Hypoxia leads to changes in tumor microenvironment (upregulated CAFs) with resultant aggressiveness. A key factor in the physiological response to hypoxia is hypoxia-inducible factor-1alpha (HIF-1$\alpha$). [⁶⁸Ga]Ga-FAPI PET imaging has been demonstrated in various cancer types. We hypothesized that [⁶⁸Ga]Ga-FAPI PET may be used as an indirect tracer for mapping hypoxia by correlating the image findings to pathological analysis of HIF-1$\alpha$ expression. The [⁶⁸Ga]Ga-FAPI PET/CT scans of women with cancer of the cervix were reviewed and the maximum and mean standardized uptake value (SUVmax and SUVmean) and FAPI tumor volume (FAPI-TV) were documented. Correlation analysis was performed between PET-derived parameters and immunohistochemical staining as well as between PET-derived parameters and the presence of metastasis. Ten women were included. All patients demonstrated tracer uptake in the primary site or region of the primary. All patients had lymph node metastases while only six patients had distant visceral or skeletal metastases. The mean SUVmax, SUVmean, and FAPI-TV was 18.89, 6.88, and 195.66 cm³, respectively. The average FAPI-TV for patients with additional sites of metastases was higher than those without. Immunohistochemistry revealed varying intensities of HIF-1$\alpha$ expression in all tested samples. There was a positive correlation between the presence of skeletal metastases and staining for HIF-1$\alpha \left(r=0.80;p=0.017\right)$. The presence of skeletal metastasis was correlated to the HIF-1⍺ staining (percentage distribution). Furthermore, the FAPI-TV was a better predictor of metastatic disease than the SUVmax.

People living with human immunodeficiency virus (PLHIV) have excess risk of atherosclerotic cardiovascular disease (ASCVD). Arterial inflammation is the hallmark of atherogenesis and its complications. In this study we aimed to perform a head-to-head comparison of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) and Gallium-68 pentixafor positron emission tomography/computed tomography [⁶⁸Ga]Ga-pentixafor PET/CT for quantification of arterial inflammation in PLHIV. We prospectively recruited human immunodeficiency virus (HIV)-infected patients to undergo [¹⁸F]FDG PET/CT and [⁶⁸Ga]Ga-pentixafor PET/CT within two weeks of each other. We quantified the levels of arterial tracer uptake on both scans using maximum standardized uptake value (SUVmax) and target–background ratio. We used Bland and Altman plots to measure the level of agreement between tracer quantification parameters obtained on both scans. A total of 12 patients were included with a mean age of 44.67 ± 7.62 years. The mean duration of HIV infection and mean CD+ T-cell count of the study population were 71.08 ± 37 months and 522.17 ± 260.33 cells/µL, respectively. We found a high level of agreement in the quantification variables obtained using [¹⁸F]FDG PET and [⁶⁸Ga]Ga-pentixafor PET. There is a good level of agreement in the arterial tracer quantification variables obtained using [¹⁸F]FDG PET/CT and [⁶⁸Ga]Ga-pentixafor PET/CT in PLHIV. This suggests that [⁶⁸Ga]Ga-pentixafor may be applied in the place of [¹⁸F]FDG PET/CT for the quantification of arterial inflammation.

Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper single-strand deoxyribonucleic acid (DNA) repair by trapping poly(ADP-ribose)polymerase (PARP) at sites of DNA damage, forming a non-functional “PARP enzyme–inhibitor complex” leading to cell cytotoxicity. The effect is more pronounced in the presence of PARP upregulation and homologous recombination (HR) deficiencies such as breast cancer-associated gene (BRCA1/2). Hence, identifying HR-deficiencies by genomic analysis—for instance, BRCA1/2 used in triple-negative breast cancer—should be a part of the selection process for PARP inhibitor therapy. Published data suggest BRCA1/2 germline mutations do not consistently predict favorable responses to PARP inhibitors, suggesting that other factors beyond tumor mutation status may be at play. A variety of factors, including tumor heterogeneity in PARP expression and intrinsic and/or acquired resistance to PARP inhibitors, may be contributing factors. This justifies the use of an additional tool for appropriate patient selection, which is noninvasive, and capable of assessing whole-body in vivo PARP expression and evaluating PARP inhibitor pharmacokinetics as complementary to the currently available BRCA1/2 analysis. In this review, we discuss [¹⁸F]Fluorine PARP inhibitor radiotracers and their potential in the imaging of PARP expression and PARP inhibitor pharmacokinetics. To provide context we also briefly discuss possible causes of PARP inhibitor resistance or ineffectiveness. The discussion focuses on TNBC, which is a tumor type where PARP inhibitors are used as part of the standard-of-care treatment strategy.

Breast cancer is the most frequently diagnosed cancer and leading cause of cancer-related deaths worldwide. Timely decision-making that enables implementation of the most appropriate therapy or therapies is essential for achieving the best clinical outcomes in breast cancer. While clinicopathologic characteristics and immunohistochemistry have traditionally been used in decision-making, these clinical and laboratory parameters may be difficult to ascertain or be equivocal due to tumor heterogeneity. Tumor heterogeneity is described as a phenomenon characterized by spatial or temporal phenotypic variations in tumor characteristics. Spatial variations occur within tumor lesions or between lesions at a single time point while temporal variations are seen as tumor lesions evolve with time. Due to limitations associated with immunohistochemistry (which requires invasive biopsies), whole-body molecular imaging tools such as standard-of-care [¹⁸F]FDG and [¹⁸F]FES PET/CT are indispensable in addressing this conundrum. Despite their proven utility, these standard-of-care imaging methods are often unable to image a myriad of other molecular pathways associated with breast cancer. This has stimulated interest in the development of novel radiopharmaceuticals targeting other molecular pathways and processes. In this review, we discuss validated and potential roles of these standard-of-care and novel molecular approaches. These approaches’ relationships with patient clinicopathologic and immunohistochemical characteristics as well as their influence on patient management will be discussed in greater detail. This paper will also introduce and discuss the potential utility of novel PARP inhibitor-based radiopharmaceuticals as non-invasive biomarkers of PARP expression/upregulation.

Targeted alpha therapy (TAT) with ²¹²Pb is rapidly emerging as a potent modality for cancer treatment due to the high linear energy transfer and short path length of α-particles, which enable precise tumor cell killing while sparing surrounding healthy tissue. Its elementally identical theranostic partner, ²⁰³Pb, functions as a γ-emitting surrogate for quantitative SPECT imaging, providing essential information for patient-specific dosimetry and treatment planning. Advances in SPECT imaging, ranging from NaI(Tl)-based dual-head systems to CZT multi-detector gamma cameras, have enhanced spatial resolution, quantitative accuracy, and lesion detectability, enabling rapid patient scanning and improved activity quantification for dosimetry. Clinical dosimetry workflows that integrate serial ²⁰³Pb SPECT/CT acquisitions, pharmacokinetic modeling, and image-based activity quantification facilitate reliable generation of time-activity curves and absorbed dose estimates. Organ-level and voxel-based dosimetry, combined with advanced reconstruction and microdosimetric modeling, further refine dose calculations, supporting individualized therapy planning. Collectively, these developments highlight the translational potential of the ²⁰³Pb/²¹²Pb theranostic pair. The aim of this review is to provide a comprehensive assessment of ²¹²Pb-TAT, encompassing clinical applications, surrogate imaging with ²⁰³Pb, gamma camera performance, dosimetry workflows, and predictive activity quantification, illustrating how these advances collectively enable quantitative, patient-specific, and theranostic-integrated radionuclide therapy.