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1.
Artigo em Inglês | MEDLINE | ID: mdl-38977419

RESUMO

Introduction: The expression of alpha-five beta-three (αVß3) integrins is upregulated in various malignancies undergoing angiogenesis. The development of integrin antagonists as diagnostic probes makes the αVß3 integrin a suitable candidate for targeting tumor angiogenesis. The goal of this study was to optimize the radiolabeling and evaluate the potential of conjugated integrin antagonist carbamate (IAC), a peptidomimetic, as a theranostic radiopharmaceutical for targeting tumor angiogenesis. Methodology: Radiolabeling of DOTAGA [2,2',2" -{10-(2,6-dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl} triacetic-acid]-IAC with [68Ga]Ga, [177Lu]Lu, and [225Ac]Ac was optimized. The binding affinity (Kd) of DOTAGA-IAC for the αVß3 receptor and cancer cell lines was quantified. The biodistribution studies were conducted in healthy Wistar rats. Dosimetry analysis was performed on [177Lu]Lu-DOTAGA-IAC distribution data. A pilot study of [68Ga]Ga-DOTAGA-IAC and [18F]FDG Positron Emission Tomography (PET/CT) imaging was performed in five patients with histopathologically confirmed breast cancer. PET/CT findings were compared between [68Ga]Ga-DOTAGA-IAC and [18F]FDG in these patients. Results: Radiopharmaceuticals were prepared with high radiochemical purity (>99.9%). Kd and Bmax measurements were 15.02 nM and 417 fmol for αVß3 receptor protein: 115.7 nM and 295.3 fmol for C6 glioma cells. Biodistribution studies in rats suggested the excretion via kidneys and partially through the hepatobiliary route. The effective dose of [177Lu]Lu-DOTAGA-IAC was found to be 0.17 mSv/MBq. The dynamic study in patients revealed the optimal imaging time to be 30-35 mins postadministration. Out of the cohort, [68Ga]Ga-DOTAGA-IAC detected the primary lesions in all five patients with a mean standard uptake value (SUVmax) of 3.94 ± 0.58 compared with [18F]FDG (SUVmax 13.8 ± 6.53). Conclusion: The study demonstrates that DOTAGA-IAC exhibits strong binding to αVß3 integrin, positioning it as a promising PET agent for assessing primary and metastatic cancers. The outcomes from the pilot study suggest the potential of [68Ga]Ga-DOTAGA-IAC PET/CT in breast carcinoma diagnosis. While recognizing the theranostic potential of DOTAGA-IAC for αVß3 integrin-expressing tumors, further clinical investigations are warranted to comprehensively assess therapeutic efficacy.

2.
Clin Nucl Med ; 49(4): e170-e171, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38377367

RESUMO

ABSTRACT: Hepatocellular carcinoma (HCC) is an aggressive malignancy with a poor prognosis. Surgical resection is limited. Selective intra-arterial radionuclide therapy (SIRT) emerged as a potential cure for intermediate HCC with portal vein thrombosis. We report a pilot study of a 48-year-old man with recurrent HCC who underwent 177 Lu-microsphere SIRT (2.2 GBq) in segment III. Posttherapy SPECT/CT images (24 hours to 3 months) demonstrated excellent localization and prolonged retention within the tumor. Pre- and 3-month post-SIRT CECT showed a notable decrease in arterial enhancement and tumor size. Time-activity curve of the standard and the lesion demonstrated similar decay pattern indicating that 177 Lu-microspheres act as permanent implant.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Lutécio , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Microesferas , Projetos Piloto , Radioisótopos
3.
Acad Radiol ; 31(6): 2521-2535, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38233261

RESUMO

RATIONALE AND OBJECTIVES: Fibroblast Activation Protein (FAP) expressing cancer-associated fibroblasts has been a major breakthrough causing a paradigm shift in targeted theranostics focusing on the tumor microenvironment. In this study, a squaric acid derivative DOTA.SA.FAPi (SA.FAPi) has been evaluated as a potential diagnostic probe in diverse epithelial cancers and compared to the standard-of-care 18F-FDG. METHODS: 25 patients enrolled in this prospective study underwent 18F-FDG and 68Ga-SA.FAPi PET scans on two different days. For biodistribution, standardized uptake values (SUV) were computed by delineating region-of-interest on various body organs. For comparative analysis in disease identification, lesion tracer uptake was quantified using SUVs corrected for lean body mass (SUL), SUVmax, tumor-to-background ratio (TBR) with liver and blood pool as the reference, total lesion glycolysis (TLG for 18F-FDG) and total lesion FAP expression (TLF for 68Ga-SA.FAPi). RESULTS: 25 patients (mean age: 58 ± 8 years) with four types of cancers including hepatocellular carcinoma (HCC, 56% of cohort), gall bladder carcinoma (GB Ca, 12%), adrenocortical carcinoma (ACC, 16%), and breast carcinoma (breast Ca, 16%) were prospectively evaluated. Physiological tracer uptake of 68Ga-SA.FAPi was noted in the salivary glands, thyroid, liver, pancreas, muscles and kidneys with variable uptake in the lacrimal glands, extra-ocular muscles, oral mucosa and uterus. Lesion-based comparative analysis between both the radiotracers demonstrated complete concordant findings in detection of all primary lesions and distant metastases in liver, bones, adrenals and peritoneum whereas discordant findings were noted in lung nodules (20%) and lymph nodes (13%). In overall analysis, 68Ga-SA.FAPi exhibited significantly higher SUVmax (10.3 vs 8.8, p-0.019), SULpeak (6.8 vs 4.9, p-0.000) and SULavg (5.4 vs 4.1, p-0.019) in comparison to 18F-FDG whereas TBR was comparable for both the tracers [TBRLiver: median 1.9 (IQR: 2.6-1.4) vs 1.8 (2.6-1.1), p-0.275; TBRBloodpool: 2.1 (3.7-1.4) vs 2.0 (2.7-1.4), p-0.207]. In subcategorical analysis, 68Ga-SA.FAPi demonstrated higher SUVmax, SULpeak and SULavg values for primary disease (SUVmax: 14.8 (18.7-9.7) vs (12.9-6.6), p-0.087; SULpeak: 8.2 (11.2-6.8) vs 6.3 (8.5-4.4), p-0.037; SULavg: 6.9 ± 2.5 vs 5.1 ± 2.2, p-0.023] and distant metastases (8.8 vs 7.2, p-0.038); 6.3 (8.8-4.4) vs 3.6 (4.4-2.0), p-0.000; 5.4 vs 3.5, p-0.000] whereas comparable values were noted for both the tracers in nodal metastases [9 (13.5-4.1) vs 8 (12.7-4.7), p-0.726; 4.5 (6.2-1.8) vs 4.3 (5.7-2.2), p-0.727; 4.1 ± 2.3 vs 3.7 ± 1.8, p-0.129]. In primary disease, highest 68Ga-SA.FAPi avidity was noted in ACC followed by GB Ca and HCC. In distant metastases, gall bladder, lung and skeletal lesions demonstrated higher 68Ga-SA.FAPi avidity. Moreover, 68Ga-SA.FAPi identified five additional lung lesions which were missed by 18F-FDG in one case of ACC. CONCLUSION: 68Ga-SA.FAPi emerged as an effective, versatile diagnostic probe for imaging various epithelial malignancies similar to 18F-FDG.


Assuntos
Fluordesoxiglucose F18 , Compostos Radiofarmacêuticos , Humanos , Feminino , Masculino , Fluordesoxiglucose F18/farmacocinética , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Estudos Prospectivos , Idoso , Compostos Organometálicos/farmacocinética , Neoplasias Epiteliais e Glandulares/diagnóstico por imagem , Radioisótopos de Gálio , Adulto , Tomografia por Emissão de Pósitrons/métodos , Distribuição Tecidual , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Quinolinas
4.
J Nucl Cardiol ; 30(5): 1782-1793, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36849635

RESUMO

BACKGROUND: Soft-tissue attenuation remains a major limitation of SPECT-MPI which interferes with the diagnosis of CAD. The current study aims to evaluate the pattern of attenuation artifacts in supine and semi-reclining positions on CZT cardiac camera and their interaction with gender, BMI and stress protocols. METHODS: We prospectively analysed 150 patients acquired in supine and semi-reclining positions on CZT camera. The images were evaluated for severity and extent of defect using 17-segment model. An additional CT scan was acquired to generate AC image in the first 50 patients studied to assist investigator learning for comparison of artifact vs true defects in the two SPECT systems. The defects present in one position or showing change in severity within two positions were considered as positional artifacts and further validated using CTAC supine image. RESULTS: In overall analysis, higher extent and severity of positional artifacts were observed more in semi-reclining position affecting the apex, apico-inferior, inferolateral and inferoseptal segments. Females showed more positional artifacts than males with inferior wall attenuation in the semireclining position and anterior wall attenuation in the supine position. A positive correlation of the extent and severity of positional artifacts was noted with an increasing BMI. In patients with BMI > 30, mid inferior and inferolateral segments were most affected followed by anterior wall segments. Highest correction of artifactual perfusion defects by CTAC was noted in inferior wall followed by inferolateral segments. CONCLUSION: The incidence of positional artifacts was greater in semi-reclining position in females, higher BMI groups and adenosine stress subsets. Knowledge of the pattern of positional artifacts appears to be a reliable alternative of CTAC for correct interpretation of myocardial perfusion images.


Assuntos
Imagem de Perfusão do Miocárdio , Masculino , Feminino , Humanos , Imagem de Perfusão do Miocárdio/métodos , Artefatos , Processamento de Imagem Assistida por Computador , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios X/métodos , Decúbito Dorsal
5.
Clin Nucl Med ; 48(4): e173-e175, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36727882

RESUMO

ABSTRACT: Metastatic or recurrent adrenocortical carcinoma (ACC) is a potentially fatal malignancy, which poses major challenges in disease management owing to lack of effective systemic therapies. The drastically reduced survival rates require prompt identification of selective molecules for development of targeted therapeutics. We evaluated the squaric acid containing FAPI derivative, DOTA.SA.FAPI (FAPI), as a potential diagnostic probe in 2 cases of histopathologically proven metastatic and recurrent ACC. Both patients underwent 18 F-FDG and 68 Ga-FAPI PET/CT scans for comparative analysis. 68 Ga-DOTA.SA.FAPI emerged as an excellent diagnostic agent for ACC and performed similar to 18 F-FDG.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Humanos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
6.
Clin Nucl Med ; 48(2): e95-e98, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36607383

RESUMO

ABSTRACT: Adrenocortical carcinoma (ACC) is a rare malignancy with a prevalence of 1 to 2 cases/million/year. The diagnosis depends upon endocrine workup followed by imaging with CT, MRI, and 18F-FDG PET/CT. The treatment includes surgical resection, debulking surgery, chemotherapy, and radiotherapy. However, patients do not respond well to any of the available therapies. We present noninvasive imaging of histopathology-proven ACC patients using 68Ga-DOTAGA-IAC PET/CT, specific for integrin αvß3. 68Ga-DOTAGA-IAC PET/CT 45 minutes after IV injection showed a decent tumor-to-background ratio and could be used as a promising radiotracer for metastatic and recurrent ACC.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Carcinoma Adrenocortical/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Neoplasias do Córtex Suprarrenal/patologia , Fluordesoxiglucose F18
7.
Transl Oncol ; 15(1): 101295, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34847420

RESUMO

Radioligand therapies have opened new treatment avenues for cancer patients. They offer precise tumor targeting with a favorable efficacy-to-toxicity profile. Specifically, the kidneys, once regarded as the critical organ for radiation toxicity, also show excellent tolerance to radiation doses as high as 50-60 Gy in selected cases. However, the number of nephrons that form the structural and functional units of the kidney is determined before birth and is fixed. Thus, loss of nephrons secondary to any injury may lead to an irreversible decline in renal function over time. Our primary understanding of radiation-induced nephropathy is derived from the effects of external beam radiation on the renal tissue. With the growing adoption of radionuclide therapies, considerable evidence has been gained with regard to the occurrence of renal toxicity and its associated risk factors. In this review, we discuss the radionuclide therapies associated with the risk of nephrotoxicity, the present understanding of the factors and mechanisms that contribute to renal injury, and the current and potential methods for preventing, identifying, and managing nephrotoxicity, specifically acute onset nephropathies.

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