<p dir="ltr">Pancreatic cancer remains one of the most lethal malignancies, largely due to late diagnosis, complex tumor biology, and limitations of conventional imaging in early detection, lesion characterization, and treatment response assessment. A defining biological feature of pancreatic ductal adenocarcinoma is its dense desmoplastic stroma, dominated by cancer-associated fibroblasts that express fibroblast activation protein. Targeting this stromal component offers a biologically distinct imaging signal compared with conventional morphologic or metabolic approaches and may improve biological lesion characterization in diagnostically challenging settings.</p><p dir="ltr">The overall aim of this thesis was to evaluate the clinical utility of [68Ga]Ga-FAPI- 46 positron emission tomography/computed tomography (PET/CT) for imaging- based assessment of pancreatic cancer in selected clinically relevant decision- making contexts. Four substudies, embedded within a prospective Phase II clinical trial, investigated tumor characterization and diagnostic performance, temporal uptake behavior and differentiation from inflammatory disease, optimization of acquisition protocols and image quality, as well as evaluation of treatment response following neoadjuvant therapy.</p><p dir="ltr">Paper I investigated the diagnostic accuracy of FAPI PET/CT in patients with suspected pancreatic or periampullary tumors scheduled for surgical exploration. FAPI PET/CT demonstrated high sensitivity and excellent lesion conspicuity for malignant disease, with particular value in cases where conventional imaging was equivocal. Quantitative uptake thresholds enabled reliable differentiation between malignant and benign pathology in this surgically verified cohort, supporting the role of stromal-targeted imaging as a complementary diagnostic tool in preoperative scenarios with high diagnostic uncertainty.</p><p dir="ltr">Paper II addressed methodological optimization by evaluating whether PET acquisition time could be reduced without compromising image quality or quantitative reliability. Visual grading and quantitative analyses showed that three-minute acquisitions preserved diagnostic image quality, standardized uptake values, and lesion-to-background ratios, supporting the feasibility of streamlined protocols suitable for routine clinical implementation and advanced imaging strategies.</p><p dir="ltr">Paper III explored temporal uptake patterns to improve differentiation between pancreatic cancer and chronic pancreatitis. While early single-time-point uptake demonstrated overlap between malignant and inflammatory lesions, relative changes in uptake over time provided superior discrimination. Relative SUVmax change achieved the highest diagnostic performance, with delayed imaging offering incremental value. A 60-minute relative change metric retained high discriminatory performance at a clinically practical and patient-convenient time point.</p><p dir="ltr">Paper IV evaluated the role of post-neoadjuvant FAPI PET/CT for treatment response assessment and perivascular evaluation in a clinically responder- selected cohort. No significant associations were observed between whole- tumor FAPI uptake and histopathological TRG, reflecting both cohort characteristics and the biological persistence of stromal activation after therapy. However, exploratory vessel-level analyses demonstrated a directional relationship between perivascular FAPI uptake and histopathologic vascular involvement, suggesting potential complementary value in evaluating equivocal vascular findings after neoadjuvant treatment.</p><p dir="ltr">In conclusion, [68Ga]Ga-FAPI-46 PET/CT provides high diagnostic sensitivity and conspicuity in untreated pancreatic cancer, particularly in cases where routine clinical imaging is inconclusive. Acquisition time optimization supports practical clinical implementation, and temporal imaging enhances lesion characterization where fibro-inflammatory overlap limits specificity. Conversely, isolated post- therapy FAPI PET snapshots may struggle to accurately reflect histopathologic regression, indicating the importance of baseline or longitudinal imaging strategies in response assessment. Together, the findings define clinically relevant contexts in which stromal-targeted PET adds value to current pancreatic cancer imaging pathways and establish a foundation for future prospective and longitudinal studies.</p><h3 dir="ltr">List of scientific papers</h3><p dir="ltr">I. <b>Rasinski P,</b> af Buren S, Holstensson M, Nilsson T, Loizou L, Tran TA, Sparrelid E, Löhr JM, Axelsson R. Tumor Characterization by [68Ga]FAPI-46 PET/CT Can Improve Treatment Selection for Pancreatic Cancer Patients: An Interim Analysis of a Prospective Clinical Trial. J Nucl Med 2023; 64: 1232-1237. <a href="https://doi.org/10.2967/jnumed.123.265481" rel="noreferrer" target="_blank">https://doi.org/10.2967/jnumed.123.265481</a></p><p dir="ltr">II. Nilsson T, <b>Rasinski P,</b> Smedby Ö, af Buren S, Sparrelid E, Löhr JM, Tran TA, Blomgren A, Tzortzakakis A, Axelsson R, Holstensson M. Acquisition Duration Optimization Using Visual Grading Regression in [68Ga]FAPI-46 PET Imaging of Oncologic Patients. J Nucl Med Technol 2024; 52: 221-228. <a href="https://doi.org/10.2967/jnmt.123.267156" rel="noreferrer" target="_blank">https://doi.org/10.2967/jnmt.123.267156</a></p><p dir="ltr">III. <b>Rasinski P,</b> Nilsson T, Peillon A, Holstensson M, Tzortzakakis A, Moro CF, Tran TA, Sparrelid E, Löhr JM, Axelsson R. Timing is Everything: Unmasking Pancreatic Cancer with Dual and Multiple-Timepoint [68Ga]Ga-FAPI-46 PET Imaging [Submitted] </p><p dir="ltr">IV. <b>Rasinski P,</b> Loizou L, Molina Centelles MF, Tzortzakakis A, Peillon A, Søreide K, Sparrelid E, Axelsson R, Ghorbani P. Post-Neoadjuvant FAPI PET/CT in Pancreatic Cancer: Response Assessment and Perivascular Evaluation [Manuscript]</p>
Read more