Tc-99m ciprofloxacin imaging in diagnosis of chronic bacterial prostatitis

Ji-Kan Ryu¹, Seong-Min Lee¹, Do-Whan Seong¹, Jun-Kyu Suh¹, Sungeun Kim², Wonsick Choe², Yeonsook Moon³, Soo-Hwan Pai³

¹Department of Urology ,²Department of Nuclear Medicine, ³Department of Clinical Patholgy, Inha University School of Medicine, Incheon 400103, Korea

Keywords: prostate; prostatitis; pelvic pain syndrome; urinary tract infections; radioisotope diagnostic techniques

Abstract

Aim: To investigate the value of Tc-99m ciprofloxacin imaging in the differential diagnosis of chronic bacterial prostatitis. Methods: The study included 4 normal subjects as the negative controls, 2 patients with acute prostatitis or cystourethritis as the positive controls and 59 patients diagnosed as chronic bacterial prostatitis or chronic pelvic pain syndrome by traditional laboratory tests. In every subject, the single photon emission computerized tomography images were obtained 3 h after intravenous injection of Tc-99m Ciprofloxacin. The results of the imaging were compared with those of laboratory tests. Results: On the images, negative uptake was observed in all normal subjects, while strong hot uptake, in the whole prostate of acute prostatitis patients and in the whole urethra of acute cystourethritis patients. In 13 (68 %) of 19 patients categorized as chronic bacterial prostatitis by standard laboratory tests, hot uptake with less intensity than that of acute prostatitis was observed in the prostate area around the prostatic urethra. Negative uptake in the prostate was observed in 6 of 19 patients (32 %) categorized as chronic bacterial prostatitis. Interestingly, hot uptake in the prostate was exhibited in 28 (70 %) of the 40 patients categorized as chronic pelvic pain syndrome. Conclusion: Tc-99m ciprofloxacin imaging is helpful in the differential diagnosis of prostatitis syndrome.

1 Introduction

Prostatitis syndrome is the most common urologic problem in men less than 50 years old and about half of all men suffer from the syndrome at certain points of their lives [1, 2]. Accurate diagnosis of prostatitis syndrome represents a major challenge for clinicians and microbiology laboratories. Lower urinary tract localization study represents the "golden standard" for the diagnostic evaluation of prostatitis syndrome [1, 3]. Tradi-tionally, the prostatitis syndrome has been classified into acute bacterial prostatitis, chronic bacterial prostatitis and chronic pelvic pain syndrome by the 4-category test [4]. However, a culture for prostatic secretion frequently reveals a false-positive result due to microbial contamination or a false-negative one as the prostatic infection is a focal process and sampling errors are inevitable. There-fore, this method often cannot identify prostatic infection accurately. Moreover, it is not infrequent that clinicians empirically use antibiotics without definite evidence of infection [5, 6].

Tc-99m ciprofloxacin scintigraphy, first introduced by Solanki et al. [7], has been reported to visualize the focus of bacterial infection, as it claims to show an area with viable and proliferating bacterial population that is actively using DNA gyrase, which ciprofloxacin will inhibit. Therefore, it has been tried in various infectious conditions [8-11] and found to be very useful to differentiate infection from inflammation. We have indicated that with Tc-99m ciprofloxacin imaging, it is possible to identify bacterial prostatits [12]. Herein, we first investigated the value of Tc-99m ciprofloxacin imaging for the differential diagnosis of chronic bacterial prostatitis in patients with prostatitis syndrome.

2 Materials and methods

The study included 4 healthy controls without a history of prostatitis or lower urinary tract infection symptoms, 1 cystourethritis patient and 60 patients [mean age: (42.4 10.9) years, range: (23-69) years] with prostatitis syndrome for more than 3 months. None had taken antimicrobial agents for at least 6 weeks.

2.2 Clinical evaluation

Written informed consent was obtained from all patients. Following a standard history and physical examination, subjects were evaluated by the same physician for routine bacteriological localization study as described by Meares and Stamey [13]. The urethral urine, midstream bladder urine, expressed prostatic secretion and post-massage urine or semen were collected, examined microscopically and cultured for both gram positive and negative aerobes. To identify Mycoplasma hominis and Ureaplasma urealyticum, Mycofast^® kit (International Microbio, France) was used. DNA detection of Chlamydia trachomatis was performed by polymerase chain reaction test using Gen-Probe Pace 2 system^® . Based on the NIH classification system, those with established uropathogens localized to the expressed prostatic secretion were classified as having category II and those without localizing pathogens, as category III prostatitits, which was subclassified according to the wet mount microscopy of expressed prostatic secretion or seminal fluid as categories IIIa and IIIb (with>=10 and <10 white blood cells per high power field, respectively).

We formulated a Tc-99m ciprofloxacin kit. Cipro-floxacin 2 mg were dissolved in stannous tartrate (as a reducing agent) in a 10 mL sterile vial with shaking for 2 minutes to 3 minutes. Fifteen mCi of Tc-99m were added to the vial, incubated for 30 min at room temperature and to each patient, 5 mL of the prepared radiopharmaceutical was injected intravenously.

In every subject, the single photon emission computerized tomography (SPECT) images were obtained 3 h after 15 mCi Tc-99m ciprofloxacin intravenous injection. A Siemens gamma camera was used with a LEAP (low-energy-all-purpose) collimator. The matrix size was 128 128 and a Butterworth filter and filtered-back-projection (FBP) for reconstruction were used. In a patient with acute bacterial prostatitis, magnetic resonance imaging (MRI) of prostate was additionally performed. Nuclear images were interpreted by a nuclear medicine specialist. They were read blindly without knowing the microbilogical results. It was regarded as positive when the imaging showed an area of abnormally high uptake of the radioisotope in the prostate gland compared with the finding in control subjects. These results were compared to those by standard microbiological tests.

3 Results

Of the 60 patients with prostatitis syndromes, one patient was diagnosed as acute bacterial prostatitis (Category I), 19 as chronic bacterial prostatitis (Category II) and 40 as chronic pelvic pain syndrome (category IIIa: 24 cases; category IIIb: 16 cases) on the basis of standard 4-catagory test.

The results of prostate imaging for these patients were summarized in Table 1. Radiolabelling efficiency was more than 95 % and no bone marrow uptake was seen. With Tc-99m ciprofloxacin scintigraphic imaging, no isotope uptake was shown at the prostate in all the normal subjects (Figure 1). An acute cystourethritis patient showed hot uptake at the entire urethra, but not the prostate (Figure 2). Images of an acute bacterial prostatitis patient also revealed an area of strong hot uptake in the area corresponding to the prostate. Pelvic MRI in this patient showed findings compatible with acute prostatic infection (Figure 3).

Figure 1. Tc-99m ciprofloxacin image of a control subject without prostatitis syndrome. There is no increased uptake at the prostate site (arrow).

Figure 2. Tc-99m ciprofloxacin image of an acute cystourethritis patiens with increased uptake at the urethra (arrow), but not at the prostate (asterisk).

Figure 3. A. Tc-99m ciprofloxacin image of an acute symptomatic prostatitis patient with an area of increased uptake (arrow) at the prostate site. B. Magnetic resonance image of the same patient. The prostate is enlarged with multiple foci of micro-abscesses.

Table 1. Results of Tc-99m ciprofloxacin imaging in patients with prostatitis syndrome. Category I: acute bacterial prostatitis, Category II: chronic bacterial prostatitis; Category IIIa: chronic pelvic pain syndrome, inflammatory type; Category IIIb: chronic pelvic pain syndrome, non-inflammatory type.

Thirteen (68 %) of 19 chronic bacterial prostatitis patients classified by standard laboratory tests showed hot uptake at the prostate, while the remaining 6 (32 %), no uptake. Of the 40 patients with chronic pelvic pain syndrome, 28 (70 %) showed hot uptake at the prostate. Typical pattern of the prostatic imaging suggesting chronic bacterial prostatitis is shown as hot uptake with less intensity than that of acute bacterial prostatitis and usually distributed around the prostatic urethra.

The results of prostate imaging with respect to the isolated organisms were shown in Table 2. The most common causative organisms in these patients were Staphylococcus, followed by Ureaplasma urealyticum, Streptococcus and Chlamydia trachomatis.

Table 2. Results of Tc-99m ciprofloxacin imaging in accordance with organisms isolated in patients diagnosed as chronic bacterial prostatitis by traditional laboratory tests.

Prostatitis encompasses a heterogenous group of infectious and noninfectious disorders, most of which are not sufficiently evaluated with regard to the determination of their causes [14, 15]. The classification system to categorize prostatitis syndrome has been established, but often proved to be unreliable in clinical practice.

Patients with chronic prostatitis symptoms are more likely to have prostatic inflammation compared to asymptomatic controls, but in bacteriologic tests both may show similar results [16]. Moreover, in physical examination and with respect to the response to antimicrobial agents and prognosis, patients with chronic bacterial prostatitis and chronic pelvic pain syndrome may have similar findings [5].

Although many organisms have been associated with these syndromes, it is exceedingly difficult for most sophisticated laboratories to provide conclusive results even with optimal clinical samples. Tc-99m ciprofloxacin imaging has been reported to be of great value to differentiate infection from inflammation in various infectious conditions, such as osteomyelitis, soft tissue infection, lung abscess, pelvic inflammatory disease and renal infection [8-11]. It is controversial whether neutrophils and activated macrophages can take up ciprofloxacin [17]. However, it is not likely to be an important problem in imaging, since it has been shown that Tc-99m cipro-floxacin is taken up only by bacterial but not sterile abscess and WBCs exhibit either no or negligible uptake[8]. We are also aware of the ongoing debate that is mainly on the musculoskeletal infection [18].

The reported overall sensitivity and specificity of Tc-99m ciprofloxacin imaging were 85.5 % and 82.3 %, respectively [19]. In this study, 13 (68 %) of 19 patients with chronic bacterial prostatits and 28 (70 %) of 40 patients with chronic pelvic pain syndrome classified by standard microbiological method showed positive uptake of radioisotope in prostate imaging. Interestingly, our results may reflect that the prevalence of chronic bacterial prostatitis is much higher than expected. Moreover, many authors suggest that conventional 4-glass test may have high false-negative results, which potentially result from inappropriate prostatic massage, prostatic duct obstruction, focal distribution of the infection, previous or current antibiotic treatment, limitation of laboratory tests to identify microorganisms, etc. This may indicate that many patients with chronic pelvic pain syndrome as classified by laboratory tests have actual microbial infection in the prostate gland and that these patients may respond well to antimicrobial agents.

In this study, about one third (32 %) of patients with positive culture of prostatic secretion showed no uptake of the isotope in prostate imaging. This kind of false-negative results may be due to previous antibiotic therapy and/or infection with organisms that do not take up Tc-99m ciprofloxacin. Thus, a negative result in prostate imaging does not rule out the infection. Collection of prostatic secretion may sometimes be contaminated with microorganism from urethra or glans. Moreover, it is also likely that some positive microbial culture may be the result of infection from some other source, such as the seminal vesicle.

We indicated that Staphylococcus species, Urea-plasma species, Streptococcus species and Chlamydia species were frequently associated with chronic bacterial prostatitis and many of them also showed positive uptake of isotope in the imaging. Our results suggested that gram-positive cocci, including Staphylococci may play an important role in the pathogenesis of chronic bacterial prostatitis, although the role of those organisms as commensal organisms or pathogens was controversial [14, 20].

Although it is true that a strong bladder uptake interferes with the surrounding structures in the same visual field, the image was still readable. The new or better reconstruction algorithm that is unfortunately not available to us may help in the future.

The major limitation of Tc-99m ciprofloxacin imaging in the diagnosis of chronic bacterial prostatitis is that we do not precisely know its diagnostic accuracy, including its sensitivity and specificity. Prospective studies are going on to further validate this imaging method.

In conclusion, Tc-99m ciprofloxacin imaging is useful to discriminate chronic bacterial prostatitis that is not diagnosed with ease by standard laboratory tests.

This work was supported by INHA UNIVERSITY Research Grant (INHA-30317).

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Correspondence to: Wonsick Choe, M.D., Department of Nuclear Medicine, Inha University Hospital, 7-206 3rd ST., Sinheung-Dong, Jung-Gu, Incheon 400-103, Korea.
Tel: +82-32-890 3160, Fax: +82-32-890 3164
E-mail: wchoe@inha.ac.kr
Received 2003-06-05  Accepted 2003-07-17

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