Despite the progress in the quality of multiphasic CT and MRI scans, it is still difficult to fully characterize a solid kidney lesion. Approximately 10% of all solid renal tumours turn out to be oncocytomas. In actual clinical practice, this is verified only following unnecessary surgery or a renal biopsy/ablation. The objective of our pilot study examines whether 99mTc-sestamibi SPECT/CT can play a crucial role in the characterization of solid renal neoplasms and the differentiation of oncocytomas from renal cell carcinomas. The study included 27 patients identified with 31 solid renal lesions. All patients were discussed in a multidisciplinary conference, and a decision for surgery or biopsy was taken. Prior to invasive procedures, patients underwent a SPECT/CT with 99mTc-sestamibi. Visual evaluation was performed, and any focal 99mTc-sestamibi uptake detected on SPECT in the localisation of tumour was considered as positive. Eleven out of 12 oncocytomas (91.6%) displayed positive uptake of 99mTc-sestamibi. Three hybrid tumours (mixed-type oncocytoma and chromophobe renal cancer) were positive on SPECT/CT. One papillary renal cell carcinoma had a slight uptake of 99mTc-sestamibi. The remaining 11 renal cell carcinomas were sestamibi negative. Differentiation of benign renal oncocytomas from renal cell carcinomas seems very promising on 99mTc-sestamibi SPECT/CT examination. Additional supplement to visual evaluation, i.e. quantitative tools, should be sought for an accurate estimate of biological behaviour and hence a secure diagnosis.

Background: The α_vβ₃ integrin is one of the angiogenesis-related membrane proteins highly expressed on the neovasculature of breast cancer and lung carcinomas. Labeling of the α_vβ₃ integrin with ^99mTc-NC100692 provides a potential tool for imaging angiogenesis and hence the presence of malignant lesions. Purpose: To determine the feasibility of detecting metastatic lesions in liver, lung, bone, and brain with scintigraphy using the α_vβ₃-avid imaging agent ^99mTc-NC100692 in patients with breast or lung cancer, and to assess its safety profile. Material and Methods: Twenty-five patients—15 with lung cancer and 10 with breast cancer—were recruited at 10 centers. Metastases were newly diagnosed by computed tomography, magnetic resonance imaging, or bone scintigraphy, i.e., the reference standard. Patients underwent whole-body scans of approximately 10–15 min duration beginning at 45 min post-injection and a SPECT acquisition of approximately 30 min beginning at 75 min after injection of up to 1100 MBq ^99mTc-NC100692. In case of liver metastases, dynamic acquisitions of 15 min were performed starting immediately post-injection. Safety measurements were performed up to 2.5 hours after injection and included hematology, serum biochemistry, coagulation, urine analysis, vital signs, oximetry, 12-lead ECG assessments, and a physical examination. Results: In patients with breast cancer, ^99mTc-NC100692 scintigraphy detected 1 of 7 liver, 4 of 5 lung, 8 of 17 bone, and 1 of 1 brain metastases. The corresponding numbers for lung cancer patients were 0 of 2, 17 of 18, 2 of 2, and 7 of 9. There was overall stability through the follow-up period for all investigated safety parameters. Conclusion: Scintigraphy with ^99mTc-NC100692 is feasible for detection of lung and brain metastases from breast and lung cancer, while the detection of liver and bone lesions is poor. The use of ^99mTc-NC100692 is safe and well tolerated.

Purpose Patients with clinically node-positive breast cancer planned for neoadjuvant systemic therapy (NAST) may draw advantages from the nodal downstaging effect and reduce the extent of axillary surgery with sentinel lymph node biopsy (SLNB) performed after NAST. Since there are concerns about lower sentinel lymph node (SLN) detection and higher false-negative rates (FNR) in this setting, our aim was to define the accuracy of SLNB after NAST. Methods This Swedish national multicenter trial prospectively recruited 195 breast cancer patients from ten hospitals with T1–T4d biopsy-proven node-positive disease planned for NAST between October 1, 2010 and December 31, 2015. Clinically node-negative axillary status after NAST was not mandatory. SLNB was always attempted and followed by a completion axillary lymph node dissection (ALND). Results The SLN identification rate was 77.9% (152/195) but improved to 80.7% (138/171) with dual mapping. The median number of SLNs was two (range 1–5). A positive SLNB was found in 52% (79/152), almost 66% (52/79) of whom had additional positive non-sentinel lymph nodes. The overall pathologic nodal response rate was 33.3% (66/195). The overall FNR was 14.1% (13/92) but decreased to 4% (2/50) when only patients with two or more sentinel nodes were analyzed. Conclusions In biopsy-proven node-positive breast cancer, SLNB after NAST is feasible even though the identification rate is lower than in clinically node-negative patients. Since the overall FNR is unacceptably high, the omission of ALND should only be considered if two or more SLNs are identified.

Human epidermal growth factor receptor 2 (HER2) is a major prognostic and predictive marker overexpressed in 15–20% of breast cancers. The diagnostic reference standard for selecting patients for HER2-targeted therapy is based on the analysis of tumor biopsies. Previously patients were defined as HER2-positive or -negative; however, with the approval of novel treatment options, specifically the antibody–drug conjugate trastuzumab deruxtecan, many breast cancer patients with tumors expressing low levels of HER2 have become eligible for HER2-targeted therapy. Such patients will need to be reliably identified by suitable diagnostic methods. Biopsy-based diagnostics are invasive, and repeat biopsies are not always feasible. They cannot visualize the heterogeneity of HER2 expression, leading to a substantial number of misdiagnosed patients. An alternative and highly accurate diagnostic method is molecular imaging with radiotracers. In the case of HER2, various studies demonstrate the clinical utility and feasibility of such approaches. Radiotracers based on Affibody^® molecules, small, engineered affinity proteins with a size of ~6.5 kDa, are clinically validated molecules with favorable characteristics for imaging. In this article, we summarize the HER2-targeted therapeutic landscape, describe our experience with imaging diagnostics for HER2, and review the currently available clinical data on HER2-Affibody-based molecular imaging as a novel diagnostic tool in breast cancer and beyond.

Background: In the present study, we used multimodal imaging to investigate biodistribution in rats after intravenous administration of a new ^99mTc-labeled delivery system consisting of polymer-shelled microbubbles (MBs) functionalized with diethylenetriaminepentaacetic acid (DTPA), thiolated poly(methacrylic acid) (PMAA), chitosan, 1,4,7-triacyclononane-1,4,7-triacetic acid (NOTA), NOTA-super paramagnetic iron oxide nanoparticles (SPION), or DTPA-SPION. Methods: Examinations utilizing planar dynamic scintigraphy and hybrid imaging were performed using a commercially available single-photon emission computed tomography (SPECT)/computed tomography (CT) system. For SPION containing MBs, the biodistribution pattern of ^99mTc-labeled NOTA-SPION and DTPA-SPION MBs was investigated and co-registered using fusion SPECT/CT and magnetic resonance imaging (MRI). Moreover, to evaluate the biodistribution, organs were removed and radioactivity was measured and calculated as percentage of injected dose. Results: SPECT/CT and MRI showed that the distribution of ^99mTc-labeled ligand-functionalized MBs varied with the type of ligand as well as with the presence of SPION. The highest uptake was observed in the lungs 1 h post injection of ^99mTc-labeled DTPA and chitosan MBs, while a similar distribution to the lungs and the liver was seen after the administration of PMAA MBs. The highest counts of ^99mTc-labeled NOTA-SPION and DTPA-SPION MBs were observed in the lungs, liver, and kidneys 1 h post injection. The highest counts were observed in the liver, spleen, and kidneys as confirmed by MRI 24 h post injection. Furthermore, the results obtained from organ measurements were in good agreement with those obtained from SPECT/CT. Conclusions: In conclusion, microbubbles functionalized by different ligands can be labeled with radiotracers and utilized for SPECT/CT imaging, while the incorporation of SPION in MB shells enables imaging using MR. Our investigation revealed that biodistribution may be modified using different ligands. Furthermore, using a single contrast agent with fusion SPECT/CT/MR multimodal imaging enables visualization of functional and anatomical information in one image, thus improving the diagnostic benefit for patients.

By using solid targets in medical cyclotrons, it is possible to produce large amounts of ⁶⁸GaCl₃. Purification of Ga³⁺ from metal ion impurities is a critical step, as these metals compete with Ga³⁺ in the complexation with different chelators, which negatively affects the radiolabeling yields. In this work, we significantly lowered the level of iron (Fe) impurities by adding ascorbate in the purification, and the resulting ⁶⁸GaCl₃could be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. ⁶⁸GaCl₃ was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. The ⁶⁸Ga eluate was analyzed for radionuclidic purity (RNP) by gamma spectroscopy, metal content by ICP-MS, and by titrations with the chelators DOTA, NOTA, and HBED. The ⁶⁸GaCl₃eluate was utilized for GMP-radiolabeling of the DOTA-based tracers DOTATOC and FAPI-46 using an automated synthesis module. DOTA chelator titrations gave an apparent molar activity (AMA) of 491 ± 204 GBq/µmol. GMP-compliant syntheses yielded up to 7 GBq/batch [⁶⁸Ga]Ga-DOTATOC and [⁶⁸Ga]Ga-FAPI-46 (radiochemical yield, RCY ~ 60%, corresponding to ten times higher compared to generator-based productions). Full quality control (QC) of ⁶⁸Ga-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis.