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.

1kwamnandi@gmail.com Introduction: Lutetium -177 (¹⁷⁷Lu) is a radionuclide with unique theranostic properties that make it ideal for radionuclide therapy. The use of ¹⁷⁷Lu has shown promising results in the treatment of different types of cancers, including neuroendocrine tumors and prostate cancer. Prostate cancer is the commonest malignancy in South African men and with a significant mortality and morbidity. Metastatic castration-resistant prostate cancer (mCRPC) is often treated with chemotherapy and immunotherapy; however, the survival benefits from these agents are modest with survival of less than 20 months. Neuroendocrine tumors (NET) are heterogeneous group of slow-growing tumors with membrane-bound secretory granules and an ability to produce specific peptides and hormones. Histologically confirmed well-differentiated NET- or moderately-differentiated NETs, G1, or G2 and not amenable to curative surgery may be treated with ¹⁷⁷Lu therapy. In order for patients to qualify for Lutetium-177 radionuclide therapy a renogram to assess kidney function and rule out obstruction is required. Other tests including a ⁶⁸Ga PSMA is also done. This study aimed to compare the effectiveness of Ga – 68 PSMA and Dotatate derived split renal function with diuretic renogram based split function in assessing the renal function. Methods: A retrospective analysis (visual and quantitative) was conducted on 21 patients with histologically confirmed prostate ca who are Metastatic castration-resistant prostate cancer (mCRPC) and 10 patients with histologically confirmed well-differentiated NET- or moderately-differentiated NETs, G1, or G2 and not amenable to curative surgery. Baseline renal function (urea and creatine), renogram parameters (split renal function), ⁶⁸Ga PSMA and Dotatate kidney findings were assessed. Renogram, ⁶⁸Ga PSMA, and ⁶⁸Ga Dotatate were done within a period of ±1 week of each other. Diuretic renogram split function was calculated with symbia.net software. To calculate relative ⁶⁸Ga PSMA and Dotatate distribution in both kidneys, volumes of interest were drawn and generated using syngo.via software. The volume and the mean standard uptake value (SUV_mean) were then used for calculating the split renal function (SRF). The following formula was used: SRF = (volume right × SUV_mean right)/(volume right × SUV_mean right + volume left × SUV_mean left) Results: Of the 31 patients with a mean age of 61 years, two were noted to have a difference in split function of more than 10% between the diuretic renogram and ⁶⁸Ga PSMA and Dotatate-derived split renal function. The balance of the patients demonstrated congruence between the diuretic renogram and ⁶⁸Ga PSMA and Dotatate-derived split renal function. Concordance was also noted between renal abnormalities on diuretic renogram and ⁶⁸Ga PSMA and Dotatate scans. These abnormalities included hydronephrosis, small shrunken kidneys which were poorly functioning or nonfunctional. Furthermore, the ⁶⁸Ga PSMA/Dotatate scans demonstrated simple kidney cysts in the various poles of the kidneys. Conclusions: The results showed that ⁶⁸Ga PSMA and Dotatate-derived split function had a high correlation with diuretic renogram based split function in assessing renal function. Moreover, these tests also provided additional information regarding the functional status of the kidneys. Apart from assessing function of the kidneys, anatomical defects can also be visually assessed. Therefore, it is suggested that ⁶⁸Ga PSMA and Dotatate-derived split renal function can be used as an alternative to diuretic renogram based split function. However, further studies are needed to confirm these findings and to determine if diuretic renogram would still be required in specific clinical scenarios. Article published online: 25 May 2023 © 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India