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.

A pleuroperitoneal leak (PPL) is a relatively rare complication of peritoneal dialysis (PD) and early diagnosis is essential. Patients suspected of a PPL usually present with dyspnea (marked during inflow of PD fluid) and tend to have transudative high glucose pleural effusions. The PPL scintigraphy (PPLS) is one of the methods for objectively proving a PPL. The effectiveness of PPLS as a noninvasive method of evaluating a suspected PPL and its effectiveness in the exclusion of a leak in patients with similarly presenting comorbidities was assessed. Patients suspected to have a PPL were considered for PPLS based on clinical presentation and pleural fluid analysis. Radiopharmaceutical was administered into the peritoneum via the dialysis port with the patient lying supine and immediate dynamic followed by delayed statics were acquired. Of the 27 scans reviewed, 70% were found to be positive with majority detected within 12 minutes of radiopharmaceutical administration with a high predominance occurring in the right chest (P < .001). In PPLS-positive patients, when both chest X-rays and planar agreed on showing the right-sided chest predominance, the highest measurements of the pleural glucose:serum glucose ratio were recorded. A statistically significant correlation between the outcome of the scan and final decision on patient management was noted (P < .01). The PPLS is an effective diagnostic tool for assessing PPLS. However, multicenter studies investigating its added value over other conventional methods are needed to establish it as a highly relevant diagnostic tool.

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: 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.