Non-invasive monitoring of photodynamic therapy with 99technetium HMPAO scintigraphy

Moore, Ronald B.; Chapman, J. D.; Mokrzanowski, A. D.; Arnfield, M.R.; McPhee, Malcolm S.; McEwan, Alexander

doi:10.1038/bjc.1992.102

Cited by 21 publications

(28 citation statements)

References 14 publications

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“…These findings are comparable to our data obtained with 5 mg kg-I, because PI1 is at least two times more active than HPD (25). Using scintigraphy with 99mTc-HMPA0, Moore et al (13) observed a light-dose-dependent shut-down in tumor perfusion following PII-PDT in rats (tumor size: 2-3 cm3). Quantitative comparison of this study with our data is difficult because most of their TVP values were determined following PDT at 2 h after drug administration, i.e.…”

Section: Discussionsupporting

confidence: 90%

“…This constraint together with the necessity to use arterial cannulation to avoid the peripheral circulation and the immediate trapping of the microspheres by the lungs, render this method difficult to apply in mice. As it was demonstrated with 99mTc-HMPA0 (13,14), 9h"T~-MIBI could be useful for the noninvasive monitoring of TVP by scintigraphy, at least in the case where the tumor size is higher than the resolution of the y-camera, which was not the case in our tumor model. These two perfusion agents have recently been compared in tumor-bearing rabbits for their potential use as tumor-imaging agents (26).…”

Section: Discussionmentioning

confidence: 69%

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Measurement of Tumor Vascular Damage in Mice with 99m Tc‐MIBI Following Photodynamic Therapy

Brasseur

Lewis

Rousseau

et al. 1996

Photochem & Photobiology

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The clinical perfusion agent 99mTc-MIBI was used to monitor changes in tumor vascular perfusion (TVP) induced by Photofrin (PII)-mediated photodynamic therapy (PDT). BALB/c mice bearing an EMT-6 tumor on each hind thigh were given an intravenous injection of 1, 2 or 5 mg kg-1 PII. Twenty-four hours later, one tumor was illuminated (600-650 nm, 200 mW cm-2, 400 J cm-2) while the other served as a control. At various time intervals after PDT (0, 2 and 24 h) mice received an intravenous injection of 99mTc-hexakismethoxyisobutylisonitrile (MIBI) (0.18 MBq g-1) and were sacrificed 2 min later. The light-treated and the untreated tumors were then dissected, the radioactivity was counted and the percentage of the injected dose per gram of tumor (%ID g-1) was calculated as a measure of TVP. We observed that TVP is drug dose dependent, develops progressively with time post-PDT and is inversely related to PDT efficacy. Our data show that early tumor retention of 99mTc-MIBI is a simple method to assess TVP and vascular damage induced by PDT.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 69%

Measurement of Tumor Vascular Damage in Mice with 99m Tc‐MIBI Following Photodynamic Therapy

Brasseur

Lewis

Rousseau

et al. 1996

Photochem & Photobiology

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“…The dual hypoxic marker technique was further investigated with Dunning R3327-AT and R3327-H tumours growing in Fischer x Copenhagen rats. The radiosensitivity, perfusion status and spontaneous and photodynamic therapy-induced hypoxia in these tumour models have been reported previously (Thorndyke et al, 1985;Chapman et al, 1991;Moore et al, 1992Moore et al, , 1993. The average radiobiological HF of R3327-AT tumours is -15%, whereas the R3327-H tumour is well perfused with no measurable HF by the radiobiological or hypoxic marker techniques (Thorndyke et al, 1985).…”

Section: Resultssupporting

confidence: 71%

“…Tumour growth was monitored twice weekly until tumours reached volumes of 5-10 cm3 as determined from three mutually perpendicular measurements of tumour diameter made with callipers (Thorndyke et al, 1985). Previous studies (Thorndyke et al, 1985;Chapman et al, 1991;Moore et al, 1992Moore et al, , 1993 had shown R3327-AT tumours to exhibit both inter-and intratumour heterogeneity of blood flow and perfusion with an average radiobiological HF of -15%. The well-differentiated R3327-H tumour showed no evidence of significant HF by radiobiological and hypoxic marker assays (Thorndyke et al, 1985).…”

Section: Materials and Methods Hypoxic Markersmentioning

confidence: 97%

A dual hypoxic marker technique for measuring oxygenation change within individual tumors

Iyer

Kim²,

Schneider³

et al. 1998

Br J Cancer

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Summary Rodent tumour models have been the 'workhorse' for tumour oxygenation research and for investigating radiobiological hypoxic fraction. Because of the intertumour heterogeneity of blood flow and related parameters, most studies have pooled information derived from several different tumours to establish the statistical significance of specific measurements. But it is the oxygenation status of and its modulation in individual tumours that has important prognostic significance. In that regard, the bioreducible hypoxic marker technique was tested for its potential to quantify oxygenation changes within individual tumours. f-D-lodinated azomycin galactoside (IAZG) and P-Diodinated azomycin xylopyranoside (IAZXP) were each radiolabelled with lodine-125 and iodine-131 for measurements of animal tumour oxygenation. The tumour-blood (T/B) ratio of marker radioactivity in mice after the renal excretion of unbound marker (at 3 h and longer times) had been shown to be proportional to radiobiological hypoxic fraction. When markers labelled with both radioisotopes were administered simultaneously to EMT-6 tumour-bearing scid mice, T/B ratios were found to vary by up to 300% between different tumours, with an average intratumour variation of only -4%. When the markers were administered 2.5-3.0 h apart, changes in T/B ratios of 8-25% were observed in 10 out of 28 (36%) tumours. Changes to both higher and lower hypoxic fraction were observed, suggestive of acute or cycling hypoxia. When 0.8 mg g-1 nicotinamide plus carbogen was administered to increase tumour oxygenation, reductions in T/B ratios (mean AT/B -38%) were observed in all tumours. Similar results were obtained with Dunning rat prostate carcinomas growing in Fischer X Copenhagen rats whose T/B ratios of IAZG and radiobiological hypoxic fractions are significantly lower. These studies suggest that fluctuating hypoxia can account for at least 25% of the total hypoxic fraction in some tumours and that correlations between bioreducible marker avidity and related tumour properties will be optimal when the independent assays are performed over the same time period. This dual hypoxic marker technique should prove useful for investigating both spontaneous and induced oxygenation changes within individual rodent tumours.

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“…administration of 15 mg/kg Photofrii. 18 The tumor volumes treated in the first study16 were between 0.5-0.8 cm3 and those treated in the other study'8 were 2-3 cm3. Tumor response observed in these studies was by tumor perfusion shutdown and secondary ischemic tumor cell death.…”

Section: Discussionmentioning

confidence: 99%

Exploitation of interstitial brachytherapy techniques for photodynamic therapy--II. Novel photosensitizeers for the treatment of solid tumors

et al. 1994

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The treatment of solid human tumors of volume up to 50 cm3 will require significant gains in photosensitizing effect over that obtained with Photofrii and 630 nm light. Some techniques ofinterstitial radioisotope brachytherapy can be exploited for the uniform delivery oflaser light to solid tumor volumes. Our dosimetry planning system (T-PIPET) was used to design 7-and 9-fiber illuminators for the treatment of R3327AT rat prostate tumors by interstitial PDT. Relatively uniform light fields within encompassed tumor volumes could be achieved with needle spacings of 0.9 and 1.2 cm for light of 670 and 750 nm, respectively. Novel photosensitizers derived from pheophorbide and bacteriopheophorbide and activated by 673 and 753 nm light, respectively, were at least 1000X more potent than Photofrii i n photokilling EMT6 tumor cells in vitro. Tumor response in vivo resulted from perfusion shutdown and secondary ischemic cell death. Complete tumor reponse and some cures were demonstrated when R3327-AT rat prostate tumors of 3.5.4.5 cm" volume were treated with 400 J of 673 nm light delivered 1 hr after the i.v. administration of 2mg/kg Ph4-OH. Current studies will optimize the vehicle for drug delivery, the time between drug and light administration and the light dose uniformity required throughout a treatment volume for maximizing tumor cures. A two-fold gain in tissue penetrance by longer wavelength light combined with at least a 100X gain in in vivo efFectiveness by these novel photosensitizers makes feasible the treatment of solid human tumors by interstitial PDT with current laser systems.

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Non-invasive monitoring of photodynamic therapy with 99technetium HMPAO scintigraphy

Cited by 21 publications

References 14 publications

Measurement of Tumor Vascular Damage in Mice with 99m Tc‐MIBI Following Photodynamic Therapy

Measurement of Tumor Vascular Damage in Mice with 99m Tc‐MIBI Following Photodynamic Therapy

A dual hypoxic marker technique for measuring oxygenation change within individual tumors

Exploitation of interstitial brachytherapy techniques for photodynamic therapy--II. Novel photosensitizeers for the treatment of solid tumors

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