Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer worldwide, with an estimated 2.3 million new cases (11.7%), followed by lung cancer (11.4%) The current literature and the National Comprehensive Cancer Network (NCCN) guidelines state that ¹⁸F-FDG PET/CT is not routine for early diagnosis of breast cancer, and rather PET/CT scanning should be performed for patients with stage III disease or when conventional staging studies yield non-diagnostic or suspicious results because this modality has been shown to upstage patients compared to conventional imaging and thus has an impact on disease management and prognosis. Furthermore, with the growing interest in precision therapy in breast cancer, numerous novel radiopharmaceuticals have been developed that target tumor biology and have the potential to non-invasively guide the most appropriate targeted therapy. This review discusses the role of ¹⁸F-FDG PET and other PET tracers beyond FDG in breast cancer imaging.

Chemokine receptor CXCR4 is overexpressed in neoplasms and its expression is related to tumour invasion, metastasis and aggressiveness. ⁶⁸Ga-Pentixafor is used to non-invasively image the expression of CXCR4 in tumours and has been widely used in haematological malignancies. Recent evidence shows that therapies targeting CXCR4 can increase the chemosensitivity of the tumour as well as inhibit tumour metastasis and aggressiveness. ⁶⁸Ga-Pentixafor has shown promise as an elegant radiotracer to aid in the selection of patients whose tumours demonstrate CXCR4 overexpression and who therefore may benefit from novel therapies targeting CXCR4. In addition, its therapeutic partners ¹⁷⁷Lu- and ⁹⁰Y-Pentixather have been investigated in the treatment of patients with advanced haematological malignancies, and initial studies have shown a good treatment response in metabolically active lesions. ⁶⁸Ga-Pentixafor in solid tumours complements ¹⁸F-FDG by providing prognostic information and selecting patients who may benefit from therapies targeting CXCR4. This review summarises the available literature on the potential applications of ⁶⁸Ga-Pentixafor in solid tumours.

Background: Head and neck squamous cell carcinoma (HNSCC) is common, and its incidence is increasing, particularly in HIV-infected individuals who present with more aggressive disease. Despite aggressive treatment, the prognosis remains poor because of resistance to chemoradiation therapy. So far, studies report very low [⁶⁸Ga]Ga-Pentixafor avidity in HNSCC. This study investigated the diagnostic performance of CXCR4-directed imaging of carcinoma of the oral cavity, oropharynx, and nasopharynx with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine ligand [⁶⁸Ga]Ga-Pentixafor and explored its ability to quantify CXCR4 expression in vivo. Materials and Methods: In this prospective cross-sectional study, twenty-three (23) patients aged 52.9 ± 10.4 (19.6), 17 males and 6 females with primarily diagnosed (n = 17) or pre-treated (n = 6) SCC of the oral cavity (OCSCC, n = 11), oropharynx (OPSCC, n = 9), nasopharynx (NPSCC, n = 2) and unknown primary (n = 1) underwent imaging with [⁶⁸Ga]Ga-Pentixafor-PET/CT. In 16/23 patients 2-[18F]fluoro-2-deoxy-D-glucose ([¹⁸F]F-FDG) served as a standard reference. All lesions were visually rated using a 5-point Likert scale. For both tracers, maximum standardized uptake values (SUVmax) and the total lesion uptake (TLU) were recorded and compared using the Wilcox-signed rank test. In addition, the tumor-to-background ratios were derived using the liver (TLR), spleen (TSR), and posterior cervical muscles (TMR) as background. The relationships between the SUVs of the two tracers were assessed using the Spearman correlation. CXCR4 immunohistochemistry (IHC) staining was correlated with ⁶⁸Ga-Pentixafor-PET/CT in 21/23 patients. Results: Ninety-one percent (21/23) of tumors were visually detected on [⁶⁸Ga]Ga-Pentixafor; however, [⁶⁸Ga]Ga-Pentixafor was less intense compared with [¹⁸F]F-FDG-PET. Quantitative analysis showed higher [¹⁸F]F-FDG SUVmax in comparison with [⁶⁸Ga]Ga-Pentixafor (16 ± 6.7 vs. 5.8 ± 2.6 g/mL, p = 0.011) and SUVmean (9.3 ± 4.1 vs. 3± 1.6 g/mL, p < 0.001) and TBR 4.9 ± 2.3 vs. 2.36 ± 1.4 p = 0.014. Nasopharyngeal cancer demonstrated more intense tracer accumulation than oropharyngeal and oral cavity malignancies. CXCR4 IHC staining was positive in 15/21 patients, and there was a statistically significant correlation between IHC staining and [⁶⁸Ga]Ga-Pentixafor SUVmean r = 0.5 p = 0.027, and performance status r = 0.83 p = 0.0104. Conclusions: In conclusion, although [⁶⁸Ga]Ga-Pentixafor cannot replace [¹⁸F]F-FDG as a diagnostic tool because of its lower avidity, the correlation between CXCR4 targeted ⁶⁸Ga-Pentixafor PET imaging and CXCR4 IHC staining indicates the potential of ⁶⁸Ga-Pentixafor as an effective tool for selecting patients who may benefit from therapies targeting CXCR4. In addition, [⁶⁸Ga]Ga-Pentixafor has no physiological brown fat uptake, which often obscures cervical lesions on [¹⁸F]F-FDG PET/CT imaging.

Background. CXCR4 is a chemokine receptor that is frequently overexpressed in invasive breast cancer and plays a major role in tumor proliferation, aggressiveness and metastasis. The aim of this prospective study was to establish the value of CXCR4-directed PET imaging in patients with breast cancer using the novel CXCR4-targeted PET probe ⁶⁸Ga-Pentixafor by comparing it with ¹⁸F-FDG PET/CT (n = 40). Materials and methods. In this prospective cross-sectional study, fifty-one patients with breast cancer aged 36–81 (median (Q1-Q3) 51 (42.5–63)), n = 47 (92%) with initially diagnosed and n = 4 (8%) patients with recurrent breast cancer, underwent CXCR4-targeted PET imaging using ⁶⁸Ga-Pentixafor. Maximum standardized uptake values (SUVmax), total lesion glycolysis (TLG) or total lesion uptake (TLU), metabolic tumor volume (MTV) and tumor-to-background ratios (TBR) of tumor lesions were measured and correlated with pathological prognostic factors, molecular subtypes and CXCR4 immunohistochemistry (IHC) staining. ¹⁸F-FDG PET/CT images were available in 40 of 51 cases (82%) and were compared semi-quantitatively. The patients were followed up for a median of 11 months (range 4–80 months) to determine whether CXCR4 expression correlated with survival. Results. ⁶⁸Ga-Pentixafor-PET/CT was visually positive in 49/51 (96%) of the cases; in addition, [¹⁸F]FDG demonstrated a higher SUVmax compared to ⁶⁸Ga-Pentixafor. The mean SUVmax was 7.26 ± 2.84 and 18.8 ± 9.1 for ⁶⁸Ga-Pentixafor and [¹⁸F]FDG, respectively. Thirty-seven percent (18/51) of patients had triple-negative breast cancer and 25/51 (49%) had estrogen receptor (ER+) disease. There was a statistically significant correlation between tumor grade, proliferative index (Ki-67) and SUVmax obtained from ⁶⁸Ga-Pentixafor PET p = 0.002. There was no correlation between the SUVmax obtained from ⁶⁸Ga-Pentixafor and PET molecular subtypes, estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2) status; however, triple-negative breast cancers had more avid ⁶⁸Ga-Pentixafor accumulation compared to luminals A and B. The median (Q1–Q3) ⁶⁸Ga-Pentixafor TLU was significantly higher in HIV-positive (376 (219–881)) compared to HIV-negative (174 (105–557)) breast cancer patients. Conclusions. In conclusion, ⁶⁸Ga-Pentixafor had a sensitivity of 96% and a specificity of 100% for detecting primary breast cancer; in addition, ⁶⁸Ga-Pentixafor exhibited significantly higher uptake in patients with higher tumor grade, high proliferative index and triple-negative breast cancer (TNBC), as well as HIV-infected breast cancer patients, highlighting the potential clinical utility and prognostic role of CXCR4-targeted PET imaging in aggressive breast cancer. Notably, ⁶⁸Ga-Pentixafor complements ¹⁸F-FDG by detecting more metastasis in the brain and the skull where FDG has limitations, while ¹⁸F-FDG remains superior for detecting skeletal metastasis. Future research should further explore the potential of CXCR4-targeted PET imaging in selecting patients with triple-negative breast cancer and high-grade breast cancer who may benefit from CXCR4-targeted therapies, particularly in the context of HIV co-infection.

Background: Physiological PSMA expression in the cells of the proximal renal tubules and consecutive radiopharmaceutical binding and retention could potentially lead to radioligand-therapy-induced nephrotoxicity. Thus, patients with metastatic castration-resistant prostate cancer undergo ^99mTc-Mercaptoacetyltriglycine (MAG3) renal scintigraphy to assess kidney function and to exclude renal obstruction as part of their workup for PSMA-targeted radioligand therapy (RLT). ^99mTc-MAG-3 renal scintigraphy often requires an additional visit to the nuclear medicine department and patients spend 30–90 min in the department, which is inconvenient and takes up camera time. In addition, the patients are subjected to a baseline ⁶⁸Ga-PSMA PET/CT to assess for PSMA-positive disease prior to targeted radioligand therapy. The aim of this retrospective cross-sectional study was to compare ^99mTc-MAG-3-based split renal function (SRF) with ⁶⁸Ga-PSMA-derived SRF. Methods: This retrospective cross-sectional study included 28 patients with histologically proven metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA617. A comparison between the split renal function using ⁶⁸Ga-PSMA PET/CT and the ^99mTc-MAG-3-derived split renal function was carried out in 56 kidneys (n = 56). The SRF on ⁶⁸Ga-PSMA was calculated using the volume and the average standard uptake value (SUVmean) within each VOI calculated as previously described by Roser et al.: SRF = (VOLUME_right) ∗ SUVmean_right/(VOLUME_right ∗ SUVmean_right + VOLUME_left ∗ SUVmean_left). Paired tests and correlation coefficients were used to compare ⁶⁸Ga-PSMA and ^99mTc-MAG-3. A visual comparison of kidney morphology on both studies was also performed. Results: The median SRF of the right kidney was 49.9% (range: 3–91%) using ⁶⁸Ga-PSMA PET/CT and 50.5% (range: 0–94%) with ^99mTc-MAG3 scintigraphy. Notably, there was a strong correlation between SRF measurements obtained from PSMA and ^99mTcMAG3, with a Pearson correlation coefficient of 0.957 (p < 0.001). Both ^99mTc-MAG3 and ⁶⁸Ga-PSMA PET/CT studies identified morphological renal abnormalities; there were nine hydronephrotic kidneys, four shrunken kidneys and one obstructed kidney, and there was a strong positive correlation between ⁶⁸Ga-PSMA kidney morphology and ^99mTcMAG3 renal scintigraphy kidney morphology, with a correlation coefficient of 0.93. Conclusions: PSMA-derived split function demonstrated a high correlation with renal function assessed on diuretic ^99mTc-MAG3 renograms. PET-derived split renal function may, therefore, be considered an alternative to diuretic renogram-based split function. Furthermore, both ^99mTc-MAG3 and ⁶⁸Ga-PSMA PET/CT studies identified morphological renal abnormalities such as hydronephrosis, shrunken and obstructed kidneys. This correlation underscores the potential utility of ⁶⁸Ga-PSMA imaging as a valuable tool for assessing kidney morphology as an alternative to renogram split function in clinical practice.

Surgery and imatinib are the mainstays of the management of gastrointestinal stromal tumours (GIST). This study aimed to analyse the outcomes in the management of GIST utilising surgery and imatinib. Progression-free survival (PFS) and overall survival (OS) were analysed in relation to imatinib therapy, location of tumour, resection margins, type and extent of surgery. Imatinib was administered in the neoadjuvant (maximum 12 months) and adjuvant setting (minimum 36 months) and until disease progression or drug intolerance. Disease response was assessed with the Choi criteria. Survival analysis included calculation of PFS, OS and Kaplan-Meier curves. Sixty-two patients were reviewed and 56 had surgical resection. The median age (range) was 58.5 (8-95) years. The median PFS and OS (IQR) was 24.0 (0-52.0) and 41.0 (15.0-74.0) months, respectively. Thirty-nine (70%) patients were treated with imatinib, with 21 of these in a neoadjuvant setting. In the patients undergoing surgery, surgical margins were R0, R1 and R2 in 41 (75%), eight (15%) and six (11%) respectively. There was an insignificant difference in the overall survival in these three groups. For those having liver metastasectomy and multivisceral resection, the PFS and OS were 32.5 (17.5-60.3) and 28.5 (5.75-49.8) (p = 0.008), and 96.0 (58.5-116) and 80 (50.5-92.3) months (p = 0.033), respectively. Whilst the numbers were small, certain trends were observed. Surgery in combination with imatinib offers survival benefit in patients undergoing R0, R1, R2, liver metastases and multivisceral resections.