SPECT/CT. Pneumothorax was more frequently detected with SPECT/CT (43% vs. 1.6%). The intraoperative localization success rate was 96%. Conclusions: SPECT/CT imaging in the ROLL procedure for detecting pulmonary nodules before u-VATs demonstrates a significant advantage in reclassifying radiotracer positioning compared to planar imaging. Considering its limited impact on surgical success rates and additional procedural time, SPECT/CT should be reserved for technically challenging cases. Larger sample sizes, multicentric and prospective randomized studies, and formal cost–utility analyses are warranted. Full article

Background/Objectives: Radiolabeled biomolecules specifically targeting overexpressed structures on tumor cells hold great potential for prostate cancer (PCa) imaging and therapy. Due to heterogeneous target expression, single radiopharmaceuticals may not detect or treat all lesions, while simultaneously applying two or more radiotracers potentially improves staging, stratification, and therapy of cancer patients. This study explores a dual-tracer SPECT approach using [¹¹¹In]In-RM2 (targeting the gastrin-releasing peptide receptor, GRPR) and [^99mTc]Tc-PSMA-I&S (targeting the prostate-specific membrane antigen, PSMA) as a proof of concept. To mimic heterogeneous tumor lesions in the same individual, we aimed to establish a dual xenograft mouse model for preclinical evaluation. Methods: CHO-K1 cells underwent lentiviral transduction for human GRPR or human PSMA overexpression. Six-to-eight-week-old female immunodeficient mice (NOD SCID) were subsequently inoculated with transduced CHO-K1 cells in both flanks, enabling a dual xenograft with similar target density and growth of both xenografts. Respective dual-isotope imaging and γ-counting protocols were established. Target expression was analyzed ex vivo by Western blotting. Results: In vitro studies showed similar target-specific binding and internalization of [¹¹¹In]In-RM2 and [^99mTc]Tc-PSMA-I&S in transduced CHO-K1 cells compared to reference lines PC-3 and LNCaP. However, in vivo imaging showed negligible tumor uptake in xenografts of the transduced cell lines. Ex vivo analysis indicated a loss of the respective biomarkers in the xenografts. Conclusions: Although the technical feasibility of a dual-tracer SPECT imaging approach using ¹¹¹In and ^99mTc has been demonstrated, the potential of [^99mTc]Tc-PSMA-I&S and [¹¹¹In]In-RM2 in a dual-tracer cocktail to improve PCa diagnosis could not be verified. The animal model, and in particular the transduced cell lines developed exclusively for this project, proved to be unsuitable for this purpose. The in/ex vivo experiments indicated that results from an in vitro model may not necessarily be successfully transferred to an in vivo setting. To assess the potential of this dual-tracer concept to improve PCa diagnosis, optimized in vivo models are needed. Nevertheless, our strategies address key challenges in dual-tracer applications, aiming to optimize future SPECT imaging approaches. Full article

Background: ¹⁸F-NaF and ^99mTc-MDP are widely used bone imaging tracers, but their comparative uptake in bone versus cartilage is unclear. This study aimed to directly compare these patterns in rats to guide musculoskeletal molecular imaging. Methods: Male Sprague-Dawley rats underwent in vivo and ex vivo radiotracer studies. Tracer uptake (%ID/g) was quantified in bone and cartilage at 30, 60, or 120 min post-injection (¹⁸F-NaF or ^99mTc-MDP), and across different ages. Additional rats received subcutaneous implants of viable or devitalized bone and cartilage; uptake was assessed using PET/CT, autoradiography, and histology. Results: ¹⁸F-NaF showed faster blood/background clearance and higher target-to-background ratios compared to ^99mTc-MDP, especially in weight-bearing joint cartilage. ¹⁸F-NaF uptake in cancellous bone significantly exceeded that of ^99mTc-MDP, whereas ^99mTc-MDP showed higher uptake in knee cartilage. Age-related analysis showed maximal knee cartilage accumulation in aged rats. Histological and cell inactivation studies confirmed that ¹⁸F-NaF uptake reflects both cellular activity and degree of calcification. Conclusions:¹⁸F-NaF demonstrates distinctive, quantifiable uptake in cartilage, dependent on both cellular activity and calcification, and exhibits favorable imaging characteristics versus ^99mTc-MDP for cartilage metabolism. These findings support ¹⁸F-NaF as a promising tool for early diagnosis and therapeutic monitoring of bone and joint disorders, and provide pathophysiological insight into the dynamics of the bone–cartilage interface. Full article

A 30-year-old woman presented with progressive edema and mild diarrhea. Laboratory examination revealed hypoalbuminemia. She underwent ^99mTc-antimony sulphide colloid (^99mTc-ASC) lymphoscintigraphy to evaluate potential loss of protein through gastrointestinal tract caused by lymphatic leakage and detect abnormalities in the lymphatic systems. The images showed abnormal leakage of radiotracers in the bowel, suggestive of protein loss through the gastrointestinal tract. Abnormal visualization of the lower part of thoracic duct and bilateral venous angle was also demonstrated on ^99mTc-ASC scintigraphy. It suggested secondary intestinal lymphangiectasis caused by lymphatic obstruction and reflux. Enhanced CT reconstruction of the small intestine revealed roughness and thickening of intestinal wall, consistent with the diagnosis of protein-losing enteropathy. Full article

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. Full article

Athletes with heart disease are at increased risk of malignant ventricular arrhythmias and sudden cardiac death compared to their sedentary counterparts. When athletes have symptoms or abnormal findings at preparticipation screenings, a precise diagnosis by differentiating physiological features of the athlete’s heart from pathological signs of cardiac disease is as important as it is challenging. While traditional imaging methods such as echocardiography, cardiac magnetic resonance, and computed tomography are commonly employed, nuclear medicine offers unique advantages, especially in scenarios requiring stress-based functional evaluation. This article reviews the use of nuclear medicine techniques in the diagnostic work-up of athletes with suspected cardiac diseases by highlighting their ability to investigate myocardial perfusion, metabolism, and innervation. The article discusses the application of single photon emission computed tomography (SPECT) and positron emission tomography (PET) using radiotracers such as [99mTc]MIBI, [99mTc]HDP, [18F]FDG, and [123I]MIBG. Several clinical scenarios are explored, including athletes with coronary atherosclerosis, congenital coronary anomalies, ventricular arrhythmias, and non-ischemic myocardial scars. Radiation concerns are addressed, highlighting that modern SPECT and PET equipment significantly reduces radiation doses, making these techniques safer for young athletes. We conclude that, despite being underutilized, nuclear medicine provides unique opportunities for accurate diagnosis and effective management of cardiac diseases in athletes. Full article

Background: The concept of radiotheranostics relies on the overexpression of a biomolecular target on malignant cells to direct diagnostic/therapeutic radionuclide-carriers specifically to cancer lesions. The concomitant expression of more than one target in pathological lesions may be elegantly exploited to improve diagnostic sensitivity and therapeutic efficacy. Toward this goal, we explored a first example of a combined application of [^99mTc]Tc-DT11 (DT11, N₄-Lys(MPBA-PEG4)-Arg-Arg-Pro-Tyr-Ile-Leu-OH; NTS₁R-specific) and [^99mTc]Tc-DB7(DB7, N₄-PEG2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt; GRPR-specific) in prostate cancer models. Methods: Accordingly, the behavior of [^99mTc]Tc-DT11 was compared with that of the [^99mTc]Tc-DT11+[^99mTc]Tc-DB7 mixture in prostate adenocarcinoma PC-3 cells and xenografts in mice. The impact of stabilizing both radiotracers by Entresto^®, as a source of the potent neprilysin inhibitor sacubitrilat, was also investigated. Results: The PC-3 cell binding of the [^99mTc]Tc-DT11+[^99mTc]Tc-DB7 mixture surpassed that of [^99mTc]Tc-DT11. Likewise, the PC-3 tumor uptake of the [^99mTc]Tc-DT11+[^99mTc]Tc-DB7 mixture at 4 h post-injection was superior (7.70 ± 0.89%IA/g) compared with [^99mTc]Tc-DT11 (4.23 ± 0.58%IA/g; p < 0.0001). Treatment with Entresto^® led to further enhancement of the tumor uptake (to 11.57 ± 1.92%IA/g; p < 0.0001). Conclusions: In conclusion, this first preclinical study on prostate cancer models revealed clear advantages of dual NTS₁R/GRPR targeting, justifying further assessment of this promising concept in other cancer models. Full article

With the development of PD-1/PD-L1 immune checkpoint inhibitor therapy, the ability to monitor PD-L1 expression in the tumor microenvironment is important for guiding therapy. This study was performed to develop a novel radiotracer with optimal pharmacokinetic properties to reflect PD-L1 expression in vivo via single-photon emission computed tomography (SPECT) imaging. [^99mTc]Tc-HYNIC-WL12-tricine/M (M = TPPTS, PDA, ISONIC, 4-PSA) complexes with high radiochemical purity (>97%) and suitable molar activity (from 100.5 GBq/μmol to 300 GBq/μmol) were prepared through a kit preparation process. All ^99mTc-labeled HYNIC-WL12 radiotracers displayed good in vitro stability for 4 h. The affinity and specificity of the four radiotracers for PD-L1 were demonstrated both in vitro and in vivo. The results of biodistribution studies displayed that the pharmacokinetics of the ^99mTc-HYNIC-conjugated radiotracers were significantly influenced by the coligands of the radiotracers. Among them, [^99mTc]Tc-HYNIC-WL12-tricine/ISONIC exhibited the optimal pharmacokinetic properties (t_1/2α = 8.55 min, t_1/2β = 54.05 min), including the fastest clearance in nontarget tissues, highest tumor-to-background contrast (e.g., tumor-to-muscle ratio, tumor-to-blood ratio: 40.42 ± 1.59, 14.72 ± 2.77 at 4 h p.i., respectively), and the lowest estimated radiation absorbed dose, highlighting its potential as a clinical SPECT imaging probe for tumor PD-L1 detection. Full article

Background: Technology allows us to predict a histopathological diagnosis, but the high costs prevent the large-scale use of these possibilities. The current liberal indication for surgery in benign thyroid conditions led to a rising frequency of incidental thyroid carcinoma, especially low-risk papillary micro-carcinomas. Methods: We selected a cohort of 148 patients with thyroid nodules by ultrasound characteristics and investigated them by fine needle aspiration cytology (FNAC)and prospective BRAF collection for 70 patients. Also, we selected 44 patients with thyroid nodules using semi-quantitative functional imaging with an oncological, ^99mTc-methoxy-isobutyl-isonitrile (^99mTc-MIBI) radiotracer. Results: Following a correlation with final histopathological reports in patients who underwent thyroidectomy, we introduced the results in a machine learning program (AI) in order to obtain a pattern. For semi-quantitative functional visual pattern imaging, we found a sensitivity of 33%, a specificity of 66.67%, an accuracy of 60% and a negative predicting value (NPV) of 88.6%. For the wash-out index (WOind), we found a sensitivity of 57.14%, a specificity of 50%, an accuracy of 70% and an NPV of 90.06%.The results of BRAF in FNAC included 87.50% sensitivity, 75.00% specificity, 83.33% accuracy, 75.00% NPV and 87.50% PPV. The prevalence of malignancy in our small cohort was 11.4%. Conclusions: We intend to continue combining preoperative investigations such as molecular detection in FNAC, ^99mTc-MIBI scanning and AI training with the obtained results on a larger cohort. The combination of these investigations may generate an efficient and cost-effective diagnostic tool, but confirmation of the results on a larger scale is necessary. Full article

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. Full article