Potential role of ¹²⁴I-girentuximab in the presurgical diagnosis of clear-cell renal cell cancer

Figures & data

Figure 1 Computed tomography (CT) appearance of small right posterior renal tumor (A1) and corresponding ¹⁸F-fluoro-d-glucose positron emission tomography (¹⁸F-FDG-PET) (A2) and fused PET low-dose noncontrast CT (A3) images demonstrating FDG uptake. Please note mild right renal uptake related to tracer excretion in the collecting system. In contrast, a 12.5 cm anterior right renal mass clearly visualized on contrast-enhanced CT (B1) that demonstrated minimal to no FDG uptake and was falsely considered benign on PET and fused images (B2 and B3).

Note: These images highlight the lack of sensitivity that has limited the clinical applicability of ¹⁸F-FDG-PET in the management of localized renal cell carcinoma.

Figure 2 The Von Hippel–Lindau/hypoxia-inducible factor oxygen-sensing pathway and its relevance in clear-cell renal cell carcinoma.

Note: Copyright © 2010, Elsevier. Reproduced with permission from Stillebroer AB, Mulders PF, Boerman OC, Oyen WJ, Oosterwijk E. Carbonic anhydrase IX in renal cell carcinoma: implications for prognosis, diagnosis, and therapy. Eur Urol. 2010;58(1):75–83.⁸¹
Abbreviations: PHD, prolyl 4-hydroxylase domain; HIF, hypoxia-inducible factor; VHL, Von Hippel–Lindau; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor; CAIX, carbonic anhydrase IX.

Table 1 Renal cell carcinoma-directed imaging using radiolabeled G250

Study	Year	Trial design	Primary outcomes	Patients n (n final)	Imaging agent	RCC stage	Accuracy (primary/mRCC)	Adverse events†
Oosterwijk et al^Citation91	1993	I*	Imaging and biodistribution characteristics	16 (15)	^131I-mG250	All	12/12 ccRCC 1/3 non-ccRCC >90% of primary and mRCC lesions	None
Steffens et al^Citation79	1997	I*	Pharmacokinetics, biodistribution, immunogenicity, and imaging characteristics	16	^131I-cG250	All	13/13 ccRCC 0/3 non-ccRCC 5/5 mRCC	HACA 2/16
Divgi et al^Citation78	1998	I/II	Maximum tolerated dose and therapeutic efficacy (RIT)	33	^131I-mG250	IV	100% lesions > 2 cm	None
Steffens et al^Citation99	1999	I	Maximum tolerated dose (RIT)	12	^131I-cG250	IV	Metastases visualized in 9/12 patients	None
Brouwers et al^Citation92	2002	Open, nonrandomized	Diagnostic efficacy (intrapatient comparison)	20	^131I-cG250 vs ^18F-FDG	IV	Metastases visualized in 77/112 ^18F-FDG 34/112 ^131I-cG250	None
Brouwers et al^Citation95	2003	Subanalysis of phase I/II trial	Diagnostic efficacy (intrapatient comparison)	5	^131I-cG250 vs ^111In-cG250	IV	^111In-cG250 47 lesions ^131I-cG250 30 lesions	None
Divgi et al^Citation100	2004	I	Maximum tolerated dose (fractionated RIT)	15	^131I-cG250	IV	100% lesions > 2 cm	2/15 HACA 1/15 G2 allergic reaction
Brouwers et al^Citation94	2005	I/II	Safety and therapeutic efficacy (RIT)	29	^131I-cG250	IV	CT/MRI 92 lesions ^131I-cG250 138 lesions	None
Divgi et al^Citation20	2007	I*	Characterization of tumor histology	26 (25)	^124I-cG250	All	15/16 ccRCC 0/9 non-ccRCC Sensitivity 94% NPV 90%, PPV 100%	None
Uzzo et al^Citation108	2010	III*	Characterization of tumor histology, comparison of diagnostic efficacy with CECT	204 (195)	^124I-cG250	All	86% sensitivity 87% specificity 95% PPV	13.3% transient AEs 1/204 G3 hepatic dysfunction 56/198 HACA

Notes:

* Presurgical imaging;

† only adverse events related to the use of G250 for diagnostic or pretreatment purposes were reported.

Abbreviations: RCC, renal cell carcinoma; ccRCC, clear-cell RCC; mRCC, metastatic RCC; m, murine; c, chimeric; HACA, human antichimeric antibodies; CECT, contrast-enhanced computed tomography; RIT, radioimmunotherapy; G, grade; NPV, negative predictive value; PPV, positive predictive value; AE, adverse event.

Figure 3 A 71-year-old female who presented with an incidentally diagnosed, enhancing 4 cm right renal mass (A), which demonstrated positive uptake on ¹²⁴I-girentuximab (G250) positron emission tomography/computed tomography (B); pathology following open partial nephrectomy revealed pathologic stage T1b Nx Mx clear cell renal cell carcinoma.

Note: Copyright © 2011, Elsevier. Reproduced with permission from Smaldone MC, Chen DY, Uzzo RG, Yu M. Molecular imaging of the small renal mass. Urol Oncol. 2011;29(6):589–592.⁵⁵

StillebroerABMuldersPFBoermanOCOyenWJOosterwijkECarbonic anhydrase IX in renal cell carcinoma: implications for prognosis, diagnosis, and therapyEur Urol2010581758320359812

 PubMed Web of Science ®Google Scholar

OosterwijkEBanderNHDivgiCRAntibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250J Clin Oncol19931147387508478666

 PubMed Web of Science ®Google Scholar

SteffensMGBoermanOCOosterwijk-WakkaJCTargeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250J Clin Oncol1997154152915379193349

 PubMed Web of Science ®Google Scholar

DivgiCRBanderNHScottAMPhase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinomaClin Cancer Res1998411272927399829736

 PubMed Web of Science ®Google Scholar

SteffensMGBoermanOCde MulderPHPhase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250Clin Cancer Res19995Suppl 103268s3274s10541374

 PubMed Web of Science ®Google Scholar

BrouwersAHDorrULangO131 I-cG250 monoclonal antibody immunoscintigraphy versus [18 F]FDG-PET imaging in patients with metastatic renal cell carcinoma: a comparative studyNucl Med Commun200223322923611891480

 PubMed Web of Science ®Google Scholar

BrouwersAHBuijsWCOosterwijkETargeting of metastatic renal cell carcinoma with the chimeric monoclonal antibody G250 labeled with (131)I or (111)In: an intrapatient comparisonClin Cancer Res2003910 Pt 23953S3960S14506194

 PubMed Web of Science ®Google Scholar

DivgiCRO’DonoghueJAWeltSPhase I clinical trial with fractionated radioimmunotherapy using 131I-labeled chimeric G250 in metastatic renal cancerJ Nucl Med20044581412142115299069

 PubMed Web of Science ®Google Scholar

BrouwersAHMuldersPFde MulderPHLack of efficacy of two consecutive treatments of radioimmunotherapy with 131I-cG250 in patients with metastasized clear cell renal cell carcinomaJ Clin Oncol200523276540654816170161

 PubMed Web of Science ®Google Scholar

DivgiCRPandit-TaskarNJungbluthAAPreoperative characterisation of clear-cell renal carcinoma using iodine-124-labelled antibody chimeric G250 (124I-cG250) and PET in patients with renal masses: a phase I trialLancet Oncol20078430431017395103

 PubMed Web of Science ®Google Scholar

UzzoRGRussoPChenDThe multicenter phase III Redect trial: a comparative study of 124 I-girentuximab-PET/CT versus diagnostic CT for the pre-operative diagnosis of clear cell renal cell carcinoma (ccRCC) [late-breaking abstract]AUA Annual MeetingMay 29–June 3 2010San Francisco, CA, USA

 Google Scholar

SmaldoneMCChenDYUzzoRGYuMMolecular imaging of the small renal massUrol Oncol201129658959222078404

 PubMed Web of Science ®Google Scholar