Tuberculosis (TB) remains a leading infectious cause of morbidity and mortality worldwide, and major diagnostic and therapeutic challenges persist despite advances in microbiologic and molecular testing. Over the past decade, molecular imaging, especially with FDG PET/CT, has transformed our understanding of TB pathogenesis, the spectrum of early and subclinical disease, mechanisms of dissemination, and treatment response. This review synthesizes key recent developments in TB imaging, focusing on studies published since prior Seminars in Nuclear Medicine reviews. New non-human primate and human PET/CT data provide unprecedented insight into the spatial and temporal evolution of granulomas, demonstrating highly localized microanatomic seeding, bronchogenic spread pathways, and heterogeneous lesion biology that strongly influence treatment outcomes. Imaging studies in asymptomatic individuals reveal that metabolically active subclinical TB is common and strongly predictive of future progression, redefining the spectrum of latent infection. In treatment monitoring, FDG PET/CT consistently outperforms conventional microbiologic biomarkers, correlating with lesion-level sterilization and identifying patients at risk for relapse, particularly when persistent metabolic activity remains at the end of therapy. The introduction of emerging tracers, such as integrin-targeted probes, offers complementary characterization of granuloma angiogenesis, immune microenvironments, and host-pathogen dynamics beyond glucose metabolism. Future priorities include the development of TB-specific radiotracers, the integration of PET with advanced computational modeling and AI-based quantification, and the translation of imaging biomarkers into individualized treatment strategies and drug-development pipelines. Collectively, these advances position molecular imaging as a central tool in elucidating TB biology and accelerating progress toward improved diagnostic, therapeutic, and prevention strategies.

Oromandibular dyskinesia is an abnormal, repetitive, involuntary movement of the jaw, tongue, and lips. We report an interesting image of a 72-year-old woman, who underwent 18 F- FDG PET/CT for restaging of treated colon cancer. PET/CT scan shows diffuse uptake in orbicularis oris, muscles of the lips, muscles around the mandible and in the oral cavity, and anterior tongue muscles with no abnormality seen on corresponding CT images. A thorough search into patient history revealed the diagnosis of oromandibular dyskinesia.

Antibody-drug conjugates (ADCs) utilize monoclonal antibodies (mAbs) that target tumor-specific antigens to deliver potent cytotoxic chemotherapy payloads to the tumor, while sparing normal tissues. The chemotherapy agents employed in ADCs are very potent, causing a tumoricidal effect at low drug concentrations. Several ADCs have been approved for the treatment of different solid tumors over the last decade following the superior efficacy and safety they demonstrated above standard-of-care treatment modalities in several clinical trials. Despite their efficacy, some patients do not respond to treatment with ADCs, as objective response rate typically range from 30% to 50%, and as low as 20% in some instances. Some patients who initially respond to treatment develop acquired resistance during their treatment, necessitating strategies to improve response rates and overcome treatment resistance. Radiation from radionuclides, with their ability to evoke a synergistic antitumor effect when used in combination with cytotoxic chemotherapy and induce a tumoricidal effect in tumor cells remote from the tumor they are bound to (crossfire effect), has the potential to improve the outcomes of ADC treatment. An expanding body of evidence, reporting the successful radiolabeling of established and experimental ADCs, is emerging in the literature. These studies have demonstrated improved antitumor effect of radiolabeled ADC relative to cold ADC, paving the way for further exploration, including in clinical settings.

Purpose Recently developed digital positron emission tomography/computed tomography (PET/CT) scanners (digital PET [dPET]) have given new dimensions to molecular imaging. dPET scanner has very high sensitivity, spatial resolution, and image contrast that leads to increased uptake of signal in small-volume structures like pituitary gland (PG) making them visible on PET/CT scan even in absence of any pathology. Adequate knowledge of physiological fluoro-2 deoxy D glucose uptake in PG is required in interpretation of dPET for correct diagnosis and reducing unnecessary additional imaging. The aim of this study is to evaluate the frequency of physiological PG uptake on dPET. Material and Methods Eighty-eight subjects (mean age, 54.44 +/- 14.18 years; range, 26-84 years; 63 females and 25 males) with normal PG on magnetic resonance imaging brain and imaged within 6 months on dPET were included in this research study. Out of 88 patients, 20 control subjects (mean age, 58.15 +/- 11.08 years: 15 females and 5 males) underwent PET/CT on conventional PET. All images were acquired with similar and standard acquisition protocol and reconstruction done with Time of flight with Point spread function. PG uptake was compared visually and quantitatively. Results PG uptake was seen in 43 patients (48.8%). Out of 43 patients, 31 (72%) showed low uptake, 11 (26%) showed intermediate grade of uptake, and 1 patient (2%) showed intermediate-to-high uptake and was categorized as high-grade uptake. In the control group of 20 patients, 3 (15%) showed low uptake, while none of them showed intermediate or high uptake. Conclusions Physiological PG uptake is commonly seen on dPET. Low-to-intermediate grade of PG uptake on dPET in an asymptomatic patient is physiological and does not require further evaluation and should be reported with caution.

Theranostics with radioligands (radiotheranostics) has played a pivotal role in oncology. Radiotheranostics explores the molecular targets expressed on tumor cells to target them for imaging and therapy. In this way, radiotheranostics entails non-invasive demonstration of the in vivo expression of a molecular target of interest through imaging followed by the administration of therapeutic radioligand targeting the tumor-expressed molecular target. Therefore, radiotheranostics ensures that only patients with a high likelihood of response are treated with a particular radiotheranostic agent, ensuring the delivery of personalized care to cancer patients. Within the last decades, a couple of radiotheranostics agents, including Lutetium-177 DOTATATE (177Lu-DOTATATE) and Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA), were shown to prolong the survival of cancer patients compared to the current standard of care leading to the regulatory approval of these agents for routine use in oncology care. This recent string of successful approvals has broadened the interest in the development of different radiotheranostic agents and their investigation for clinical translation. In this work, we present an updated appraisal of the literature, reviewing the recent advances in the use of established radiotheranostic agents such as radioiodine for differentiated thyroid carcinoma and Iodine-131-labeled meta-iodobenzylguanidine therapy of tumors of the sympathoadrenal axis as well as the recently approved 177Lu-DOTATATE and 177Lu-PSMA for differentiated neuroendocrine tumors and advanced prostate cancer, respectively. We also discuss the radiotheranostic agents that have been comprehensively characterized in preclinical studies and have shown some clinical evidence supporting their safety and efficacy, especially those targeting fibroblast activation protein (FAP) and chemokine receptor 4 (CXCR4) and those still being investigated in preclinical studies such as those targeting poly (ADP-ribose) polymerase (PARP) and epidermal growth factor receptor 2.

Abstract Pulmonary hamartoma is the most common benign tumor of the lung and often discovered incidentally on imaging. We report the case of a 49-year-old woman recently diagnosed with left breast cancer with suspicious left axillary lymph nodes. 18F-FDG PET/CT showed well-circumscribed, lobulated, low-attenuation soft tissue mass in the right lower lobe lung with mild to no significant metabolic activity. CT-guided biopsy showed the lesion composed of fat, cartilage, and smooth muscle, admixed with fibroconnective tissue. The findings are consistent with pulmonary hamartoma. The presence of fat in a well-circumscribed solitary pulmonary nodule along with low metabolic activity helps in the characterization of the lesion, which can alter patient management.

SPECT/CT is a powerful tool for assessing unexpected concentrations of radioiodine resulting from benign uptake in organs with sodium-iodide symporter (NIS) expression. We report a case of accumulation of 131Iodine in the nasolacrimal sac/duct after radioiodine therapy for papillary thyroid cancer. A whole-body scan was taken 3 days after the administration of 5.5 GBq of 131Iodine. SPECT/CT images localized the focal tracer uptake in the nasolacrimal sac/duct likely due to nasolacrimal duct obstruction secondary to prior radioiodine or iodine therapies. Hybrid SPECT/CT allows precise anatomical localization and help differentiate benign mimics of disease, which can alter patient management.

68Ga-PMSA imaging has revolutionized both diagnosis and radioligand therapy selection in patients with metastatic prostate cancer. We report a case of a 59-year-old recently diagnosed prostate cancer with high PSA level pf >2000ng/ml referred for 68Ga-PSMA PET/CT. 68Ga-PSMA PET/CT showed diffuse intense tracer uptake throughout the axial and appendicular skeleton with significantly lower uptake of 68Ga-PSMA in normal organs in a configuration of "tumour sink effect". Findings are in keeping with diffuse skeletal infiltration and suspected marrow infiltration. Given the extensive nature of bone disease and pattern, 177Lu-PSMA-targetted radioligand therapy was thought to be more appropriate in a given situation with a favourable toxicity profile.

Breast cancer in women of African descent tends to be more aggressive with poorer prognosis. This is irrespective of the molecular subtype. [18F]FDG PET/CT metrics correlate with breast cancer aggressiveness based on molecular subtype. This study investigated the differences in [18F]FDG PET/CT metrics of locally advanced invasive ductal carcinoma (IDC) among different racial groups and molecular subtypes. Qualitative and semiquantitative readings of [18F]FDG PET/CT acquired in women with locally advanced IDC were performed. Biodata including self-identified racial grouping and histopathological data of the primary breast cancer were retrieved. Statistical analysis for differences in SUVmax, MTV and TLG of the primary tumour and the presence of regional and distant metastases was conducted based on molecular subtype and race. The primary tumour SUVmax, MTV, TLG and the prevalence of distant metastases were significantly higher in Black patients compared with other races (p < 0.05). The primary tumour SUVmax and presence of distant metastases in the luminal subtype and the primary tumour SUVmax and TLG in the basal subtype were significantly higher in Black patients compared with other races (p < 0.05). The significantly higher PET parameters in Black patients with IDC in general and in those with luminal and basal carcinoma subtypes suggest a more aggressive disease phenotype in this race.

ABSTRACT:Anomalous systemic arterial supply to normal lung is an anatomical variant in which a portion of the lung is supplied by a systemic vessel without a distinct pulmonary sequestration. We report a case of mild to moderate accumulation of 18 F-FDG in the medial basal segment of left lung; corresponding CT images localize this uptake in the tortuous artery arising from the descending aorta with similar uptake to that of descending aorta. Findings are suggestive of anomalous systemic arterial supply to normal segments of the lung. Hybrid PET/CT allows precise anatomical localization and helps in differentiate benign mimics of disease, which can alter patient management.

Meningiomas overexpress somatostatin receptors (SSTR). PET imaging with SSTR ligands such as 68Ga-DOTA-peptide has recently shown high diagnostic accuracy in identification of meningiomas due to lack of normal bone and brain activity. PET-derived parameters, especially gross tumour volume (GTV) delineation improves inter-observer variability and appears to be particularly promising for RT planning. The potential strength of 68Ga-DOTA in the ongoing assessment of treatment response and disease progression in meningioma, particularly in the post-surgical and post-radiation settings is encouraging. More prospective randomized studies with large cohorts of patients are required to define the effective role of this modality.

ABSTRACT:An 80-year-old man underwent [ 68 Ga]Ga-PSMA-11 PET/CT for staging of high-risk prostate cancer. Homogeneously increased liver uptake, more than 3-fold the splenic uptake, was seen. There was no hepatic lesion evident on CT. A higher liver to splenic uptake is more typical of some 18 F-labeled PSMA PET/CT but unusual in 68 Ga-labeled PSMA PET/CT scan. Further evaluation revealed a history of impaired renal function, bilateral renal atrophy, relatively decreased renal uptake of [ 68 Ga]Ga-PSMA-11, and prominent bowel activity. We concluded that impaired renal function and subsequent poor excretion resulted in increased hepatic excretion, hence the unusual increased homogeneous hepatic uptake.

Despite the introduction of many novel diagnostic techniques and newer treatment agents, tuberculosis (TB) remains a major cause of death from an infectious disease worldwide. With about a quarter of humanity harboring Mycobacterium tuberculosis, the causative agent of TB, the current efforts geared towards reducing the scourge due to TB must be sustained. At the same time, newer alternative modalities for diagnosis and treatment response assessment are considered. Molecular imaging entails the use of radioactive probes that exploit molecular targets expressed by microbes or human cells for imaging using hybrid scanners that provide both anatomic and functional features of the disease being imaged. Fluorine-18 fluorodeoxyglucose (FDG) is the most investigated radioactive probe for TB imaging in research and clinical practice. When imaged with positron emission tomography interphase with computed tomography (PET/CT), FDG PET/CT performs better than sputum conversion for predicting treatment outcome. At the end of treatment, FDG PET/CT has demonstrated the unique ability to identify a subset of patients declared cured based on the current standard of care but who still harbor live bacilli capable of causing disease relapse after therapy discontinuation. Our understanding of the pathogenesis and evolution of TB has improved significantly in the last decade, owing to the introduction of FDG PET/CT in TB research. FDG is a non-specific probe as it targets the host inflammatory response to Mycobacterium tuberculosis, which is not specifically different in TB compared with other infectious conditions. Ongoing efforts are geared towards evaluating the utility of newer probes targeting different components of the TB granuloma, the hallmark of TB lesions, including hypoxia, neovascularization, and fibrosis, in TB management. The most exciting category of non-FDG PET probes developed for molecular imaging of TB appears to be radiolabeled anti-tuberculous drugs for use in studying the pharmacokinetic characteristics of the drugs. This allows for the non-invasive study of drug kinetics in different body compartments concurrently, providing an insight into the spatial heterogeneity of drug exposure in different TB lesions. The ability to repeat molecular imaging using radiolabeled anti-tuberculous agents also offers an opportunity to study the temporal changes in drug kinetics within the different lesions during treatment.

PurposeThere are conflicting results from studies on whether ventilation scintigraphy can be safely omitted or replaced by chest radiography. These studies were based on planar ventilation/perfusion (V/Q) scintigraphy. We evaluated the value of the ventilation single-photon emission computed tomography (SPECT) on the final conclusion drawn from a V/Q SPECT and the possible role of the chest radiography as a surrogate for the ventilation SPECT.Patients and methodsRaw data of V/Q SPECT images and chest radiography acquired within 48h over an 18-month period were retrieved, reprocessed and reviewed in batches. The ventilation SPECT, perfusion SPECT and chest radiography were reviewed separately and in combination. Data on the presence and nature of defects and chest radiography abnormalities were recorded. The V/Q SPECT images were interpreted using the criteria in the EANM guideline and the perfusion SPECT and chest radiography images were interpreted using the PISAPED criteria. Agreement between the diagnosis on the V/Q SPECT review and the perfusion SPECT and chest radiography review was analysed.ResultsOverall, 21.1% of the patients were classified as PE present' on the V/Q SPECT review, whereas 48.9% were classified as PE present' on the perfusion SPECT and chest radiography review. Only 5.4% of defects observed on ventilation SPECT had matched chest radiography lung field opacity.ConclusionOur study showed that the omission of a ventilation SPECT led to a high rate of false-positive diagnoses and that the ventilation scan cannot be replaced by a chest radiography.

Malignant tumors account for most sources of ectopic ACTH Cushing syndrome (EA-CS). Early localization of the source and complete removal can be curative and also prevent metastasis. Diagnostic CT is known to perform better than PET/CT (low dose) in characterizing lung pathologies. However, bronchial carcinoids, a common source of EA-CS, may be difficult to detect on chest CT scan especially when it is small and located close to the hilar region. We present a case of EA-CS due to bronchial carcinoid, which was easily seen on Ga DOTANOC PET/CT after a diagnostic chest CT was reported as normal.