Febrile renal transplant recipient with discordant findings of (99m)Tc-Leukoscan (Sulesomab) and (67)Ga-citrate scan in pyelonephritis.

Nuclear medicine techniques like (99m)Tc-Leukoscan and (67)Ga-citrate scan have been used in localizing infectious pathologies in renal transplant patients. We present an interesting case of febrile renal transplant with discordant findings of tracer uptake in the transplant kidney on (99m)Tc-Leukoscan and (67)Ga-citrate scan.

INTRODUCTION

67Ga-citrate scan is commonly used to localize soft tissue infectious foci. It is a non-specific tracer that localises at sites of infection and inflammation. 99mTc-leukoscan is also used as a specific imaging tool for infection imaging. We present a case of febrile renal transplant that showed discordant findings on 67Ga-citrate scan and 99mTc-leukoscan. These investigations act in a complementary manner and help in accurately defining sites of infection.

CASE REPORT

Single 19-year-old male, a renal transplant recipient presented with history of fever with gradual rise in the white blood counts (WBC) and serum creatinine over 2 months. The patient underwent pre-emptive renal transplant a year ago as he was diagnosed to have chronic kidney disease with bilateral reflux nephropathy. Post-renal transplant the patient was on regular immunosuppressant therapy with steroids for 10 months, he started having episodes of febrile illness since 2 months. Patient developed complications of miliary tuberculosis with recurrent secondary evidence of pseudomonal urinary tract infection for which apart from steroids, immunosuppressants, he was started on AKT (Anti-tubercular medication containing ethambutol 500mg, isoniazid 300mg, pyrazinamide 750mg and rifampicin 450mg), antibiotics and antihypertensives. On examination there was tenderness in right loin. The ultrasound revealed unremarkable both native kidneys and normal sized transplant kidney with prominent cortices. Blood investigations revealed raised WBC, normal biochemistry tests, marginally raised cyclosporine levels, Cytomegalo Virus (CMV) was negative. Urine routine examinations revealed 15-20 pus cells and urine culture showed rich growth of pseudomonas aeruginosa.

A dose of 740 MBq (20 mCi) of 99mTc-Sulesomab (99mTc-Leukoscan) was injected intravenously and planar early as well as delayed whole body images were acquired in anterior and posterior projections at 2 h and 24 h respectively. Following this a dose of 148 MBq (4mCi) of 67Ga-Citrate was injected intravenously and planar whole body anterior and posterior images were acquired at 48 h.

99mTc-Leukoscan [Figure 1] revealed the transplant renal graft located in the right iliac fossa, appears normal in size and reveals inhomogeneous radiotracer uptake. It revealed relatively reduced radiotracer uptake in the upper pole (two areas) and in the lower pole (single area) with normal physiological uptake in the midpole region (functioning renal parenchyma revealing normal excretory phase). There is a faint visualization of the native right kidney in the 2 h and 24 h images. The native left kidney is not visualized throughout the study. Normal biodistribution of 99mTc-Sulesomab is seen in salivary glands, liver, spleen, blood pool, bone marrow, bladder and gut.

Figure 1

Wholebody anterior and posterior images acquired at 2 h and 24 h post-injection of 740 MBq of 99mTc-leukoscan, scan findings of areas of relatively reduced radiotracer uptake seen involving the upper pole (two) and lower pole (one) of transplant kidney and the faint visualization of the native right kidney

67Ga-Citrate scintigraphy [Figure 2] acquired at 48 h revealed abnormal diffuse accumulation of tracer in the native right kidney and two focal areas of increased tracer uptake involving the upper pole and a focal area of tracer uptake in the lower pole of the transplanted kidney (corresponding to the relatively reduced radiotracer uptake areas seen on 99mTc-Leukoscan).

Figure 2

Wholebody anterior and posterior images acquired at 48 h post-injection of 148 MBq 67Ga-Citrate, scan findings of areas of increased radiotracer uptake seen involving the superior pole (two) and inferior pole (one) of transplant kidney and the faint visualization of the native right kidney suggestive of pyelonephritic involvement

This report shows diffuse pyelonephritic involvement of the native right kidney, the upper and lower poles of transplant kidney revealing discordance in uptake in 99mTc-leukoscan and 67Ga-Citrate scan in the transplant kidney.

DISCUSSION

99mTc-anti-NCA (Nonspecific cross-reacting antigen) -90 Fab’ (LeukoScan) antigranulocyte antibody and 67Ga-citrate are approved radiopharmaceuticals for imaging inflammation/infection.[1] 99mTc-Sulesomab (LeukoScan) and Gallium-67 scanning (one of the comparators) both require a single injection.[2] Neither of these procedures requires blood handling.[2] 67Ga-citrate due to its physical characteristics (multiple photons energy; long half life) and binding to the plasma protein transferrin (resulting in relatively high background and therefore reduced lesion-to-background contrast), it was less than ideal as an imaging agent.[1] Wolfgang Becker, et al., concluded that immunoscintigraphy with 99mTc-NCA-QO Fab’ fragments offers rapid localization of foci, rapid and simple use, a negligible HAMA (Human anti-mouse antibody) response rate, no effect on granulocyte function and an accuracy comparable to WBC scanning.[2] It is approved for the imaging of infections and inflammations in patients with suspected osteomyelitis,[3] and is being investigated for other purposes like the detection of soft tissue infections.[4] The study of Skehan, et al., elucidated some important points: The monoclonal Fab’ antibody of 99mTc-sulesomab does not significantly bind to circulating quiescent granulocytes (<5% binding).[5] Despite specific binding of 99mTc-sulesomab to primed and activated granulocytes in the infectious site, the prevalent mechanism of 99mTc-sulesomab accumulation is related simply to the non-specific increase of capillary permeability.[5] In our case report, the transplant kidney revealed relatively reduced leukoscan uptake in the superior and inferior poles, decreased radiotracer uptake at abnormal site compared to the rest of the kidney could be secondary to non-specific increase of capillary permeability and thereby washout of leukoscan tracer from pyelonephritic involvement site. Gallium scan revealed discordance of tracer uptake than seen on the leukoscan.

The risk of infections is not significantly increased in patients with normoglycaemia.[6] Vice versa, severe infections lead to increased secretion of stress hormones such as cortisol, catecholamines, glucagon and growth hormone and to insulin resistance, thereby aggravating glycaemic control.[6-8] Finally, a vicious circle ensues, in which infections aggravate hyperglycaemia, which, in turn, perpetuates the susceptibility to infections.[6-8] In our case the patient was non-diabetic young post-renal transplant recipient on immunosuppressants thereby suppressing the immune system and increasing patients susceptibility to infections. In our patient scans revealed pyelonephritic involvement at three distinct areas in the transplant kidney and in native right kidney.

In a recent prospective study by Rubello, et al,[9] the protocol used was early (4 h) and delayed (24 h) acquisition of 99mTc-sulesomab images. Specifically, a pattern of increasing uptake was judged as infection (true-positive result), whereas a pattern of decreasing uptake was judged as non-specific early accumulation (false-positive result).[9] By adopting these interpretation criteria, they obtained a significantly improved specificity for the 99mTc-sulesomab examination 75% versus 87.5% in patients with diabetic foot infection and 76.2% versus 85.7% in patients with other peripheral bone infections or prosthetic joints.[9] The Fab’ fragment is directed against NCA-90, a homotypic adhesion molecule.[10] The sensitivity of immunoscintigraphy in the study with small patient series was 88%. This compares well to the 80% sensitivity reported for 67Ga,[11] 99mTc-nanocolloids[12] at 93%, 111ln-oxine granulocytes at 93% in the diagnosis of peripheral osteomyelitis[13] and 111In-HIG (Human polyclonal immunoglobulin G) at 86% in the diabetic foot with infection.[14] Specificity of 67Ga has been reported to be 83%; 99mTc-nanocolloid has been 88%;[12] 111ln-oxine labeled granulocytes has been 85%;[13] and 111In-HIG has been 84%[14] in the diagnosis of osteomyelitis.

Patients with acute pyelonephritis may present with a spectrum of clinical signs and symptoms. There are few non-invasive diagnostic studies, however, to confirm or exclude this diagnosis.[15] A small number of patients, generally those with severe disease, will demonstrate radiographic changes on excretory urography, but the lack of sensitivity of the IVP (Intravenous pyelography) in early, acute pyelonephritis is well documented.[15] Several radionuclide techniques have been proposed to assist in the earlier detection of this clinical problem including imaging with Mercury-197 chlormerodrin, Gallium-67 citrate, Technetium-99m glucoheptonate, Technetium-99m DMSA (Dimercapto Succinic acid), and more recently, Indium-111 labeled white blood cells.[15] There appears to be a complimentary role for the cortical imaging agents and the radiopharmaceuticals which localize in bacterial infection.[15] Cortical agents offer the advantage of specific assessment of functioning renal tissue and a convenient, rapid method for following the response to treatment in a non-invasive manner.[15] A pattern is described which may be diagnostic; correlation with Gallium-67 citrate or Indium-111 WBCs may increase the probability of infection as the cause for the cortical abnormality.[15]